Dissertations / Theses: 'Central nervous systems'

1

Radke, James Melvin. "Studies involving somatostatin systems in the rodent central nervous system." Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/26518.

Full text

Abstract:

Somatostatin is a neuropeptide found throughout the brain. Several studies have established its anatomical distribution as being quite heterogenous with relatively high concentrations appearing in the limbic and striatal systems. Presently, very little is known about the functions of somatostatin systems in the brain and how they interact with other transmitter systems. The following report is a summary of experiments undertaken to assess the functional and chemical interactions of somatostatin with other neurotransmitter systems. Previous studies have established that the dopaminergic inputs to the basal ganglia are important for locomotor activity and reward. These systems have also been implicated in several mental and neural diseases such as schizophrenia, depression, and Parkinson’s disease. In the first experiment, interactions between dopamine and somatostatin systems were examined using paradigms involving behavioural responses to dopamine agonists. Depletion of somatostatin levels by the drug cysteamine was found to attenuate amphetamine- and apomorphine-mediated motor behaviours but not the reinforcing aspects of amphetamine. The second experiment attempted to further characterize the nature of the dopamine-somatostatin interaction by examining the effects of haloperidol, a dopamine antagonist, on central somatostatin levels. Short term treatment with haloperidol decreased striatal somatostatin levels. Long term treatment (8 months) with haloperidol failed to alter somatostatin levels in the caudate-putamen. Since somatostatin levels appear to be normal in Parkinsonian brains, the effects of MPTP poisoning in mice on central somatostatin levels was also studied to examine the accuracy of this animal model of Parkinson's disease and examine the effects of dopaminergic lesions on somatostatin levels. The results of this experiment indicate that MPTP causes a dose dependent increase in nigral somatostatin levels without altering striatal or cortical levels. These results are in partial disagreement with results obtained from both post-mortem Parkinsonian brains and primates given MPTP, thereby questioning the accuracy of this mouse model of Parkinson's disease. The final experiment examined the effects of the anticonvulsant-antidepressant carbamazepine on central somatostatin levels in the rat. Although the chemical mechanisms responsible for the therapeutic effects of carbamazepine are unknown, previous studies have suggested that its efficacy in the treatment of both manic-depression and epilepsy may be associated with the ability of this drug to reduce the abnormal somatostatin levels observed in these diseases. In this experiment, neither acute, chronic, nor withdrawal from chronic treatment with carbamazepine were found to alter the levels of somatostatin in rats. The lack of effects of carbamazepine on basal somatostatin levels may indicate somatostatin cells are susceptible to carbamazepine only under pathological situations. Together, these results are discussed in the context of recent observations of abnormal somatostatin levels in several diseases of the central nervous system and provide some insight into the interactions and functions of somatostatin systems in the normal and abnormal brain.
Medicine, Faculty of
Graduate

APA, Harvard, Vancouver, ISO, and other styles

2

Stumpf, da Silva Taisa Regina. "Delivery Systems to Enhance Neural Regeneration in the Central Nervous System." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39391.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Morgenstern, Daniel Alexander. "Chondroitin sulphate proteoglycans in the peripheral and central nervous systems." Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620931.

Full text

APA, Harvard, Vancouver, ISO, and other styles

4

Rubeo, Scott Edward. "Control of Simulated Cockroach Using Synthetic Nervous Systems." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1495555770825904.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Marsh, Barnaby C. L. "The Role of Osteopontin in the Peripheral and Central Nervous Systems." Thesis, University of Bristol, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486122.

Full text

Abstract:

The glycoprotein osteopontin (OPN) is a secreted and heavily phosphorylated peptide that plays a role in a variety of cellular processes from cell adhesion to apoptosis. These actions are principally thought to be mediated via interactions with CD44.and integrins. OPN is expressed in a wide variety of tissues including the peripheral and central nervous systems (PNS and CNS respectively), although its exact function in these tissues remains unclear. We identified OPN as a putative axotomy response gene from a previously generated dorsal root ganglia (DRG) subtractive cDNA library. Immunohistochemical ,staining demonstrated that OPN protein colocalises with neurofilament but not other nociceptive markers. Mechanosensory thresholds in osteopontin knockout (OPN KO) animals are significantly increased compared to wild-type (WT) controls, although there are no differences in allodynia between genotypes after a spared nerve injury (SNI) model of neuropathic pain. Moreover, exogenous recombinant OPN has no effect on neurite outgrowth from adult WT sensory neurons, and no differences in neurite outgrowth were observed in OPN KO animals compared to WT controls. Within the CNS, previous studies have demonstrated that OPN expression increases in a number of cell types after injury, although its precise function is equivocal. Here, I demonstrate that organotypic hippocampal OPN KO cultures display increased apoptosis following glutamate induced cell death compared to WT controls. Moreover, exogenous recombinant OPN is neuroprotective to OPN KO and WT cultures. This neuroprotective effect is integrin mediated and involves activation ofthe Akt and ERK pathways. In summary, these studies further extend our understanding of the neuroprotective and possible cell survival roles played by OPN in the nervous system. Further studies are now warranted to extend those presented here and define the mechanisms that underlie the observed effects thus far delineated.

APA, Harvard, Vancouver, ISO, and other styles

6

Jansson, Björn. "Models for the transfer of drugs from the nasal cavity to the central nervous system /." Uppsala : Acta Universitatis Upsaliensis: Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3905.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Shanbhag, Mihir S. Wheatley Margaret A. "Development of a multi-functional construct for central nervous system repair /." Philadelphia, Pa. : Drexel University, 2008. http://hdl.handle.net/1860/2906.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Gonçalves, Vanessa Santos Silva. "Overcoming Central Nervous System-barriers by the development of hybrid structured systems for nose-to-brain drug delivery using clean technologies." Doctoral thesis, Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica António Xavier, 2016. http://hdl.handle.net/10362/56395.

Full text

Abstract:

The effective delivery of therapeutics into the brain is challenging since drugs or drug delivery systems (DDS) candidates are not able to cross the blood-brain barrier (BBB), making the development of new drugs alone not enough to ensure progresses in Central Nervous System (CNS) drug therapy. Due to several problems related with other routes of brain drug administration, the interest has increased towards exploring the possibility of intranasal administration. The nose-to-brain transport and the therapeutic viability of this route have been investigated for rapid and effective transport of drugs to CNS, but the development of nasal drug products for brain targeting is still faced with many challenges.(...)
info:eu-repo/semantics/publishedVersion

APA, Harvard, Vancouver, ISO, and other styles

9

McClure-Sharp, Jilliane Mary, and mikewood@deakin edu au. "Regulation of corticotropin-releasing factor concentration and overflow in the rat central nervous system." Deakin University. School of Biological and Chemical Sciences, 1998. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20060802.143911.

Full text

Abstract:

Corticotropin-releasing factor (CRF) is the primary hormone of the hypothalamo-pituitary adrenal axis (HPA-axis). In addition to its endocrine function, it has been proposed that CRF acts as a neurotransmitter. The widespread distribution of CRF immunoreactivity and CRF receptors in the rat central nervous system (CNS) supports this theory. Immunohistochemical studies have demonstrated high levels of CRF immunoreactivity the rat hypothalamus, a brain region involved in the regulation and integration of a variety of endocrine and autonomic homeostatic mechanisms. CRF has been shown to be involved in a number of these activities such as blood pressure control, food and water intake, behaviour and emotional integration. Many of these activities demonstrate progressive dysfunction as ageing proceeds. The aim of this thesis was to investigate the regulation of CRF in the rat CNS, particularly over the period of maturation and ageing. Tissue extraction and peptide radioimmunoassay (RIA) techniques were developed in order to measure regional CRF concentrations as a function of age in the rat CNS. Seven brain regions were examined including the hypothalamus, pituitary, medulla oblongata, pons, cerebral cortex, cerebellum and midbrain. Three age ranges were investigated: 3 4 weeks, 4 5 months and 14 18 months, representing young, mature and old age groups. Data for the tissues of individual rats from each age group were analysed using one-way analysis of variance (ANOVA) with post-hoc Scheffé tests (SPSS Release 6 for Windows, 1989 1993). CRF were detected in measurable quantities in all brain regions examined. Different age-related patterns of change were observed in each brain region. CRF concentrations (ng/g tissue) were highest in the pituitaries of young rats and were significantly reduced over the period of maturation (P< 0.05). However, the high CRF concentration of the young rat pituitary was likely to be a factor of the smaller tissue mass. Although the absolute CRF content (ng/tissue) of this tissue appeared to decline with maturation and ageing, the reduction was not significant (P>0.05). Therefore the pituitary of the young rat was relatively enriched with CRF per gram tissue. The highest CRF concentration in mature and aged rats was measured in the hypothalamus, in accordance with previous immunohistochemical studies. Hypothalamic CRF concentrations (ng/g tissue) demonstrated no significant alterations with maturation and ageing. The absolute CRF content (ng/tissue) of the hypothalamus was significantly less in the young rat compared to mature and aged animals, however this was accompanied by a smaller tissue mass (P<0.05). The CRF concentrations (ng/g tissue) of the rat cerebral cortex and medulla oblongata demonstrated significant reduction with advancing age (P<0.05), however in both cases this appeared to be due to significant increases in mean tissue mass. The absolute CRF content of these tissues (ng/tissue) were not significantly different over the period of maturation and ageing (P>0.05). CRF concentration (ng/g tissue) and absolute content (ng/tissue) of the pons demonstrated a trend to increase with advanced age in the rat, however this was not significant in both cases (P>0.05). Of interest were the significant increases observed in the CRF concentrations of the cerebellum and midbrain (ng/g tissue with advanced ageing (P<0.05). Significant increases were also observed in the mean tissue mass and absolute CRF content (ng/tissue) of these regions in aged rats (P<0.05). These findings perhaps indicate increased CRF synthesis and or decreased CRF turnover in these tissues with advancing age. The second stage of these studies examined age-related alterations in basal and potassium-stimulated hypothalamic CRF and overflow over the period of maturation and ageing in the rat, and required the preliminary development of an in vitro tissue superfusion system. The concomitant release of the co-modulatory compound, neuropeptide Y (NPY) was also measured. NPY has been shown to positively regulate CRF release and gene expression in the hypothalamus. In addition, NPY has been demonstrated to be involved in a number of hypothalamic activities, including blood pressure control and food intake regulation. Hypothalamic superfusion data were analysed using one factor repeated measures ANOVA (SPSS Release 6 for Windows, 1989-1993) followed by least significant difference tests ( Snedecor and Cochran, 1967) to enable both time and age comparisons. Basal hypothalamic CRF overflow was unaltered with maturation and ageing in the rat. Potassium stimulation (56 mM) elicted a significant 2 3 fold increase in hypothalamic CRF overflow across age groups (P<0.05). Stimulated hypothalamic CRF overflow was significantly greater in the young rat compared to the mature and aged animals (P<0.05). The enhanced response to depolarizing stimulus was observed at an age when the absolute CRF content of the hypothalamus was significantly less that of other age groups. It is possible that the enhanced responsiveness of the young rat may be of survival advantage in life threatening situations. Basal hypothalamic NPY overflow was much less than that of CRF, and potassium stimulation resulted in a very different age-related profile. The hypothalamic NPY response to depolarization was significantly reduced in the young rat and declined significantly with advanced ageing (P<0.05). The contrasting profiles of stimulated CRF and NPY overflow may indicate the activity of alternative regulatory factors present in the hypothalamus, whose activity may also be affected in an age-related manner. The final stage of these studies examined the nature of NPY modulation of hypothalamic CRF overflow in the mature rat. The facilitatory effect of NPY on hypothalamic CRF overflow was confirmed. The application of NPY (0.1 µM) significantly increased CRF overflow approximately 4 fold of basal (P<0.05). In addition, the role of the NPY-Y1 receptor was investigated by the prior application of Y1 receptor antagonists, GW1229 (0.05 µM). At this concentration GW1229 significantly reduced hypothalamic CRF overflow induced by perfusion with NPY (0.1 µm), P<0.05. It was concluded the Y1 receptor does have a role in the regulation of hypothalamic CRF overflow by NPY.

APA, Harvard, Vancouver, ISO, and other styles

10

Passaro, Peter A. "Multi-electrode array recording and data analysis methods for molluscan central nervous systems." Thesis, University of Sussex, 2012. http://sro.sussex.ac.uk/id/eprint/43341/.

Full text

Abstract:

In this work the use of the central nervous system (CNS) of the aquatic snail Lymnaea stagnalis on planar multi-electrode arrays (MEAs) was developed and analysis methods for the data generated were created. A variety of different combinations of configurations of tissue from the Lymnaea CNS were explored to determine the signal characteristics that could be recorded by sixty channel MEAs. In particular, the suitability of the semi-intact system consisting of the lips, oesophagus, CNS, and associated nerve connectives was developed for use on the planar MEA. The recording target area of the dorsal surface of the buccal ganglia was selected as being the most promising for study and recordings of its component cells during fictive feeding behaviour stimulated by sucrose were made. The data produced by this type of experimentation is very high volume and so its analysis required the development of a custom set of software tools. The goal of this tool set is to find the signal from individual neurons in the data streams of the electrodes of a planar MEA, to estimate their position, and then to predict their causal connectivity. To produce such an analysis techniques for noise filtration, neural spike detection, and group detection of bursts of spikes were created to pre-process electrode data streams. The Kohonen self-organising map (SOM) algorithm was adapted for the purpose of separating detected spikes into data streams representing the spike output of individual cells found in the target system. A significant addition to SOM algorithm was developed by the concurrent use of triangulation methods based on current source density analysis to predict the position of individual cells based on their spike output on more than one electrode. The likely functional connectivity of individual neurons identified by the SOM technique were analysed through the use of a statistical causality method known as Granger causality/causal connectivity. This technique was used to produce a map of the likely connectivity between neural sources.

APA, Harvard, Vancouver, ISO, and other styles

11

Mounger, David Kyle, Kynlee Hillard, Brooke Tipton, Grayson D. White, and Matthew R. Zahner. "GLP-1 agonist liraglutide increases metabolic- and cardiovascular-related sympathetic activity of the central nervous system." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/58.

Full text

Abstract:

Metabolic syndrome is associated with pathologies that include type 2 diabetes, hypertension, and dyslipidemia, all of which increase the risks of heart disease. Glucagon-like peptide (GLP-1) is a hormone produced by intestinal enteroendocrine L‑cells. GLP-1 increases insulin sensitivity, augments glucose-dependent insulin secretion, and suppresses glucagon release. GLP-1 also works centrally to decrease appetite and increase metabolism. Evidence suggests that the beneficial effect is mediated by metabolically related sympathetic neurons within the hypothalamus. Although the hypothalamus contains neurons that control metabolism, there are also neurons that control cardiovascular activity. Considering that one main goal of obesity and diabetes treatments is to reduce cardiovascular-related comorbidities, any drug‑induced increase in blood pressure is unacceptable. Therefore, a better understanding of GLP-1 agonists on sympathetic activity and the role of the hypothalamus in central GLP‑1 activity is essential. In this study, we tested the hypothesis that the long‑acting FDA approved GLP-1 receptor agonist liraglutide activates both metabolic and cardiovascular‑related hypothalamic neurons and augments reflex cardiovascular sympathetic activity in rats. To test this hypothesis, we administered liraglutide (125 mg/kg, SC, n=10) or vehicle (saline, n=10) to rats for 15 days and measured food intake and body weight. Next, we recorded blood pressure and renal sympathetic nerve activity (RSNA) in the anesthetized rat before and after liraglutide treatment. Finally, to determine the activation of hypothalamic neurons we performed neuroanatomical tracing studies and turned metabolically-related (raphe‑projecting) neurons green, and cardiovascular-related (rostroventrolateral medulla, RVLM) neurons red. After treating rats with liraglutide, (75 mg/kg IV) we performed immunohistochemical (IHC) labeling to identify neurons expressing cFos, a marker of neuronal activation. Daily liraglutide significantly (p < 0.05) reduced both food intake and body weight from the pretreatment baseline. In vehicle-treated rats, the mean baseline food intake was 27.9 ± 0.5g. During vehicle treatment, the mean food intake was 28.6 ± 0.8 g and body weight was 110 ± 1.5% of its baseline. In liraglutide-treated rats, the mean baseline food intake was 29.9 ± 0.7g. During liraglutide treatment, the mean food intake was 22.7 ± 1.4g and body weight was 105 ± 1.1% of its baseline. At the end of liraglutide treatment, food intake and body weight returned to that of the vehicle-treated rats. In the anesthetized rat, liraglutide significantly (p < 0.05) increased basal RSNA and augmented baroreflex and chemoreflex activity. Lastly, our cFos data show that liraglutide activates metabolic, but not cardiovascular hypothalamic neurons. Collectively, these data suggest that although liraglutide elevates sympathetic activity, it is not by activation of pre-sympathetic hypothalamic neurons.

APA, Harvard, Vancouver, ISO, and other styles

12

Martel, Jean-Claude. "Autoradiographic and pharmacological studies of neuropeptide Y receptors in central and peripheral nervous systems." Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74569.

Full text

Abstract:

The distribution of neuropeptide Y (NPY) receptor sites was investigated in certain mammalian species using receptor autoradiography and membrane binding assay techniques. NPY receptor sites are discretely distributed throughout the central nervous systems of hamster, rat, guinea pig and monkey but are particularly concentrated in cortex and hippocampus. NPY receptor autoradiography techniques also revealed important labelling of numerous thalamic nuclei while most hypothalamic nuclei showed surprisingly low densities of NPY receptor sites, considering the high levels of NPY-like immunoreactivity in this brain area. The widespread distribution of NPY receptor sites suggests that this peptidergic system must have important roles in mammalian central nervous system. In particular, the possible involvement of NPY in cognitive function deserves further investigation since we observed that ($ sp3$H) NPY receptor site densities are decreased in temporal cortex and hippocampus of individuals decreased with Alzheimer's disease.
The possible existence of NPY/peptide YY (PYY) receptor subtypes was investigated in the rat brain. Overall, the similar autoradiographic distribution of ($ sp{125}$I) BH-NPY and ($ sp{125}$I) PYY in most areas suggests that these two receptor probes most likely interact with the same population of NPY/PYY receptor sites. ($ sp{125}$I) PYY may recognize both a high and low affinity state/subtype of NPY/PYY receptors while ($ sp{125}$I) BH-NPY recognize a single affinity state of receptor having the binding characteristics of the low affinity ($ sp{125}$I) PYY receptor state/subtype. The exact nature of this high affinity receptor state/subtype remains to be established.
Finally, the structural requirements of NPY receptors in central (CNS) and peripheral (PNS) nervous systems were also examined with a binding assay on rat brain membrane preparation and with the rat vas deferens bioassay preparation. The amino acid residues responsible for the activation of NPY receptors in the rat vas deferens preparation lie in the C-terminal half of the NPY molecule as revealed by the loss of potency, but not of biological activity with C-terminal fragments up to NPY$ sb{18-36}$. The N-terminal portion of the NPY molecule appears to be mostly important to insure adequate affinity for central and peripheral NPY receptors. Moreover, a series of NPY analogs revealed that the two tyrosine residues in position 20 and 21 are not directly involved in NPY receptor activation in this bioassay preparation, although they appear relatively important for the maintenance of adequate affinity for the receptors. Interestingly, modifications of the tyrosine residue in position 20 led to the development of two analogs demonstrating a certain degree of selectivity for the PNS receptors while other modifications of tyrosine residues in position 21 may provide some selectivity for CNS receptor sites. (Abstract shortened by UMI.)

APA, Harvard, Vancouver, ISO, and other styles

13

Laguna, Tuset Ariadna. "Study of Dyrk1a kinase in central nervous systems development: implication in mouse retina development." Doctoral thesis, Universitat Pompeu Fabra, 2008. http://hdl.handle.net/10803/7115.

Full text

Abstract:

El gen DYRK1A es troba situat en una regió del cromosoma 21 humà que s'ha associat a alteracions en el neurodesenvolupament. Aquest treball mostra com canvis en la dosis gènica de Dyrk1A en el ratolí causen una alteració en la cel.lularitat de les capes internes de la retina i provoquen alteracions funcionals severes. A més a més, la sobreexpressió de Dyrk1A és la única responsable de les alteracions en la retina dels animals Ts65Dn, un model murí de Síndrome de Down. El control de la mort cel.lular programada és fonamental pel correcte desenvolupament del sistema nerviós central. Aquest treball demostra que la proteïna quinasa DYRK1A és un regulador negatiu de la via intrínseca d'apoptosis durant el desenvolupament de la retina. DYRK1A no afecta la proliferació o especificació de les cèl.lules progenitores, sinó que regula el nombre de cèl.lules que moren per apoptosis. La caspasa-9 és un nou substracte de DYRK1A, i la fosforilació de la caspasa al residu treonina 125 per DYRK1A protegeix les cèl.lules de la retina de la mort apoptòtica. Aquestes dades suggereixen un model en el qual una desregulació de la resposta apoptòtica en neurones en diferenciació podria participar en la neuropatologia de malalties que pesenten una alteració en la dosis gènica de DYRK1A.
DYRK1A is located in a region of human chromosome 21 (HSA21) that has been associated to the neurodevelopmental impairments shown by individuals with HSA21 aneuploidies. This work shows changes in Dyrk1A gene dosage in the mouse strongly alter the cellularity in inner retina layers and results in severe functional alterations. Moreover, overexpression of Dyrk1A is solely responsible for the retina alterations shown by Ts65Dn mice, a mouse model for Down syndrome. The precise regulation of programmed cell death is critical for the normal development of the nervous system. This work demonstrates that DYRK1A protein kinase is a negative regulator of the intrinsic apoptotic pathway in the developing retina. DYRK1A does not affect the proliferation or specification of retina progenitor cells, but rather regulates the number of cells that die by apoptosis. Caspase-9 is a novel DYRK1A substrate, and the phosphorylation on caspase-9 at threonine residue 125 by DYRK1A protects retina cells from apoptotic cell death. This data suggests a model in which dysregulation of the apoptotic response in differentiating neurons participates in the neuropathology of diseases that display DYRK1A gene dosage imbalance effects.

APA, Harvard, Vancouver, ISO, and other styles

14

Smith, Jacqueline Anne McInnes. "Characterisation of kappa opioid receptors in the guinea-pig and rat central nervous systems." Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333423.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Sandberg, Arne. "Dynamic Changes in the Peripheral and the Central Nervous Systems in Patients with Prior Polio." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4617.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Tigerholm, Jenny. "Mechanisms of excitability in the central and peripheral nervous systems : Implications for epilepsy and chronic pain." Doctoral thesis, KTH, Beräkningsbiologi, CB, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-93496.

Full text

Abstract:

The work in this thesis concerns mechanisms of excitability of neurons. Specifically, it deals with how neurons respond to input, and how their response is controlled by ion channels and other active components of the neuron. I have studied excitability in two systems of the nervous system, the hippocampus which is responsible for memory and spatial navigation, and the peripheral C–fibre which is responsible for sensing and conducting sensory information to the spinal cord. Within the work, I have studied the role of excitability mechanisms in normal function and in pathological conditions. For hippocampus the normal function includes changes in excitability linked to learning and memory. However, it also is intimately linked to pathological increases in excitability observed in epilepsy. In C–fibres, excitability controls sensitivity to responses to stimuli. When this response becomes enhanced, this can lead to pain. I have used computational modelling as a tool for studying hyperexcitability in neurons in the central nervous system in order to address mechanisms of epileptogenesis. Epilepsy is a brain disorder in which a subject has repeated seizures (convulsions) over time. Seizures are characterized by increased and highly synchronized neural activity. Therefore, mechanisms that regulate synchronized neural activity are crucial for the understanding of epileptogenesis. Such mechanisms must differentiate between synchronized and semi synchronized synaptic input. The candidate I propose for such a mechanism is the fast outward current generated by the A-type potassium channel (KA). Additionally, I have studied the propagation of action potentials in peripheral axons, denoted C–fibres. These C–fibres mediate information about harmful peripheral stimuli from limbs and organs to the central nervous system and are thereby linked to pathological pain. If a C–fibre is activated repeatedly, the excitability is altered and the mechanisms for this alteration are unknown. By computational modelling, I have proposed mechanisms which can explain this alteration in excitability. In summary, in my work I have studied roles of particular ion channels in excitability related to functions in the nervous system. Using computational modelling, I have been able to relate specific properties of ion channels to functions of the nervous system such as sensing and learning, and in particular studied the implications of mechanisms of excitability changes in diseases.

QC 20102423

APA, Harvard, Vancouver, ISO, and other styles

17

Geiselbrecht, Hannes [Verfasser], and Roland [Akademischer Betreuer] Melzer. "Morphology and evolution of Malacostraca : structure of central nervous systems, mandibles and sensilla / Hannes Geiselbrecht. Betreuer: Roland Melzer." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2014. http://d-nb.info/1056876670/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Ferri, Catharine C. "The role of the p75 low-affinity neurotrophin receptor in the peripheral and central nervous systems following nerve injury." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ31203.pdf.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Rosin, Åsa. "Effects of joint cocaine and ethanol on the brain opioid systems /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-441-4/.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Birgner, Carolina. "Anabolic androgenic steroids and central monoaminergic systems : Supratherapeutic doses of nandrolone decanoate affect dopamine and serotonin." Doctoral thesis, Uppsala University, Department of Pharmaceutical Biosciences, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9208.

Full text

Abstract:

Supratherapeutic doses of anabolic androgenic steroids (AASs) are administered, not only as performance-enhancing drugs in the world of sports, but also in order to modify behaviour. AAS abusers are at risk of developing serious physical and psychological side effects such as dependence and aggressive behaviour. The aim of this thesis was to investigate the impact of supratherapeutic doses of nandrolone decanoate after subchronic administration on dopamine and serotonin pathways involved in drug dependence and aggression, in the male rat brain.

Adult male Sprague-Dawley rats received intramuscular injections of nandrolone decanoate (3 or 15 mg/kg) or vehicle once daily for 14 days. Nandrolone decanoate pre-exposure abolished the effect of amphetamine on the 3,4-dihydroxyphenylacetic acid (DOPAC) tissue level in the hypothalamus and on the DOPAC/dopamine ratio in the hypothalamus and the hippocampus. A significant decrease of the basal extracellular DOPAC and homovanillic acid (HVA) levels could be detected in the nucleus accumbens, which remained low during the first hour following the amphetamine challenge. Nandrolone decanoate significantly reduced the activity of both monoamine oxidase A and B (MAO-A and -B) in the caudate putamen and amygdala. The gene transcript levels of MAO-B, and the dopamine D1 and D4 receptors were altered in limbic regions. No changes in transcriptional levels could be detected among the serotonin receptor genes examined. However, the density of the serotonin transporter protein was elevated in a range of aggression-related brain regions.

Taken together, subchronic administration of nandrolone decanoate causes dopaminergic and serotonergic dysregulations in distinct brain regions. These areas of the brain are involved in the development of drug dependence and expression of impulsive and aggressive behaviours. These results may contribute to explain some of the behavioural changes often reported in AAS abusers, such as polydrug use and impaired impulse control.

APA, Harvard, Vancouver, ISO, and other styles

21

Ye, Ping. "The regulation of 11-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat central nervous and cardiovascular systems." Thesis, University of Glasgow, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414120.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Doenlen, Raphael Aloise. "Fingerprints of neural activity after peripheral immune challenges : an experimental study on the communication between the immune and central nervous systems /." [S.l.] : [s.n.], 2008. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=18084.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Spaw, Alexandra J. "Fetal Developmental Anatomy of the Human Cardiovascular and Central Nervous Systems Using Lugol’s Iodine Staining and Micro-Computed Tomography." Ohio University Honors Tutorial College / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1398950897.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Chaves, Hernández Aida Jeannette. "Study of the pathogenesis of highly pathogenic influenza A virus (H7N1) infection in chickens, with special focus in the central nervous system." Doctoral thesis, Universitat Autònoma de Barcelona, 2011. http://hdl.handle.net/10803/83958.

Full text

Abstract:

Los virus de influenza aviar de alta patogenicidad (IAAP) causan una enfermedad muy severa en pollos, los cuales frecuentemente inducen lesiones en el sistema nervioso central (SNC). Esta tesis recoge los resultados de tres estudios que se llevaron a cabo para determinar el mecanismo de patogénesis y neurotropismo, así como establecer la ruta de entrada al SNC para un virus H7N1 IAAP. En el primer estudio se estableció un modelo animal de infección en pollos libres de patógenos específicos, que consistía en la inoculación intranasal con el virus H7N1 IAAP. Para establecer este modelo, se utilizaron tres diferentes dosis del virus, obteniendo que las dosis más altas producen una enfermedad similar a la reportada para otros virus de IAAP. Además, se observó que las dosis más bajas causan infección demostrada porque con las dosis más bajas, el virus es hallado en muestras de tejido, muestras de heces y secreciones respiratorias. Adicionalmente, se pudo comprobar el alto neurotropismo del virus, ya que aún en pollos inoculados con bajas dosis el RNA viral es hallado en el CNS. La viremia fue detectada a un día post infección (dpi), sugiriendo que está podría ser la vía de diseminación al SNC. En el segundo estudio, se determinó la distribución topográfica del antígeno viral en el SNC durante las primeras horas post infección, lo cual permitió determinar que el virus se disemina de forma simétrica y bilateral en núcleos neurales del diencéfalo, mesencéfalo y rombencéfalo. La distribución del antígeno viral indica que el bulbo olfatorio y los nervios periféricos están involucrados en el proceso de invasión del SNC. El hallazgo de receptores aviares y humanos en las células endoteliales explica porque estas células son tan sensibles a la infección. El RNA viral fue hallado en el líquido cerebro espinal el primer dpi, lo que indica que el virus atraviesa la barrera hemato-encefálica (BHE). En el tercer estudio, la alteración de la BHE inducido por el virus H7N1 IAAP fue demostrado usando tres diferentes métodos que incluye la perfusión intracardial de Azul de Evans, la detección de la extravasación de la proteína del suero IgY, y evaluación del patrón de tinción con el marcador de las uniones fuertes de la BHE, ZO-1 y claudin-1. El antígeno viral fue observado a las 24 hpi en las células endoteliales, mientras que el daño de la BHE fue observado a las 36 hpi y 48 hpi. En resumen, se puede afirmar que el virus H7N1 IAAP se disemina por la vía hematógena durante las primeras horas pi, posiblemente favorecido por la presencia de receptores en las células endoteliales del sistema nervioso central, y poco después daña la BHE durante las primeras horas de infección como se demuestra por la presencia de extravasación del azul de Evans and IgY del suero.
Highly pathogenic avian influenza viruses (HPAIV) cause a very severe systemic disease in chickens, in which is also frequent to find central nervous system (CNS) lesions. In this thesis, three studies were undertaken in order to determine the mechanism of pathogenesis, the neurotropism and establish the route of entry into the CNS use for a H7N1 HPAI virus. In the first study, an animal model was set up that consisted of SPF chickens inoculated intranasally with the H7N1 HPAI virus. To do that, three different doses were used, obtaining that the highest dose induced a disease similar to the produce by other HPAI viruses, moreover, it was also observed that very low doses also cause infection demonstrated because viral RNA was found in tissues samples, faeces and respiratory secretions. Besides, the high neurotropism of this virus was demonstrated because still in chickens inoculated with low doses, viral RNA is found in the brain. Viremia was detected at one dpi, which indicated that the bloodstream is the pathway of viral spreading to the brain. In the second study, the topographical distribution study of the viral antigen during the first dpi was determined, which allow to determine that the virus disseminates showing a symmetrical and bilateral pattern in the diencephalon, mesencephalon and rhombencephalon, whereas in the telencephalon and cerebellum it was multifocal and random. Viral antigen distribution indicates that the olfactory bulb (OB) and peripheral nerves are not involved in the process of virus invasion into the brain. Avian and human influenza receptors were found in endothelial cells which explain why these cells are so sensitive to the infection. Viral RNA was found in cerebrospinal fluid (CSF) at one dpi, indicating that the virus was able to cross blood brain barrier (BBB). In the third study, the disruption of the BBB induce by the H7N1 HPAI was demonstrated using three different methods that include the intracardial perfusion of the tracer Evans blue (EB), detection of the extravasation serum IgY, and evaluation of the pattern of staining of the tight junction proteins ZO-1 and claudin-1. Viral antigen can be observed as early as 24 hpi in the endothelial cells, whereas disruption was detected at 36 and 48 hpi. In summary, it can be asserted that this H7N1 HPAIV disseminates via the haematogenous route early during the infection, favored by the presence of abundant receptors on the CNS endothelial cells, and soon after it disrupts the BBB during the first hours of infection as demonstrated by the presence of EB and serum IgY extravasation.

APA, Harvard, Vancouver, ISO, and other styles

25

Bland-Ward, Philip Antony. "Inhibition of nitric oxide synthase by indazole derivatives : an evaluation of the pharmacological effects of 7-nitro indazole in the cariovascular and central nervous systems." Thesis, King's College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363010.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Henry, Axelle. "Vectorisation cérébrale de deux radiotraceurs d’intérêts pour l’imagerie, la m-iodobenzylguanidine (MIBG) et la 3’-désoxy-3’- fluoro-L-thymidine (FLT)." Thesis, Rouen, INSA, 2016. http://www.theses.fr/2016ISAM0019.

Full text

Abstract:

Ce travail de recherche s'intéresse à la vectorisation au système nerveux central de la MIBG d'une part et de la FLT d'autre part. Pour cela, nous utiliserons des systèmes disposant d'une structure 1,4- dihydoquinoléine comme vecteurs. La synthèse des systèmes de vectorisation a tout d'abord été réalisée en chimie non radioactive. Concernant la MIBG, les résultats obtenus lors de précédents travaux nous ont conduit à envisager l'élaboration d'un système de vectorisation comportant un groupement espaceur entre le vecteur et la MIBG. Dans le cas de la FLT, nous nous sommes consacrés au développement d'un système dans lequel la FLT serait directement liée au vecteur par une liaison ester. Afin de pouvoir moduler les propriétés rédox de nos systèmes de vectorisation, nous avons synthétisé des 1,4-dihydroquinoléines présentant en position 6 et/ou 7 des groupements électroattracteurs ou électrodonneurs. Une étude en milieu acétonitrile/tampon PBS, pour évaluer l'influence de ces groupements sur la libération de la FLT, a été réalisée par un suivi CLHP. La radiosynthèse de ces systèmes a ensuite été menée afin d'évaluer la capacité des vecteurs 1,4- dihydroquinoléines à transporter la MIBG ou la FLT à travers la barrière hématoencéphalique (BHE). Ainsi, nous avons radiomarqué au carbone-11 les systèmes de vectorisation pour valider le passage de la BHE. Des études ex vivo chez le petit animal ont permis de suivre la pénétration cérébrale ainsi que la cinétique d'oxydation au niveau cérébral et en périphérie
This research work focuses on targeting MIBG or FLT to the central nervous system. The synthesis of 1,4-dihydroquinoline carriers was first carried out in a non-radioactive manner. Previous results led us to consider the use of a linker to connect MIBG to the carrier. Regarding FLT, we focused our interest in the development of a carrier system connected directly to FLT via an ester function. For modulating the redox properties of our delivery systems, we synthesized 1,4-dihydroquinolines having electron-donating or electron-withdrawing groups at position 6 and/or 7. A study in acetonitrile/PBS buffer to determine the influence of these groups on the release of FLT was performed by HPLC. The radiosynthesis of these targeting systems was then conducted to evaluate the ability of 1,4- dihydroquinolines to deliver MIBG or FLT across the blood brain barrier (BBB). Thus, using carbon-11, we radiolabeled the delivery systems to validate the BBB crossing. Small animais were used for ex vivo studies to monitor the brain penetration and the kinetics of oxidation in the brain and periphery

APA, Harvard, Vancouver, ISO, and other styles

27

Johansson, Jenny. "The Impact of Growth Hormone and Gamma-Hydroxybutyrate (GHB) on Systems Related to Cognition." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-185631.

Full text

Abstract:

Drug dependence is a serious and increasing problem in our society, especially among adolescents. The use of the large variety of substances available can result in a range of physiological and psychological adverse effects on individuals and negative consequences on the society overall. Several different types of drugs induce neurotoxicological damages, which in turn can generate impairment in for example the reward system and affect cognitive parameters. The drug gamma-hydroxybutyrate (GHB) is usually considered a harmless compound among abusers, but has now shown to be highly addictive. Furthermore, GHB can cause memory impairments in both humans and animals. On the contrary, growth hormone (GH) and its main mediator insulin-like growth factor 1 (IGF-1) have recently been suggested to improve memory and learning in several studies. The hormones exhibit certain neuroprotective capabilities and have also previously been demonstrated to reverse opioid induced apoptosis in hippocampal cells. These effects and the fact that GHB is shown to increase GH secretion, which attracted considerable attention among body builders, led us to initiate studies on GHB and its impact on relevant systems in the central nervous system (CNS). Thus, the main purpose of the present investigation was to elucidate some of the underlying mechanisms that could account for the effects exerted by GH and GHB in the CNS. We found that a) GH affects the density and functionality of GABAB-receptors and opioid receptors in the male rat brain, b) GHB induces cognitive deficits and down-regulates GABAB-receptors, c) GHB treatment creates an imbalance between the endogenous opioids Met-enkaphalin-Arg6Phe7 (MEAP) and dynorphin B and increases the levels of MEAP in regions of the brain that are associated with drug dependence, and d) GHB affects the expression of IGF-1 receptors but not the plasma levels of IGF-1. In conclusion, the present work demonstrates that GH interacts with both opioid and GABAB-receptors in the male rat CNS and that GHB has an impact on brain regions associated with cognition and the development of dependence. These observations may be of relevance in many aspects related to addiction and might be translated into humans.

APA, Harvard, Vancouver, ISO, and other styles

28

Lothian, Carina. "Nestin regulation in the embryonic and adult CNS /." Stockholm : [Karolinska institutets bibl.], 2001. http://diss.kib.ki.se/2001/91-7349-057-1/.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

周韋基 and Wai-kei Dominic Chau. "A morphometric study of axon-glial interactions." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1995. http://hub.hku.hk/bib/B31212141.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Chau, Wai-kei Dominic. "A morphometric study of axon-glial interactions /." [Hong Kong] : University of Hong Kong, 1995. http://sunzi.lib.hku.hk/hkuto/record.jsp?B14801486.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Kopp, Jutta Maria. "Expression, regulation and functional aspects of the NPY Y1 receptors in rat /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4776-7/.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Zhang, Xiaochun. "Involvement of neuroinflammation in models of neurodegeneration." Laramie, Wyo. : University of Wyoming, 2008. http://proquest.umi.com/pqdweb?did=1663059561&sid=3&Fmt=2&clientId=18949&RQT=309&VName=PQD.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Mallah, Khalil. "In depth systemic biology analysis of central nervous system injuries." Thesis, Lille 1, 2018. http://www.theses.fr/2018LIL1S108/document.

Full text

Abstract:

Dans un contexte d’étude des altérations biologiques survenant après un impact sur le système nerveux central (SNC), ma thèse porte sur l’étude des modifications protéomiques et lipidiques survenant après une lésion du SNC. Une étude spatio-temporelle a été menée sur un modèle TBI de rat afin d'identifier des marqueurs spécifiques de la lésion. En utilisant le MALDI-MSI, nous avons effectués une reconstruction 3D du cerveau lésé 3 jours post-lésion et nous avons représentés les molécules lipidiques spécifiques à la lésion. Après, cette analyse est réalisé avec d’autres délais après l’impact: 1, 3, 7 et 10 jours. En parallèle, une analyse microprotéomique est réalisée sur des coupes de tissus dans une approche visant à corréler les modifications lipidiques et protéiques. Nos résultats ont permis d'identifier une famille de lipides, les acylcarnitines, exprimés dans le cortex lésé avec une intensité maximale à 3 jours post-impact. Les données de protéomiques ont montrés une régulation positive de l’expression de protéines liées à la maladie de Parkinson. Dans l’ensemble, nos résultats décrivent un lien entre le TBI léger et la maladie de Parkinson dès 3 jours après l’impact, avec un rôle possible de l’acylcarnitine. Cette même famille de molécules est aussi présente dans les lésions médullaires. Dans une approche thérapeutique, les résultats précédents ont montrés que la protéine RhoA est un candidat majeur dans SCI. Après avoir utilisé un inhibiteur de RhoA, une étude protéomique a été réalisée pour évaluer l’impact sur ces lésions. Les résultats montrent que les traitements in-vivo et in-vitro avec l’inhibiteur stimule la croissance neuritique et la régénération axonale
In the context of studying biological alterations occurring post impact to the central nervous system, my thesis was focused on studying the proteomic and lipid changes occurring post injury to the brain and spinal cord. A fundamental spatio-temporal study was conducted on an open-head rat TBI model to identify potential injury-specific markers. Using MALDI MSI, we performed 3D reconstruction of the injured brain at 3 days after injury and depicted lesion-specific m/z lipid molecules. After, MALDI MSI was applied on the acute/sub-acute time frame post impact: 1 day, 3 days, 7 days, and 10 days. In parallel, a microproteomic analysis was carried out on tissue segments directly consecutive to the imaged ones in an approach to correlate both lipid and protein changes. Our results yielded the identification of a family of lipids, acylcarnitines, which are expressed within the injured cortex with maximum intensity 3 days post impact. These lipid molecules also were found to be expressed in the substantia nigra and microproteomics data showed an upregulation in expression of Parkinson’s related proteins. Taken altogether, our results depict a role of link between mild-TBI and Parkinson’s disease as early as 3 days post impact, with a possible role of acylcarnitine. This same family of molecules was also present in SCI. In a therapeutic approach previous results showed RhoA protein as a major candidate post impact in SCI. After using RhoA inhibitor treatment, a proteomic study was carried out to investigate its impact on SCI. The results showed that both in-vivo and in-vitro treatment with RhoA inhibitor stimulated neurite outgrowth and helped in axonal regeneration

APA, Harvard, Vancouver, ISO, and other styles

34

Ng, Tat-fong. "Molecular basis for regeneration of CNS : a possible regulatory role of growth associated protein-43 /." Hong Kong : University of Hong Kong, 1995. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17538786.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Solomon, Thomas. "Central nervous system infections in Vietnam." Thesis, Open University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340736.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Zhang, Hui. "Remyelination in the central nervous system." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8095.

Full text

Abstract:

Multiple Sclerosis (MS) is an inflammatory disease which causes areas of demyelination in the Central Nervous System (CNS) and affects only humans. Current therapies for MS are focused on anti-inflammatory treatment, which reduce the occurrence and clinical relapses of the disease. However, progressive disability of the disease is related to axonal degeneration. After demyelination, remyelination occurs, which helps repair the demyelinated lesions and protects axons from degeneration. However, this endogenous remyelination is inefficient, and currently there are no therapies available to enhance remyelination. The aim of this thesis was to first characterize a fast and reliable model to study CNS remyelination in vitro, and second to investigate the role of semaphorin 3a (Sema3A) and semaphorin 3f (Sema3F) signaling in CNS remyelination. Various in vivo models have been developed to investigate the pathology of multiple sclerosis, and can be used to test remyelination therapies. However, in vivo models are expensive, animal- and time- consuming. Until now, there has been no well-characterized and robust in vitro model for remyelination study. In this thesis, an ex vivo slice culture system with mouse brain and spinal cord was developed, and characterized by immunofluorescent microscopy and transmission electron microscopy, for CNS remyelination study. Automated (re)myelinating quantification by image pro plus software was developed and validated to provide a fast and reliable way for testing factors that change remyelination efficiency. Two such factors are Sema3A and 3F, which were initially identified as axon guidance cues during development. Sema3A (repulsive) and 3F (attractive) were proved to play a role in oligodendrocyte precursor cell (OPC) migration during development, and hypothesized to be important in remyelination. In this thesis, I investigated the effects and mechanisms for this by adding recombinant SEMA3A or SEMA3F or by knockdown their obligatory receptors Neuropilin (Nrp) 1 and 2, using lentivirus induced miRNAi. Slice culture and primary OPC culture were used to determine the effect on OPC survival, migration, proliferation, differentiation and myelination.

APA, Harvard, Vancouver, ISO, and other styles

37

Grano, Fernanda Grecco. "Investigação do perfil de expressão gênica de receptores tipo toll e citocinas inflamatórias no encéfalo e no baço de cães com leishmaniose visceral /." Araçatuba, 2017. http://hdl.handle.net/11449/151332.

Full text

Abstract:

Orientador: Gisele Fabrino Machado
Banca: Valéria Marçal Felix de Lima
Banca: Flávia Lombardi Lopes
Banca: Paulo Ricardo Dell'Amerina Rocha
Banca: Monica Regina Vendrame Amarante
Resumo: A leishmaniose visceral (LV) é uma doença parasitária que apresenta distribuição mundial e que pode afetar homens e animais, sendo que o cão é considerado o principal hospedeiro da doença. Cães infectados pelo parasito Leishmania podem apresentar-se assintomáticos ou com desordens generalizadas, incluindo alterações neurológicas. Existem alguns relatos do acometimento do encéfalo durante a infecção, mas a neuropatogenia da doença não foi completamente elucidada. Há evidências do comprometimento das barreiras encefálicas e da presença do DNA do parasito no encéfalo. Os receptores tipo Toll (TLRs) são sensores do sistema imune inato capazes de detectar padrões moleculares associados aos patógenos (PAMPs), desencadeando uma resposta inflamatórias com produção de diversos mediadores inflamatórios, incluindo citocinas. Desta forma, o objetivo deste estudo foi avaliar o perfil de expressão gênica dos Tolls 1-10, assim como a produção de citocinas pró-inflamatórias TNF-α, IFN-γ, IL-1β e IL-6 no encéfalo e no baço de cães com leishmaniose visceral. No baço houve aumento de expressão gênica de TLR-5 e TLR-9, enquanto no encéfalo houve aumento de TLR-4 em uma pequena população de cães infectados. Em relação às citocinas, todas as citocinas foram detectadas nos dois tecidos avaliados, com excessão de IL-6. Nos cães infectados, TNF-α e IL-1β estavam presentes em maiores concentrações no encéfalo e no baço, respectivamente. Este estudo fornece suporte para explicar o envolvimento de TLRs ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract:Visceral leishmaniasis (VL) is a parasitic disease that presents world distribution, affecting humans and animals. Dogs are considered the main hosts of the disease. Infected dogs with the Leishmania parasite can be asymptomatic or present generalized disorders, including neurological alterations. There are some reports of brain commitment during infection. Nevertheless, neuropathogenesis of VL is not completely elucidated. There are evidences of brain barriers breakdown and of the presence of Leishmania DNA in the brain. Toll-like receptors (TLRs) are innate immune sensors capable of detecting pathogen-associated molecular patterns (PAMPs), trigger an inflammatory response with production of several inflammatory mediators, including cytokines. Therefore, the aim of this study was to evaluate gene expression profile of TLRs1-10, along with the production of proinflammatory cytokines in both brain and spleen in dogs with VL. In spleen there was an upregulation of TLR-5 and TLR-9 while in the brain there was up-regulation of TLR- 4 in a few number of infected animals. Regarding cytokines, all cytokines were detected in both tissues, except IL-6. In the infected dogs, TNF-α and IL-1β were present at higher concentrations in the brain and spleen, respectively. This study provides support to explain the involvement of TLRs in VL and our data confirm the brain as an affected organ in this disease
Doutor

APA, Harvard, Vancouver, ISO, and other styles

38

Vallée, Frédéric. "Synthèse et caractérisation d'un hydrogel d'alginamide pour la régénération de voies nerveuses lésées au sein du Système Nerveux Central chez le rat." Thesis, Vandoeuvre-les-Nancy, INPL, 2007. http://www.theses.fr/2007INPL110N/document.

Full text

Abstract:

Ce travail avait pour objectif la synthèse d’hydrogels d’alginates stables dans le temps et leur évaluation comme support de régénération des voies nerveuses lésées du Système Nerveux Central. Différents dérivés amphiphiles de l’alginate de sodium ont été préparés en fixant chimiquement des chaînes alkyles en C12 à différents taux sur le squelette polymère par l’intermédiaire, soit de liaisons ester (alginates esters), soit de liaisons amide (alginamides) moins sensibles à l’hydrolyse. Le comportement en solution des alginamides a été étudié en termes de stabilité dans le temps, de solubilité, de comportement rhéologique, et de taux de gonflement, puis comparé à celui des alginates esters. Les alginamides ont montré des propriétés en solution différentes de celles des alginates esters, en particulier des contraintes critiques faibles, qui sont les conséquences de la formation d’agrégats liée à l’existence d’une réaction secondaire de réticulation chimique lors de la synthèse. Néanmoins, à des concentrations et taux de greffage appropriés, il est possible d’obtenir un réseau polymère tridimensionnel stabilisé par des associations hydrophobes et pouvant servir de pont de régénération pour l’application visée. L’étude in vivo conclut à l’absence de signe de régénération des voies nerveuses chez les animaux lésées sur une durée d’un an. Toutefois, cette étude a permis de valider la stratégie d’implantation d’un gel physique rhéofluidifiant et thixotrope, de définir des méthodes d’analyse des tissus post mortem en présence d’hydrogel, d’examiner la possibilité d’encapsuler un traitement pharmacologique et de définir un cahier des charges élargi de ce biomatériau (pH, stabilité, gonflement …)
The aim of this work was to synthesise alginate hydrogels, stable in time, and to evaluate their potential use as scaffolds for the damaged nerve regeneration in central nervous system. Various amphiphilic derivatives of sodium alginate were prepared by covalent attachment of alkyl chains (12 carbons) onto the polysaccharide at different substitution ratio, either via ester (alginate ester) or amide (alginamide) linkages, these last ones being more stable toward hydrolysis. The properties in solution of the alginamide derivatives were studied in terms of solubility, stability as function of time, rheological behaviour and swelling ratio. Results were compared to those obtained with the alginate ester family and highlighted a different behaviour for the alginamide series in semi-dilute regime. In particular, alginamide hydrogels exhibited a low critical strain which has been attributed to the presence of aggregates in the solution. The formation of these aggregates was due to the occurrence of a secondary cross-linking reaction during the synthesis of polymers. Nevertheless, it was possible, by appropriate tuning of the substitution yield and of the solution concentration, to obtain a three-dimensional network stabilized by intermolecular hydrophobic interactions, which has been evaluated as regenerative support for the considered application. In vivo studies demonstrated the absence of nerve regeneration for the tested injured animals after one year. However, these studies allowed us to evaluate both the strategy for the implantation of a physical gel exhibiting a shear-thinning and thixotrope behavior and the possibility to encapsulate a pharmacological treatment. An enlarged project specification has also been defined for this biomaterial (pH, stability, swelling ratio…)

APA, Harvard, Vancouver, ISO, and other styles

39

Roche, Anie Kavita. "Evaluation of modifications in the central nervous system during inflammation /." Diss., ON-CAMPUS Access For University of Minnesota, Twin Cities Click on "Connect to Digital Dissertations", 1998. http://www.lib.umn.edu/articles/proquest.phtml.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

AragÃo, Gislei Frota. "Efeitos dos triterpenos α- e β-amirina e de seus derivados acetilados no sistema nervoso central." Universidade Federal do CearÃ, 2008. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1202.

Full text

Abstract:

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
A mistura triterpÃnica de α- e β-amirina (AMI) Ã obtida da planta Protium heptaphyllum Aubl March (FamÃlia Burseraceae), comum em vÃrios estados brasileiros e conhecida popularmente como breu branco, tambÃm Ã utilizada na prÃtica da medicina popular para tratar vÃrias enfermidades. O acetato de α- e β- amirina (AcAMI) Ã a forma acetilada desta mistura triterpÃnica. VÃrios estudos experimentais jÃ foram feitos utilizando estes triterpenos, mas estudos da aÃÃo destes no Sistema Nervoso Central (SNC) ainda sÃo escassos. O objetivo deste trabalho foi avaliar o efeito da administraÃÃo destes compostos naturais em camundongos e verificar uma possÃvel atividade sedativa, ansiolÃtica, antidepressiva e anticonvulsivante, procurando ainda esclarecer por que mecanismos estes compostos agem. A metodologia utilizada foi utilizando testes farmacolÃgicos jÃ descritos na literatura e estudos de doseamento de monoaminas e aminoÃcidos atravÃs de HPLC. Os resultados mostraram que tanto a AMI como o AcAMI mostraram-se bastante ativos farmacologicamente. No teste do Campo Aberto ambas misturas (AMI e AcAMI) administradas por via aguda e sub-crÃnica demonstraram efeitos sedativos, nas doses de 10, 25 e 50 mg/kg, apÃs a constataÃÃo da diminuiÃÃo do movimento exploratÃrio dos animais e do nÃmero de grooming e de rearing, utilizando o diazepam como controle positivo. No Teste do Plus Maze tambÃm ambas as misturas demonstraram atividade ansiolÃtica aumentando o nÃmero de entradas e o tempo de permanÃncia nos braÃos abertos. No teste do nado forÃado, AMI nas doses de 2,5 e 5 mg/kg,, i.p., aumentou o tempo de imobilidade dos animais comparado ao controle, e foi potencializado pela imipramina. No teste de induÃÃo de sono por pentobarbital, AMI e AcAMI tiveram o tempo de sono aumentado de forma significante. As misturas triterpÃnicas apresentaram atividade anticonvulsivante quando a induÃÃo da convulsÃo foi feita com pentilenotetrazol (PTZ) efeito este nÃo aparecendo quando a induÃÃo foi com pilocarpina e estricnina. A atividade sedativa e ansiolÃtica da AMI foram revertidas com a presenÃa de flumazenil, efeito similar ao diazepam. O efeito anticonvulsivante da AMI foi aumentado por drogas que inibem a proteÃna quinase C, polimixina B e estaurosporina. O doseamento de monoaminas de cÃrtex de camundongos tratados com AMI (1, 2,5 e 5 mg/kg) mostrou diminuiÃÃo nas concentraÃÃes de noradrenalina e serotonina. No doseamento de aminoÃcidos, houve aumento nas concentraÃÃes de taurina e tirosina e uma diminuiÃÃo de aspartato, glutamato e GABA nos grupos tratados com AMI e AcAMI na dose de 25 mg/kg, por 7 dias. Conclui-se, portanto com este trabalho, que tanto a AMI e o AcAMI possuem atividades sedativas, ansiolÃticas, antidepressivas e anticonvulsivante e provavelmente estas aÃÃes possam estar ligadas a inibiÃÃo de proteÃna quinase C, envolvimento gabaÃrgico e diminuiÃÃo de monoaminas e aminoÃcidos
The mixture of alpha- and beta-amyrin (AMY) triterpenes was isolated from Protium heptaphyllum Aubl March (Burseraceae) which is a medicinal plant common to several Brazilian states and popularly known as âbreu brancoâ. Although the literature presents several studies with these triterpenes, only a few of them emphasizes the CNS, and almost none were performed with triterpene acetylated derivatives. Then, the objectives of the present work were to evaluate, in mice, sedative, anxiolytic, antidepressant and anticonvulsant activities of these drugs, in order to clarify their mechanisms of action. Besides, measurements of monoamines and amino acids by HPLC, in the cortex of mice treated with these drugs, were also performed. The results showed that not only the mixture of alpha- and beta-amyrin (AMY) but also its acetylated derivative (AcAMY) were pharmacologically active and, at some instances, AcAMY was even more efficacious than AMY. In the open field test, AMY and AcAMY, administered acutely or sub-chronically at the doses of 10, 25 and 50 mg/kg, showed a great sedative effect, as indicated by the significant decrease of the exploratory activity (decrease in the number of crossings) as well as the decrease in numbers of grooming and rearing, as compared to diazepam used as a positive control. In the plus maze test, both drugs presented a potent anxiolytic activity indicated by the increase in the number of entrances as well as in the time spent in the open arms. In the forced swimming test, AMY at the doses 2.5 and 5 mg/kg, i.p., increased the immobility time as compared to control and was potentiated by imipramine. In the barbiturateinduced sleeping time, AMY and AcAMY showed a significant increase in parameter analysed, duration of sleep. Furthermore, AMY and its acetylated derivative showed anticonvulsant activities, in the model of PTZ-induced convulsions, but not in two other convulsion models (pilocarpine- and strychnine-induced convulsions). Sedative and anxiolytic activities of AMY were reversed in the presence of flumazenil, a competitive benzodiazepine action inhibitor, an effect similar to that observed with diazepam. In addition, the anticonvulsant effect of AMY was potentiated by polymyxin B and staurosporine, drugs known to inhibit protein kinase C (PKC). Data from cortical monoamine measurements showed significant decreases in noradrenaline and serotonin concentrations, after mice treatments with AMY (1, 2,5 and 5 mg/kg). As far as the amino acid determination is concerned, results showed an increase in taurine and tyrosine levels, and a decrease in glutamate, aspartate and GABA contents, with AMY and AcAMY at the dose of 25mg/kg for seven days. In conclusion, the present study demonstrated anxiolytic, sedative, antidepressant and anticonvulsant actions in AMY and AcAMY, probably involving PKC inhibition and interaction with BDZ receptor. Decreases in monoamines levels, as noradrenaline and serotonin, and amino acid alterations may also play a role

APA, Harvard, Vancouver, ISO, and other styles

41

Galvani, Aline Faria [UNESP]. "Análise da Frequência de Polimorfismos nos genes IL28B e IL28R1 em pacientes acometidos por Meningioma." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/134110.

Full text

Abstract:

Made available in DSpace on 2016-02-05T18:29:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-08-20. Added 1 bitstream(s) on 2016-02-05T18:33:46Z : No. of bitstreams: 1 000855110_20160820.pdf: 664562 bytes, checksum: b100e2fbde17c774255b11fd563661ba (MD5) Bitstreams deleted on 2016-08-22T16:41:54Z: 000855110_20160820.pdf,. Added 1 bitstream(s) on 2016-08-22T16:42:31Z : No. of bitstreams: 1 000855110.pdf: 1362897 bytes, checksum: 814c66d0d4dd13dba974090ba33240c7 (MD5)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Os meningiomas são os tumores mais frequentes do Sistema Nervoso Central e sua classificação é dada quanto ao tipo celular envolvido e grau de malignidade. Os intérferons (IFNs) foram inicialmente associados à resposta antiviral, contudo, estudos posteriores evidenciaram o envolvimento dessas citocinas na regulação do crescimento celular e no efeito imunomodulatório. A Interleucina 28B (IL28B), membro da família dos IFNs do tipo III, parece estar envolvida na resposta imune antiviral e antitumoral. Sendo assim, o objetivo do presente estudo foi avaliar a frequência de variações genéticas em IL28B e IL28R1 em pacientes acometidos por Meningiomas. Sessenta paciente tratados pelo serviço de Neurocirurgia da UNESP de Botucatu/SP foram incluídos neste estudo. A análise do polimorfismo rs12979860 C/T teve significância estatística quando comparou-se a frequência genotípica da população brasileira em relação a presente casuística. Foi descrito a detecção de novas variações genéticas (missense e silent) nos genes IL28B e IL28R1 ao comparar com as respectivas sequencias referencias disponíveis em banco de dados (NCBI). Estes dados sugerem uma importante relação destas variações genéticas em relação a estrutura e função das proteínas envolvidas, entretanto um estudo mais aprofundado das consequências dessas alterações na gênese e/ou progressão dos meningiomas devem ser considerado
Meningiomas are the most common tumors of the central nervous system, despite being benign and grow slowly, can recur in case of incomplete surgical resection. They are classified according to the cells involved and their rate of malignancy. The role of the immune system in preventing the emergence and progression of tumors has been the subject of many studies in the field of tumor immunology. Interferon (IFNs) were originally associated with antiviral response, however, subsequent studies revealed the involvement of these cytokines in the regulation of cell growth and their immunomodulatory effect.Thus, the aim of this study was to analyze the genetic variation frequency of IL28B and IL28R1 in patients with meningioma. Sixty patients treated by UNESP Neurosurgery service of Botucatu/SP were included in this study. Polymorphism rs12979860 C/T analysis showed statistical significance when compared with healthy Brazilian's genotypic frequency. New genetic variation (missense and silent) were detected in IL28B and IL28R1 through reference sequences analysis (NCBI). These data support an important relation of these genetic variations related to protein functions, however other studies of the consequences of these changes in the development and progression of meningiomas should be considered

APA, Harvard, Vancouver, ISO, and other styles

42

Galvani, Aline Faria. "Análise da Frequência de Polimorfismos nos genes IL28B e IL28R1 em pacientes acometidos por Meningioma /." Botucatu, 2015. http://hdl.handle.net/11449/134110.

Full text

Abstract:

Orientador: Maria Inês de Moura Campos Pardini
Coorientador: Adriana Camargo Ferrasi
Banca: Sílvia Helena Barem Rabenhorst
Banca: Marcelo Lima Ribeiro
Resumo: Os meningiomas são os tumores mais frequentes do Sistema Nervoso Central e sua classificação é dada quanto ao tipo celular envolvido e grau de malignidade. Os intérferons (IFNs) foram inicialmente associados à resposta antiviral, contudo, estudos posteriores evidenciaram o envolvimento dessas citocinas na regulação do crescimento celular e no efeito imunomodulatório. A Interleucina 28B (IL28B), membro da família dos IFNs do tipo III, parece estar envolvida na resposta imune antiviral e antitumoral. Sendo assim, o objetivo do presente estudo foi avaliar a frequência de variações genéticas em IL28B e IL28R1 em pacientes acometidos por Meningiomas. Sessenta paciente tratados pelo serviço de Neurocirurgia da UNESP de Botucatu/SP foram incluídos neste estudo. A análise do polimorfismo rs12979860 C/T teve significância estatística quando comparou-se a frequência genotípica da população brasileira em relação a presente casuística. Foi descrito a detecção de novas variações genéticas (missense e silent) nos genes IL28B e IL28R1 ao comparar com as respectivas sequencias referencias disponíveis em banco de dados (NCBI). Estes dados sugerem uma importante relação destas variações genéticas em relação a estrutura e função das proteínas envolvidas, entretanto um estudo mais aprofundado das consequências dessas alterações na gênese e/ou progressão dos meningiomas devem ser considerado
Abstract: Meningiomas are the most common tumors of the central nervous system, despite being benign and grow slowly, can recur in case of incomplete surgical resection. They are classified according to the cells involved and their rate of malignancy. The role of the immune system in preventing the emergence and progression of tumors has been the subject of many studies in the field of tumor immunology. Interferon (IFNs) were originally associated with antiviral response, however, subsequent studies revealed the involvement of these cytokines in the regulation of cell growth and their immunomodulatory effect.Thus, the aim of this study was to analyze the genetic variation frequency of IL28B and IL28R1 in patients with meningioma. Sixty patients treated by UNESP Neurosurgery service of Botucatu/SP were included in this study. Polymorphism rs12979860 C/T analysis showed statistical significance when compared with healthy Brazilian's genotypic frequency. New genetic variation (missense and silent) were detected in IL28B and IL28R1 through reference sequences analysis (NCBI). These data support an important relation of these genetic variations related to protein functions, however other studies of the consequences of these changes in the development and progression of meningiomas should be considered
Mestre

APA, Harvard, Vancouver, ISO, and other styles

43

Luz, Ana Júlia Bretanha. "Quantificação da carga viral do HIV-1 no líquor : comparação entre os ensaios Abbott m2000rt e COBAS TaqMan v2.0." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/159589.

Full text

Abstract:

Introdução A preocupação crescente com as possíveis consequências da replicação viral no sistema nervoso central mostra a necessidade da detecção do HIV no compartimento cerebral. O teste de PCR em tempo real desenvolvido pela Abbott, o Abbott m2000 RealTime HIV-1 (m2000rt), quantifica a carga viral do HIV em amostras de sangue com um procedimento efetivo e de baixo custo no nosso país, por isso é adotado como método padrão pelo Ministério da Saúde, mas não é utilizado em amostras de líquor. O ensaio produzido pela Roche, o COBAS TaqMan HIV-1, version 2 (COBAS v2.0), é o método de PCR em tempo real que tem sido amplamente utilizado para detectar a carga viral do HIV no compartimento cerebral. No entanto, esse método ainda não foi validado para esse propósito e seu custo pode ser uma limitação em diversas regiões com baixos recursos. Objetivos Considerando que não há uma metodologia padronizada para essa situação específica (detecção do HIV no líquor), nós conduzimos esse estudo a fim comparar os desempenhos dos testes m2000rt e COBAS v2.0, na tentativa de propôr um método alternativo e com baixos custos ao mais utilizado nesse contexto (COBAS v2.0). Métodos O estudo foi realizado no período de maio de 2015 a julho de 2016. O cálculo do tamanho da amostra foi baseado em dados de um estudo piloto que revelaram ser necessário um número mínimo de 37 amostras, para detectar uma diferença de 0,20 log10 na carga viral, com um coeficiente de correlação de 0,979 e um poder de 90%. Essa equação permitiria uma perda de 10%. As amostras de líquor foram coletadas consecutivamente a partir de 37 pacientes HIV positivos atendidos no Hospital de Clínicas de Porto Alegre/RS. Os métodos foram processados de acordo com o proposto pelo fabricante para utilização com amostras de plasma. Pequenas modificações foram necessárias no teste em estudo (m2000rt) para neutralizar qualquer diferença metodológica e evitar vieses de mensuração: o congelamento das amostras foi realizado a -20ºC até o momento da análise. O ensaio COBAS v2.0 foi utilizado como referência, uma vez que é o método mais utilizado. Foram realizadas análises quantitativas com resultados que estavam dentro da faixa linear em ambos os métodos (n = 18). Para tornar os métodos comparáveis, adotou-se o limite de detecção do ensaio m2000rt para ambos (40 cp/mL ou 1,60 log10 cp/mL). Os resultados abaixo do limite de detecção foram apresentados como uma variável categórica, uma vez que não são quantificáveis. O coeficiente de correlação de Pearson foi utilizado para comparar os métodos. A normalidade das variáveis foi então resumida calculando o viés estimado pela diferença média "đ " e o desvio padrão das diferenças realizadas pelo teste t para amostras pareadas. Com base na falta de normalidade dos métodos, o grau de concordância dos resultados das cargas virais de HIV foi analisado pelo índice Kappa. Esse estudo foi aprovado pelo comitê de ética do Hospital de Clínicas de Porto Alegre (RS)/ Brasil, registrado na Plataforma Brasil como sendo CAAE: 35072214.7.0000.532. Conclusão Em conclusão, o teste m2000rt que foi modificado para este ensaio mostrou boa concordância e correlação com o teste mais utilizado nesse contexto e pode ser considerado um método alternativo com resultados semelhantes ao COBAS v2.0 e baixos custos na quantificação da carga viral do HIV no líquor. Sugerimos, principalmente em locais onde este método está prontamente disponível com uma relação custo-benefício aceitável, que o exame m2000rt deva ser realizado.
Introduction Growing concern about possible consequences of viral replication in the central nervous system shows the need for HIV detection in the cerebral compartment. The real time PCR test developed by Abbott, Abbott RealTime m2000 HIV-1 (m2000rt) quantifies HIV viral load in blood samples effectively and with low costs Brazil. It is the standard method by the Brazilian Ministry of Health, but it has never been utilized to measure HIV in cerebrospinal fluid samples. The assay produced by Roche, COBAS TaqMan HIV-1, version 2 (COBAS v2.0) is the real-time PCR method that has been widely used to detect HIV viral load in cerebral compartment. However, this method has not yet been validated for this purpose and its cost may be a limitation in several regions in the world with low resources. Objective Taking under consideration that there was no standard methodology for this specific situation (detecting HIV in cerebrospinal fluid), we conducted this study to compare the performances of the m2000rt and COBAS v2.0 assays, to propose an alternative and low-cost method to more used in this context (COBAS v2.0). Methods The study was conducted from May 2015 to July 2016. The sample size calculation was based on data from a pilot trial that revealed that a minimum of 37 samples would be needed to detect a difference of 0.20 log10 in viral load, with a correlation coefficient of 0.979 and a 90% power. This equation would allow a 10% lost. CSF samples were collected consecutively from 37 HIV-positive patients seen at Hospital de Clínicas, Porto Alegre, RS. Methods were processed according to proposed by the manufacturer for utilization with plasma samples. Small modifications were necessary in the study test (m2000rt) to neutralize any methodological differences, thus avoiding measurement bias: the freezing of samples was carried out at -20ºC until the moment of the analysis. The COBAS v2.0 test was used as a reference since it is the most commonly used method. Quantitative analyzes were performed with results that were within the linear range in both methods (n=18). To make the methods comparable, the detection limit of the m2000rt assay for both (40 cp/mL or 1.60 log10 cp/mL) was adopted. The results below the limit of detection were presented as a categorical variable, since they are not quantifiable. The Pearson correlation coefficient was used to compare methods. The normality of the variables was then summarized calculating the estimated bias by the mean difference "đ" and standard deviation of the differences performed by t test for paired samples. Based on the lack of normality of the methods, the degree of agreement of the HIV viral load results was analyzed by the Kappa index. This study was approved by the Hospital de Clínicas of Porto Alegre (southern Brazil) Ethics Review Board, registered in the Brazil Platform as CAAE: 35072214.7.0000.532. Conclusion In conclusion, the m2000rt test that was modified for this trial showed good agreement and correlation with the most used test in this context and can be considered an alternative method with similar results to COBAS v2.0 and low costs in the HIV viral load quantification in cerebrospinal fluid. We suggest, especially in places where this method is readily available with an acceptable cost-benefit ratio, that the m2000rt exam should be performed.

APA, Harvard, Vancouver, ISO, and other styles

44

Poland, Stephen D. "Central nervous system infection with human cytomegalovirus." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq21311.pdf.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Hüppi, Petra Susan. "Serum antibodies to central nervous system antigens /." [S.l : s.n.], 1986. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Bernick, Kristin Briana. "Cell biomechanics of the central nervous system." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/67202.

Full text

Abstract:

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2011.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 133-153).
Traumatic brain injury (TBI) is a significant cause of death and morbidity in both the civilian and military populations. The major causes of TBI, such as motor vehicle accidents, falls, sports concussions, and ballistic and explosive blast threats for military personnel, are well established and extensively characterized; however, there remains much to be learned about the specific mechanisms of damage leading to brain injury, especially at the cellular level. In order to understand how cells of the central nervous system (CNS) respond to mechanical insults and stimuli, a combined modeling/experimental approach was adopted. A computational framework was developed to accurately model how cells deform under various macroscopically imposed loading conditions. In addition, in vitro (cell culture) models were established to investigate damage responses to biologically relevant mechanical insults. In order to develop computational models of cell response to mechanical loading, it is essential to have accurate material properties for all cells of interest. In this work, the mechanical responses of neurons and astrocytes were quantified using atomic force microscopy (AFM) at three different loading rates and under relaxation to enable characterization of both the elastic and viscous components of the cell response. AFM data were used to calibrate an eight-parameter rheological model implemented in the framework of a commercial finite element package (Abaqus). Model parameters fit to the measured responses of neurons and astrocytes provide a quantitative measure of homogenized nonlinear viscoelastic properties for each cell type. In order to ensure that the measured responses could be considered representative of cell populations in their physiological environment, cells were also grown and tested on substrates of various stiffness, with the softest substrate mimicking the stiffness of brain tissue. Results of this study showed both the morphology and measured force response of astrocytes to be significantly affected by the stiffness of their substrate, with cells becoming increasingly rounded on soft substrates. Results of simulations suggested that changes in cell morphology were able to account for the observed changes in AFM force response, without significant changes to the cell material properties. In contrast, no significant changes in cell morphology were observed for neurons. These results highlight the importance of growing cells in a biologically relevant environment when studying mechanically mediated responses, such as TBI. To address this requirement, we developed two model systems with CNS cells grown in soft, 3D gels to investigate damage arising from dynamic compressive loading and from a shock pressure wave. These damage protocols, coupled with the single cell computational models, provide a new tool set for characterizing damage mechanisms in CNS cells and for studying TBI in highly controllable in vitro conditions.
by Kristin Briana Bernick.
Ph.D.

APA, Harvard, Vancouver, ISO, and other styles

47

Coutinho, Maria Ester Freitas Barbosa Pereira. "Central nervous system autoimmunity in neuropsychiatric disorders." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:389fb830-4b4e-4201-9965-19acb2c63ff3.

Full text

Abstract:

The recent history of autoimmune neurology is marked by the discovery of many central nervous system (CNS) antibody-mediated diseases. These disorders are caused by antibodies that target important proteins expressed in the neuronal surface, which are believed to be directly pathogenic. These antibodies are immunoglobulin G (IgG) isotype and, as such, have the potential to cross the placenta during gestation. Foetal exposure to CNS-targeting antibodies could alter developing neuronal circuits, leading to disease. However, the consequences of exposure to these antibodies during neurodevelopment has hardly been considered. To study the relationship between maternal antibodies towards neuronal surface proteins and neurodevelopmental disorders in the foetus a dual approach was undertaken. First, pregnancy serum samples from mothers of children later diagnosed with a neurodevelopmental disorder and from mothers of children with typical development were screened for the presence of neuronal surface antibodies. Next, the effects of pathogenic neuronal surface antibodies in the offspring were assessed in a maternal-to-foetal transfer mouse model. Antibodies to neuronal surface proteins in the gestational serum, particularly CASPR2 antibodies, were found to associate with an increased risk of mental retardation and disorders of psychological development in the progeny. The animal model showed that mice exposed in utero to CASPR2 antibodies have long term behavioural sequelae and histological findings suggestive of abnormalities in brain development. These findings support a model in which maternal antibodies towards foetal neuronal proteins cause long-term behavioural deficits and permanent abnormalities at the cellular and synaptic level in a subset of children with neurodevelopmental disorders.

APA, Harvard, Vancouver, ISO, and other styles

48

Chan, Pok-man. "Cloning of hamster GAP-43 to study the expression and regulation of GAP-43 mRNA in the retina during degeneration and regeneration /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B2063299X.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Hantraye, Philippe. "Physiologie et physiopathologie des recepteurs des benzodiazepines de type central : etudes chez le singe et l'homme par tomographie par emission de positons." Paris 6, 1987. http://www.theses.fr/1987PA066425.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

Eckert, Bodil. "Hypoglycaemia studies on central and peripheral nerve function /." Lund : Dept. of Internal Medicine, University of Lund, 1998. http://catalog.hathitrust.org/api/volumes/oclc/57426099.html.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Dissertations / Theses on the topic 'Central nervous systems'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles