Dissertations / Theses on the topic 'Brain stem'
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1
Carlén, Marie. "Adult neurogenesis : from stem cell to functional neuron /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-367-1/.
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Bruggeman, Kiara. "How to build a brain." Thesis, https://youtu.be/yTkSAceGenw, 2014. http://hdl.handle.net/1885/14128.
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Your cells are magnificent little things, every single one is full of complex microsystems all working together to keep you going. They’re more intricate and advanced than any machines we can make, but sometimes… they need a little help to get going. Stem cells are like tiny teenagers, they’re full of potential but they need a kick in the pants to get going, and that’s where I come in. After a stroke, patients are left with chunks of damaged brain tissue. Now, instead of trying to rebuild the incredibly complex human brain from scratch, I’d much give cells the support and encouragement they need to rebuild it themselves. My research goal is to rebuild damaged brain tissue, but in truth, stem cells will be doing all the actual building, I’m just making materials that tell them how to build a brain.
3
Paues, Jakob. "Brain Stem Involvement in Immune and Aversive Challenge." Doctoral thesis, Linköping : Linköping University, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-7579.
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Marciszewski, Kasia. "Does Migraine Stem From the Brainstem?" Thesis, The University of Sydney, 2019. https://hdl.handle.net/2123/21241.
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The exact neural mechanisms underlying migraine have been strongly debated for decades. It is well accepted the trigeminovascular system plays a role in migraine, however the precise neurobiological mechanism by which migraine attacks are initiated is presently unknown. Existing literature has demonstrated that even between attacks, the migraine brain differs from that of controls and has led to the current theory of migraine as a “cycling” brain disorder. This suggests that the changes observed in migraine are not fixed, but rather dynamic in nature, and that function, sensitivity and even anatomy of the brainstem may fluctuate throughout the migraine cycle. However, while the brainstem has been heavily implicated in migraine pathogenesis, it has been poorly studied by neural imaging investigations. Likewise, the spontaneous and episodic nature of migraines has made it difficult to study the migraine cycle in its entirety. As such, this thesis aimed to explore brainstem anatomy, functional connectivity, and sensitivity to noxious stimuli, in migraineurs across the entire migraine cycle. The investigations performed in this thesis, consistently revealed key brainstem pain-processing regions, such as the spinal trigeminal nucleus and periaqueductal grey matter, as having altered anatomy, functional connectivity, and sensitivity across the migraine cycle. Most intriguingly, these changes were most dramatically altered in the 24 hours immediately prior to migraine onset. This suggests the observed changes in these brainstem regions may underlie the processes causing migraine initiation. Furthermore, these changes were dynamic in nature, supporting the notion of a “cycling” migraine brain. This opens new avenues for migraine research which will hopefully lead to better prophylactic treatments, capable of controlling these fluctuations that underlie the disorder.
5
Wennersten, Andrʹe. "Human neural stem cell transplantation in experimental brain trauma /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-211-X/.
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Ringstedt, Thomas. "Neurotrophins during development : overexpression in neural stem cells /." Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980605ring.
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Parker, Graham Charles. "Cholinergic stimulation of the substantia negra." Thesis, University of St Andrews, 1993. http://hdl.handle.net/10023/14733.
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Convergent lines of research suggest there exists an excitatory cholinergic input to the substantia nigra from the pedunculopontine tegmental nucleus and possibly the laterodorsal tegmental nucleus. Previous work has suggested that microinjection of cholinergic agonists into substantia nigra elicits behaviours performed with a high frequency but with a low current rate (Winn 1991). Experiments carried out during my PhD have demonstrated that: Microinjection of cholinergic agonists to anterior substantia nigra (SN) elicited increased consumption of palatable food such as spaghetti but not rat maintenance diet in pre-satiated rats. Stimulation of behaviour was achieved using direct agonists for either muscarinic or nicotinic cholinergic receptors (carbachol and nicotine respectively). Stimulation of behaviour was also achieved using the indirect cholinergic agonist neostigmine which blocks the de-activation of endogenous acetylcholine by AChE. Increased feeding elicited by cholinergic stimulation of the anterior SN was abolished by a selective lesion of ascending dopamine (DA) neurones which significantly depleted caudate DA levels but left accumbens DA levels unaltered. A behaviourally potent dose of carbachol caused a significant increase in the response to different doses of nicotine suggesting an additive effect of muscarinic and nicotinic stimulation at the doses used. Administration of cholinergic agonists to the VTA or SN caused indistinguishable effects on responding for conditioned reinforcement. Cholinergic stimulation caused increased responding for a conditioned reinforcer and also reinstated responding at the primary reward source. The functional significance of the cholinergic innervation of the DA- containing neurones of the substantia nigra is discussed with reference to its relationship to the neighbouring ventral tegmental area, and their innervation of the caudate-putamen and the nucleus accumbens. Cholinergic neurones in the PPTg and LDTN appear to exert a tonic control over the activity of midbrain DA-containing neurones. It is suggested that cholinergic control of midbrain DA-containing neurones facilitates the processing of information in the striatum and hence influence the selection of an appropriate behavioural response to a given situation.
8
Keating, Glenda Louise. "Examination of the role of the pedunculopontine tegmental nucleus in the control of behavioural processes." Thesis, University of St Andrews, 1998. http://hdl.handle.net/10023/14737.
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The role of the pedunculopontine tegmental nucleus (PPTg) in the control of behavioural processes was investigated in this thesis. This was achieved through examination of: (1) Conditioned place preference formation: PPTg lesioned rats were not impaired in forming an appropriate place preference, regardless of their deprivation state. (2) Reward-related responding: both food deprived and non-deprived lesioned rats displayed disinhibited intake across a gradient of sucrose rewards, the degree of disinhibition increasing as the reward became stronger. This disinhibited responding was disassociated from simple approach behaviour as shown by similar runway completion times across control and lesioned rats. (3) Radial arm maze performance: PPTg lesioned rats were impaired in their ability to retrospectively plan and forage in a random foraging task. This impairment was seen in both acquisition and retention tasks. PPTg lesioned rats were also impaired in the acquisition of a spatial working memory task in which they had to prospectively plan and execute responses. (4) These behavioural tasks are related to striatal output. To complement them anatomical experiments examining altered striatal outflow on neurotransmitter expression in the PPTg were conducted. Neither dopamine receptor blockade nor 6- hydroxydopamine (6-OHDA) lesions of striatal dopamine produced changes in nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase expression in the PPTg. This work did, however, lay the foundation for future experimentation to address this question. The combination of these findings extends current literature to outline a role for the PPTg in the control of complex behaviours that have been previously associated with sites higher up the neuraxis. This thesis demonstrates that removal of the PPTg results in behaviours that are inappropriate and disinhibited. In conclusion the PPTg is important for both accurate response selection and execution of goal directed behaviours, elements crucial for effective behavioural responding.
9
Gupta, Kunal. "Using human embryonic stem cells to model acute brain injury." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610468.
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Capela, Maria Alexandra Nunes. "Neural stem cells in the embryonic and adult mouse brain." Doctoral thesis, Porto : Edição do Autor, 2002. http://hdl.handle.net/10216/64573.
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Capela, Maria Alexandra Nunes. "Neural stem cells in the embryonic and adult mouse brain." Tese, Porto : Edição do Autor, 2002. http://catalogo.up.pt/F?func=find-b&local_base=UPB01&find_code=SYS&request=000090403.
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Cusulin, Carlo. "Neural stem cells and their interaction with the brain environment." Doctoral thesis, Università degli studi di Trieste, 2010. http://hdl.handle.net/10077/3661.
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2008/2009The NS culture system is an innovative yet not fully characterized method of culturing neural stem cells (NSCs). Previous reports have described the possibility of isolation of a virtually pure NSC culture from embryonic, fetal or adult NSCs (Conti et al., 2005; Pollard et al., 2006; Sun et al., 2008). These cells, grown in adhesion, are called NS cells and show radial glial characteristics. The present thesis aims to characterize the in vitro and in vivo behaviour of human and mouse NS cells. In the first study, we describe the isolation of a new strain of human striatal NS cells. They show unique features in vitro, and can be efficiently differentiated into neurons. After transplantation in newborn rats, they survive, migrate and differentiate in the host brain. In the second part of the thesis, we show that mouse ES-derived NS cells fuse with cortical pyramidal neurons after transplantation in mice or rats. This process is mediated by microglia, which first fuse with the NS cells and then with the neurons. This NS-microglia-neuron fusion has not been previously described, although it occurs both in vivo and in vitro. In summary, we report here previously undescribed features of the NS cells; our results are relevant to better understanding of NSCs in general and their behaviour after transplantation in the brain.
XXII Ciclo
1981
13
Stewart, William. "The organisation of the monoaminergic and cholinergic systems in the spinal cord." Thesis, University of Glasgow, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366198.
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Ronca, April E. "The effects of decerebration prior to maturation: species-typical behavior, sensory processes, and learning /." The Ohio State University, 1987. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487329662146174.
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Tropepe, Vincent. "Origin and diversification of neural stem cells during mammalian brain development." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0017/NQ53655.pdf.
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Hertwig, Falk [Verfasser]. "Development of brain tumors from neural stem, progenitor cells / Falk Hertwig." Berlin : Freie Universität Berlin, 2012. http://d-nb.info/1027308503/34.
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Hayashi, Junya. "Primate embryonic stem cell-derived neuronal progenitors transplanted into ischemic brain." Kyoto University, 2006. http://hdl.handle.net/2433/135623.
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Mannino, Mariella. "Improving treatment of glioblastoma : new insights in targeting cancer stem cells effectively." Thesis, University of Sussex, 2015. http://sro.sussex.ac.uk/id/eprint/58695/.
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Glioblastoma is the most common primary malignant brain tumour in the adult population. Despite multimodality treatment with surgery, radiotherapy and chemotherapy, outcomes are very poor, with less than 15% of patients alive after two years. Increasing evidence suggests that glioblastoma stem cells (GSCs) are likely to play an important role in the biology of this disease and are involved in treatment resistance and tumour recurrence following standard therapy. My thesis aims to address two main aspects of this research area: 1) optimization of methods to evaluate treatment responses of GSCs and their differentiated counterparts (non-GSCs), with a particular focus on a tissue culture model that resembles more closely the tumoral niche; 2) characterization of cell division and centrosome cycle of GSCs, investigating possible differences between these cells and non-GSCs, that would allow the identification of targets for new therapeutic strategies against glioblastomas. In the first part of my project, I optimized a clonogenic survival assay, to compare sensitivity of GSCs and non-GSCs to various treatments, and I developed the use of a 3-dimentional tissue culture system, that allows analysis of features and radiation responses of these two subpopulations in the presence of specific microenvironmental factors from the tumoral niche. In the second part, I show that GSCs display mitotic spindle abnormalities more frequently than non-GSCs and that they have distinctive features with regards to the centrosome cycle. I also demonstrate that GSCs are more sensitive than non-GSCs to subtle changes in Aurora kinase A activity, which result in a rapid increase in polyploidy and subsequently in senescence, with a consistent reduction in clonogenic survival. Based on these findings, I propose that kinases involved in the centrosome cycle need to be explored as a novel strategy to target GSCs effectively and improve outcomes of glioblastoma patients.
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Punjaruk, Wiyada. "The contribution of drug resistant cancer stem cells to paediatric brain tumours." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/13403/.
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Introduction: Recent studies have revealed that cancer stem cells (CSCs) exist in malignant disease. Additionally, it is proposed that these cells may survive following chemotherapy, and hence contribute to tumour relapse. A significant mechanism of drug resistance in CSCs is believed to be the expression of ATP-binding cassette (ABC) transporters that efflux cytotoxic agents out of cells. The objective of this study was to study the existence of CSCs in a panel of primary paediatric brain tumours (PBTs) and to determine if these were drug resistant via functional ABC transporters. Materials and Methods: The main cell lines characterised were: EPN-2 (primary ependymoma); MED-2 (recurrent medulloblastoma); SPNET-1 [primary CNS primitive neuroectodermal tumour (CNS PNET)]; and a commercial CNS PNET (PFSK-1). Basic characterisation of our cell lines were assessed by Telomeric Repeat Amplification Protocol (TRAP) assay, Terminal Restriction Fragments (TRF) assay, metaphase spread analysis and doubling time. To determine the proportion of cancer stem-like cells in the parental cell lines, CD133 and SOX2 co-staining immunofluorescence was performed and validated by Western blotting analysis. The expression of ABC transporters (ABCB1, ABCC1 and ABCG2) was also investigated by co-staining for CD133 and ABC transporters using immunofluorescence and Western blotting analysis. Flow cytometry was performed to examine ABCB1 function. Four clinically relevant drugs (etoposide, cisplatin, irinotecan and methotrexate) were used to assess the degree of drug resistance of these lines. Clonnogenic assay and neurosphere formation assay were then performed to investigate colony survival and the ability of cells to form neurospheres, respectively, after drug treatment. Finally, the potential to increase chemosensitivity by drug treatment in the presence of the ABCB1 inhibitor, Verapamil, was assessed. Results: Basic characterisation results demonstrated that a high level of telomerase activity and maintenance of telomere length was found in all cell lines (grown both as monolayers and neurospheres). Metaphase spread analysis showed a wide range of aberrant chromosome numbers in PFSK-1 cells whereas our cell lines demonstrated a more stable chromosome number. Neurospheres grew slower than monolayers and monolayers had constant growth rate with increasing passage number. It was found that for each cell line, a small subpopulation (8-12%) of cultured monolayer cells are positive for both CD133 and SOX-2 immunofluorescent staining whilst cultured neurospheres contained 35-45% of co-stained cells. No co-stained cells were identified in the commercial PFSK-1 line and these findings were consistent with the results from Western blotting analysis. Approximately 10% of the parental cell lines comprised cells co-expressing CD133 and ABCB1 or ABCC1 at a low level whilst none of our cell lines were positive for ABCG2. Additionally, the parental cell lines contained a small proportion of cells expressing functional endogenous ABCB1 (34±5.2% in EPN-2, 26.5±3.9% in MED-2 and 13.9±3.2% in SPNET-1). During multiple rounds of drug treatment, ABCB1 was consistently expressed at a high level throughout and the proportion of functional ABCB1 expressing cells increased in all cell lines almost 2 fold compared to the parental cell lines and the selected control sublines. Whilst ABCC1 expression was gradually upregulated after multiple rounds of treatment but ABCG2 expression remained negative. Drug combined with Verapamil treatment significantly decrease survival rate approximately 5 fold compared to drug treatment alone although the majority of surviving cells were still CD133 and ABCB1 positive. Conclusion: Newly established paediatric cell lines (EPN-2, MED-2 and SPNET-1) represented significant histological and biological features of the original tumours from which they were derived and were stable in standard culture condition for a prolonged period of time. The parental cell lines contained a small proportion of cells expressing endogenous functional ABCB1 at a low level indicating intrinsic drug resistance. After multiple rounds of drug treatment, ABCB1 was the major mechanism of drug resistance in our cell lines. ABCC1 were upregulated later in our cell lines after multiple rounds of drug treatment whereas none of our cell lines expressed ABCG2 during drug treatment.
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Perruisseau-Carrier, Claire. "Neuronal commitment of Umbilical Cord Mesenchymal Stem Cells for brain regenerative medicine." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10192.
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De nos jours, aucune prévention ou aucun remède efficace n'existe pour guérir les maladies du cerveau humain. Les cellules souches représentent un grand espoir pour la réparation et la régénération des tissus neuraux endommagés. L'objectif de cette thèse est d'évaluer la capacité des cellules souches du cordon ombilical humain (hUC MSCs) à se différencier en neurones, pour une thérapie cellulaire appliquée au cerveau. Nous avons isolé, multiplié et caractérisé les hUC MSCs naïves à l'échelle des gènes et des protéines. Ensuite, les e_ets sur l'expansion des hUC MSCs et leur différenciation neuronale de différents paramètres ont été évalués par qPCR et marquages immunologiques principalement: milieux et matrices de culture, oxygénation, culture en 3D, ainsi que divers facteurs et molécules tels que les microARNs. Les résultats montrent que les hUC MSCs prolifèrent mieux sans sérum et en conditions de normoxie du cerveau (1-5 % O2). Les hUC MSCs naïves semblent préparées à devenir des neurones à l'échelle des gènes et des protéines, mais pas suffisamment pour supporter leur complète différenciation. L'introduction de microARNs requiert des améliorations pour réguler efficacement les voies de signalisation des hUC MSCs. Au cours de cette étude, nous avons identifé les paramètres favorisant l'expansion des hUC MSCs dans des conditions compatibles avec la clinique. Cependant, une question reste ouverte: les hUC MSCs sont-elles capables de vraie transdifferentiation en neurones fonctionnels malgré les controverses? Des recherches supplémentaires sont nécessaires, mais cette étude constitue une première étape vers l'utilisation des hUC MSCs en médecine régénératrice du cerveauNowadays, no effective prevention or cure of human brain diseases is available. Stem cells hold great promise for the repair and regeneration of damaged neural tissues. This thesis aims to evaluate the potency of human umbilical cord mesenchymal stem cells (hUC MSCs) to be committed to the neuronal lineage, for brain cell-based therapy. To achieve this goal, naive hUC MSCs were isolated, expanded, and characterized at the gene and protein level, while particularly focusing on the neuronal lineage and clinical-grade culture conditions. Then, several parameters were investigated for hUC MSCs proliferation and neuronal commitment, including media, coatings, 3D culture, hypoxia, chemicals and molecules. Growth curves drawings, qPCRs, and immunostainings were used among other methods for identifying the best conditions for hUC MSCs expansion, differentiation, culture in 3D, and microRNAs delivery. The results indicate that hUC MSCs better proliferate in serum-free media and brain's normoxia condition (1-5 % O2). Naive hUC MSCs appear primed for neuronal fate at gene and protein level, but not su_ciently to support their neuronal di_erentiation. microRNAs delivery requires further improvement to efficiently promote neuronal signaling pathways in hUC MSCs. Along this study we identified the best parameters for hUC MSCs expansion in clinical-grade conditions. However, a question still remains: are hUC MSCs capable of full transdifferentiation towards functional neurons despite all controversies? Additional work is needed, but this study is a first step towards answering this question, bringing more clues to make transplantation of hUC MSCs for brain regenerative medicine closer
21
Crutchfield, Susan R. "Contiguous visual and brain stem auditory evoked potential recordings of premature infants." Thesis, Aston University, 1985. http://publications.aston.ac.uk/14584/.
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Irons, Hillary Rose. "Bone marrow-derive mesenchymal stem cell as an alternate donor cell source for transplantation in tissue-engineered constructs after traumatic brain injury." Available online, Georgia Institute of Technology, 2007, 2007. http://etd.gatech.edu/theses/available/etd-07092007-095239/.
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Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2008.LaPlaca, Michelle, Committee Chair ; McDevitt, Todd, Committee Member ; Lee, Robert, Committee Member ; Archer, David, Committee Member ; Lambert, Nevin, Committee Member.
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Feldman, Danielle A. (Danielle Anagela). "Human induced pluripotent stem cell models of Rett Syndrome reveal deficits in early cortical development." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/107869.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2016.Cataloged from PDF version of thesis.
Includes bibliographical references.
Rett Syndrome (RTT) is a pervasive, X-linked neurodevelopmental disorder that predominantly affects girls. The clinical patient features of RTT are most commonly reported to emerge between the ages of 6-18 months and as such, RTT has largely been considered to be a postnatal disorder. The vast majority of cases are caused by sporadic mutations in the gene encoding methyl CpG-binding protein 2 (MeCP2), which is expressed in the brain during prenatal neurogenesis and continuously throughout adulthood. MeCP2 is a pleiotropic gene that functions as a complex, high-level transcriptional modulator. It both regulates and is regulated by coding genes and non-coding RNAs including microRNAs (miRNAs). The effects of MeCP2 are mediated by diverse signaling, transcriptional, and epigenetic mechanisms. Whereas the postnatal effects of MeCP2 have been widely studied, pre-symptomatic stages of RTT have yet to be thoroughly investigated. Recent evidence from our lab among others suggests a role for MeCP2 during prenatal neurogenesis that may contribute to the neuropathology observed later in life. We sought to characterize the course of neurogenesis in MeCP2-deficient human neurons with the use of induced pluripotent stem cells (iPSCs) derived from RTT patient skin samples. We generated a variety of monolayer and 3D neuronal models and found that RTT phenotypes are present at the earliest stages of brain development including neuroepithelial expansion, neural progenitor migration and differentiation, and later stages of membrane and synaptic physiological development. We established a link between MeCP2 and key microRNAs that are misregulated in RTT and lie upstream of signalling pathways that contribute to aberrant neuronal maturation in the absence of MeCP2. We have uncovered novel roles of MeCP2 in human neurogenesis. Whereas the processes that comprise early neural development were previously considered irrelevant to RTT pathology, the deficits we observed in neuronal differentiation, migration, and maturation are a crucial component to the larger picture of RTT pathogenesis and provide additional insight into the emergence of RTT patient symptoms.
by Danielle A. Feldman.
Ph. D.
24
Momma, Stefan. "Neural stem cells and their contribution to neurogenesis in the adult mammalian brain /." Stockholm : Karolinska institutet, 2002. http://diss.kib.ki.se/2002/91-7349-324-4/.
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Rippaus, Nora. "Development of a haematopoietic stem cell-based cell therapy to treat brain metastases." Thesis, University of Leeds, 2015. http://etheses.whiterose.ac.uk/11892/.
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Over the last decades, the occurrence of patients with brain metastases, originating mostly from melanoma, lung and breast cancer, has increased. Despite some progress, there are still no effective therapies that target brain metastases. Due to the blood-brain barrier, which restricts the access of conventional therapies to the central nervous system, therapeutic strategies need to include novel means of drug delivery. Furthermore, these therapies have to target multiple lesions simultaneously, as brain lesions often present multifocally. This study aimed to develop a Haematopoietic stem cell (HSC)-based therapy that has the potential to overcome these limitations. In doing so, the suitability of HSCs and their myeloid progeny as cellular delivery vehicles for the delivery of genetically encoded therapeutic molecules into brain metastases was investigated. A strong infiltration of murine and human brain metastases tissue by the myeloid progeny of HSCs, which mostly consisted of macrophages, was demonstrated. Moreover, following ex vivo modification, the progeny of HSCs were able to deliver an expressed transgene to the proximity of brain metastases in preclinical models. To reduce the toxic effect of the delivered therapeutic molecules, an enzyme prodrug approach was developed and tested in the context of HSC therapy for targeting of brain metastases. In addition to homing to brain metastases, the progeny of HSCs also infiltrates organs. In the context of the cell therapy this could lead to the accumulation of therapeutic molecules at those sites, resulting in possible side effects of the therapy. To address this issue, three promoters with high specificity and activity in murine and human brain metastases-infiltrating myeloid cells were identified, which could be used to restrict the delivery of genetically encoded therapeutic agents to brain metastases.
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Speccher, Alessandra. "Tissue engineering approaches for brain injury applications." Doctoral thesis, Università degli studi di Trento, 2020. http://hdl.handle.net/11572/262798.
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Due to the limited regenerative capacity of the central nervous system (CNS) upon injury, regenerative medicine and tissue engineering strategies show great promise for treatment. These aim to restore tissue functions by combining principles of cell biology and engineering, using biomaterial scaffolds which can help in recapitulating the 3D environment of the brain and improving cell survival after grafting.
Stroke and TBI are severe forms of disruptions of brain architecture, and two of the leading causes of mortality and morbidity worldwide, as no effective treatments are available. Several studies report how neural stem cells (NSCs) are able to improve functional recovery upon transplantation. However, the efficacy of these treatments is limited because of the mortality these cells are subject to after transplantation. In this context, the transplantation of mesenchymal cells (MSCs) has shown beneficial effects by secreting molecules and factors that help in the healing process.
In this study, we tested alginate-based hydrogels as candidates to support human NSCs and MSCs transplantation into the brain, in the view of exploiting the beneficial effects of both and analyzing whether their combined use could have a synergistic effect.
In the first part, we studied the suitability of alginate-based scaffolds for the three-dimensional encapsulation and culture of hNSCs and hMSCs. We analyzed their ability to support cell survival, and we evaluated whether changes in their concentration or modifications with ECM molecules could influence cell viability. We showed that the best survival conditions are found when using an RGDs-functionalized alginate scaffold at a low concentration (0.5% w/v). We then worked on the identification of the best conditions for MSCs culture and the definition of coculture conditions. Since serum is necessary for MSCs, but it is reported to induce glial differentiation of NSCs, we explored two different experimental setups. On one hand, we investigated the feasibility to exploit biomaterials to create "compartmentalized" cocultures that would at least partially retain serum. In parallel, we positively observed that MSCs can survive, proliferate and maintain their stemness even in absence of serum, supporting the hypothesis that the use of “compartmentalized” coculture systems would likely be exploitable for MSCs culture.
Finally, we tested the reported beneficial effects of MSCs in our 3D culture system, in which NSCs do not show a great viability. Encapsulated NSCs were cultured on an MSCs monolayer, and we analyzed cell survival, proliferation, differentiation and stemness retention. Gene expression analyses highlighted that NSCs maintain stemness characteristics, but we were not able to observe any improvement in NSCs survival in coculture, with respect to standard culture.
In the last part of the project we decided to test our system for tissue engineering approaches, exploiting axotomized brain organotypic slices (OSCs). We evaluated the presence of cells 7 days after transplantation, their integration in the OSCs and glial response. Preliminary results suggest that the biomaterial does not cause activation of glial cells, although stem cells do not seem to migrate out of scaffold and integrate into the brain slice.
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Speccher, Alessandra. "Tissue engineering approaches for brain injury applications." Doctoral thesis, Università degli studi di Trento, 2020. http://hdl.handle.net/11572/262798.
Full textAbstract:
Due to the limited regenerative capacity of the central nervous system (CNS) upon injury, regenerative medicine and tissue engineering strategies show great promise for treatment. These aim to restore tissue functions by combining principles of cell biology and engineering, using biomaterial scaffolds which can help in recapitulating the 3D environment of the brain and improving cell survival after grafting.
Stroke and TBI are severe forms of disruptions of brain architecture, and two of the leading causes of mortality and morbidity worldwide, as no effective treatments are available. Several studies report how neural stem cells (NSCs) are able to improve functional recovery upon transplantation. However, the efficacy of these treatments is limited because of the mortality these cells are subject to after transplantation. In this context, the transplantation of mesenchymal cells (MSCs) has shown beneficial effects by secreting molecules and factors that help in the healing process.
In this study, we tested alginate-based hydrogels as candidates to support human NSCs and MSCs transplantation into the brain, in the view of exploiting the beneficial effects of both and analyzing whether their combined use could have a synergistic effect.
In the first part, we studied the suitability of alginate-based scaffolds for the three-dimensional encapsulation and culture of hNSCs and hMSCs. We analyzed their ability to support cell survival, and we evaluated whether changes in their concentration or modifications with ECM molecules could influence cell viability. We showed that the best survival conditions are found when using an RGDs-functionalized alginate scaffold at a low concentration (0.5% w/v). We then worked on the identification of the best conditions for MSCs culture and the definition of coculture conditions. Since serum is necessary for MSCs, but it is reported to induce glial differentiation of NSCs, we explored two different experimental setups. On one hand, we investigated the feasibility to exploit biomaterials to create "compartmentalized" cocultures that would at least partially retain serum. In parallel, we positively observed that MSCs can survive, proliferate and maintain their stemness even in absence of serum, supporting the hypothesis that the use of “compartmentalized” coculture systems would likely be exploitable for MSCs culture.
Finally, we tested the reported beneficial effects of MSCs in our 3D culture system, in which NSCs do not show a great viability. Encapsulated NSCs were cultured on an MSCs monolayer, and we analyzed cell survival, proliferation, differentiation and stemness retention. Gene expression analyses highlighted that NSCs maintain stemness characteristics, but we were not able to observe any improvement in NSCs survival in coculture, with respect to standard culture.
In the last part of the project we decided to test our system for tissue engineering approaches, exploiting axotomized brain organotypic slices (OSCs). We evaluated the presence of cells 7 days after transplantation, their integration in the OSCs and glial response. Preliminary results suggest that the biomaterial does not cause activation of glial cells, although stem cells do not seem to migrate out of scaffold and integrate into the brain slice.
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Cullen, Daniel Kacy. "Traumatically-induced degeneration and reactive astrogliosis in three-dimensional neural co-cultures." Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-11282005-210117/.
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Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2006.Robert McKeon, Committee Member ; Robert Lee, Committee Member ; Robert Guldberg, Committee Member ; Ravi Bellamkonda, Committee Member ; Michelle LaPlaca, Committee Chair. Vita.
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Irons, Hillary Rose. "Bone Marrow-Derived Mesenchymal Stem Cells As an Alternate Donor Cell Source for Transplantation in Tissue-Engineered Constructs After Traumatic Brain Injury." Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/16168.
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The incidence and long-term effects of traumatic brain injury (TBI) make it a major
healthcare and socioeconomic concern. Cell transplantation may be an alternative
therapy option to target prolonged neurological deficits; however, safety and efficacy of
the cells must be determined. Bone marrow-derived mesenchymal stem cells (MSCs)
are an accessible and expandable cell source which circumvent the many of the
accessibility and ethical concerns associated with fetal tissues. A major impediment to
recent clinical trials for cell therapies in the central nervous system has been the lack of
consistency in functional recovery where some patients receive great benefits while
others experience little, if any, effect (Watts and Dunnett 2000; Lindvall and Bjorklund
2004). There are many possible explanations for this patient-to-patient variability
including genetic and environmental factors, surgical techniques, and donor cell
variability. Of these, the most easily addressable is to increase the reproducibility of
donor cells by standardizing the isolation and pre-transplantation protocols, which is the
central goal of this dissertation. First, we present an animal study in which transplants of
MSCs and neural stem cells (NSCs) were given to brain-injured mice, however, the
efficacy of the treatment had high variability between individual subjects. Second, we
designed a method to produce MSC-spheres and characterize them in vitro. Last, we
employed an in vitro 3-D culture testbed as a pre-transplant injury model to assess the
effects of the MSC-spheres on neural cells. The electrophysiological function of the
uninjured testbed was assessed, and then MSC-spheres were injected into the testbed
and apoptosis of the host cells were measured. The results of this study contribute to our
understanding of how extracellular context may influence MSC-spheres and develop
MSCs as a donor cell source for transplantation.
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Hagevik, André. "Brainstem and spinal cord mechanisms that control locomotor activity in larval lamprey /." free to MU campus, to others for purchase, 1997. http://wwwlib.umi.com/cr/mo/fullcit?p9842533.
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Tripathi, Pratibha. "Isolation of multipotent astroglia form the adult stem cell niche and the injured brain." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-104224.
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Petropoulos, Demetrios. "An electrophysiological study of the brain stem neural networks controlling feeding behavior in lampreys." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0003/MQ44244.pdf.
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Petropoulos, Dēmētrios. "An electrophysiological study of the brain stem neural networks controlling feeding behavior in lampreys /." Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=20837.
Full textAbstract:
The objective of this study was to develop an in vitro model in lamprey, a lower vertebrate, for investigating the neural circuitry controlling feeding behavior. Microstimulation of the trigeminal afferents and some of the rhombencephalic regions that project to the trigeminal motor nucleus were shown to elicit excitatory synaptic responses in trigeminal motoneurons involving both AMPA/Kainate and NMDA receptors. Disynaptic glycinergic inhibition was also present in some cases. Interestingly, rhythmical membrane potential oscillations were elicited in trigeminal motoneurons upon stimulation of trigeminal afferents or the principal sensory nucleus. Low and high frequency oscillations were obtained which seem to represent fast and slow feeding rhythms previously described in lampreys in vivo. These oscillations represent the first evidence of centrally generated rhythmic activity that underlies feeding in lampreys.
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Schwarz, Stefan Theodor. "Magnetic resonance imaging correlates of neuronal degeneration of brain stem nuclei in Parkinson's disease." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/37023/.
Full textAbstract:
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by a loss of pigmented dopaminergic neurons in the substantia nigra (SN) pars compacta and loss of pigmented noradrenergic neurons in the locus coeruleus (LC). Diagnosing PD can be challenging, especially in the early stages particularly when the typical movement disorder symptoms such as tremor, rigidity, bradykinesia and postural instability are not easily identifiable. Despite well-established PD clinical diagnostic criteria there is a misdiagnosis rate of up to 15% by neurology specialists and 25 % by general practitioners. The only approved diagnostic test to confirm suspected PD in a tremulous patient is dopamine transporter single photon emission tomography (DaTScanTM). This test is costly (£800 – 1500 in the UK) and has limited geographical availability in the UK. It involves exposure to ionising radiation and can only be used to assess the integrity of the dopaminergic system. Therefore there is a strong need for better and more accessible diagnostic tests for PD. The aim of this thesis is to investigate the sensitivity and specificity of three different MRI techniques as potential biomarkers of PD. MRI at 3T field strength was used in this thesis to demonstrate PD pathology in the pigmented brain stem nuclei of SN, LC and the ventral tegmental area (VTA). The objective was to develop new, easily accessible and affordable disease markers to help clinicians to establish the correct diagnosis early. A promising technique, which is based on the assessment of free motion of water-associated protons in tissue, is termed diffusion tensor imaging (DTI). The amount of free motion in all directions of protons in tissues like the brain can be described using mean diffusivity (MD) as a measure. Diffusion in tissues like the brain is often limited (“restricted”) in certain directions. For example diffusion across the myelin sheaths of nerve-fibres in the brain white matter is constrained, whereas along the direction of the nerve fibre protons can diffuse freely. This is termed anisotropic diffusion and can be described using fractional anisotropy as a measure (FA). Microstructural PD pathological processes may alter these measures of diffusivity especially in the area of the early affected brain region of the SN. In a prospective case control study of 30 patients and 22 controls diffusion tensor imaging alterations of the SN were investigated by measuring regional alterations of fractional FA and MD. In addition, a systematic literature review and meta-analysis was performed to determine the evidence for nigral DTI alterations throughout the literature. The case control study did demonstrate a small but significant increase of nigral MD; however the meta-analysis did not confirm this result when synthesizing effect sizes of nine identified relevant studies. No significant PD induced FA alterations were found in the prospective case control study. The meta-analysis of nigral FA changes did likewise not show significant FA decrease after correcting for studies with unusual high FA measures in the control arm population. In summary the meta-analysis and the results of the case control study did not confirm that standard DTI measurements of the SN are reliable biomarkers of PD pathology. In a further case-control study MRI sequences tracking the neuromelanin content of the pigmented brain stem nuclei like the SN, LC and the ventral tegmental area were investigated. PD induced decline of neurons in these nuclei causes depigmentation due to loss of neuromelanin content. In this study (including data from 24 PD patients and 20 controls) I found that only little neuromelanin related signal could be observed in the ventral tegmental area and there was no significant difference between patients with PD and controls. However, there were significant signal alterations of the SN and LC signal when comparing between the two groups. The neuromelanin related signal loss was most pronounced in the posterior SN even in the earlier stages of the disease. The signal loss in the anterior SN was less severe and correlated with the unified PD rating scale (UPDRS) and Hoehn and Yahr score as a measure of disease severity. The neuromelanin related signal reduction was significant but less extensive in the region of the LC when compared to the SN. The signal alterations in the LC did not correlate with the UPDRS or the Hoehn and Yahr score. In the third part of the experimental section of this thesis, a further prospective case-control study of 19 participants (10 patients with PD) and retrospective study of 105 clinical cases (9 patients with PD) was performed. A high resolution SWI/T2* ‘iron sensitive’ sequence was used to assess MRI changes of the nigrosome-1. Nigrosomes are little islands of dopaminergic cells with physiologically low iron content. The healthy hyperintense signal of the linear shaped nigrosome-1 surrounded by the iron containing low signal SN regions has great resemblance to the appearance of a swallow tail. The PD induced pathological signal reduction within nigrosome-1 resulted in a loss of the typical ‘swallow tail appearance’. Visual qualitative assessment of the MRI scans for absence and presence of nigrosome-1 revealed high sensitivity and specificity (80-100% and 86-89% respectively) to allow differentiation of PD from healthy controls and non-PD patients. In summary I found that standard nigral DTI is not reliable as a PD biomarker. Nigrosome and neuromelanin weighted MRI offers great potential for development into a clinically useful biomarker. Comparing the two techniques, nigrosome imaging has some advantages over neuromelanin weighted imaging: the high resolution SWI/T2* sequence is shorter (2-5 min versus 7-14 min neuromelanin MRI. However, further optimization of neuromelanin MRI sequences may be able to shorten the acquisition time. A further advantage of nigrosome MRI is that the images can be visually assessed for pathological alterations without the need for complicated analysis or data processing. A disadvantage of high resolution SWI/T2* is that it is more prone to artefacts. An advantage of neuromelanin weighted MRI is that changes especially in the anterior substantia nigra correlate to measures of disease severity like the UPDRS, although there is some early evidence from pilot studies that nigrosome imaging (at field strengths of 7T) may also be useful to assess disease severity related changes. Which of the two techniques is better suited to monitor longitudinal progressive PD related changes has to be assessed in future studies. In conclusion standard nigral DTI measures have no proven value as a reliable diagnostic marker of PD. High resolution T2*/SWI MRI and neuromelanin weighted MRI of PD induced alteration of pigmented brain stem neurons distinguish PD from non-PD and control subjects with high sensitivity and specificity. Neuromelanin related alterations especially of the anterior SN correlate to disease severity measures like the UPDRS and therefore have potential as disease progression marker. The easy applicability of the ‘swallow tail sign’ to indicate a healthy nigrosome-1 in the SN may well prove a useful marker to help the clinical diagnosis of PD. If future studies confirm a similar diagnostic accuracy as the current clinical gold standard DaTScanTM, nigrosome MRI may replace DaTScanTM in the standard clinical setting.
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Sevilla, Cruz Jr. "Long-term Effects of Notch1 Signaling on Neural Stem Cells following Traumatic Brain Injury." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5918.
Full textAbstract:
Traumatic brain injury (TBI) is a devastating problem which stands as a leading cause of death and disability. The elderly is significantly affected by TBI, typically as the result of falls, and recovery is especially limited. This, in part, is associated with decreased tissue-specific stem cell regeneration and replacement of damaged cells in the aged brain. The diminished ability of the aged brain to recover is especially devastating after TBI, likely leading to permanent loss of sensory, motor, and cognitive functions. Studies have shown that the mature mammalian brain contains Neural Stem Cells (NSCs), found in specific regions of the brain, which can generate functional neurons during normal and pathological conditions. Two of those regions, the Dentate Gyrus (DG) of the hippocampus as well as the Subventricular Zone (SVZ) of the lateral ventricles, have proven to be niches for these multipotent NSCs. A key regulator in the maintenance of these NSCs is the Notch signaling pathway, shown to control proliferation, differentiation, and apoptosis of NSCs during development and throughout adulthood. In the current study, we assessed the regulatory mechanisms that drive the regenerative functions of NSCs in a neuropathological state following TBI. Using the Lateral Fluid Percussion Injury model, we analyzed the diffuse effects of the injury response on 3-month old male Sprague-Dawley rats. Immediately following TBI, Notch agonist, antagonist or vehicle was infused into the lateral ventricle for 7 days to assess the role of Notch signaling on neural stem cell proliferation/survival and neurogenesis at 30 days post-TBI. Dividing cells during infusion time were labeled with BrdU via single daily intraperitoneal injections for 7 days. Animals were sacrificed at 30 days post-injury and brain tissues were processed then immunolabeling for BrdU and Doublecortin. We found a higher number of BrdU-positive cells in the FPI+Notch1 agonist group when compared to Sham and FPI+Jagged-1 Fc antagonist groups in the contralateral granular zone. A significant increase in proliferation/survival was also seen in FPI+Notch1 versus Sham/FPI+Jagged-1 Fc and for FPI+Vehicle versus Sham animals in both the ipsilateral and contralateral hilus. DCX immunolabeling did not establish a significant difference in FPI+Notch1 compared to Sham animals, nor across any other groups, which is consistent with what we know of activation of the Notch pathway. Our results demonstrate that Notch1 signaling is directly involved in cellular proliferation/survival of NSCs in the DG following TBI at 30 days post-injury, but further work must be done to understand the fate of these cells. Thus, drug treatment targeting Notch1 signaling could serve as a potential therapeutic target following TBI to preserve NSCs and limit long-term cognitive deficits.
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Yulius, Hermanto. "Transplantation of feeder-free human induced pluripotent stem cell-derived cortical neuron progenitors in adult male Wistar rats with focal brain ischemia." Kyoto University, 2019. http://hdl.handle.net/2433/242389.
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Rivera, Maricruz. "MOLECULAR MECHANISMS OF STRESS RESPONSE IN BRAIN CANCER." Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1445956088.
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Leung, Ka-kit Gilberto, and 梁嘉傑. "Applications of self-assembling peptide nanofibre scaffold and mesenchymal stem cell graft in surgery-induced brain injury." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206347.
Full textAbstract:
Surgery-induced brain injury (SBI) refers to trauma caused by routine neurosurgical procedures that may result in post-operative complications and neurological deficits. Unlike accidental trauma, SBI is potentially subject to preemptive interventions at the time of surgery. SBI can cause bleeding, inflammation and the formation of tissue gaps. Conventional haemostatic techniques, though effective, are not necessarily conducive to healing. Inflammation and the absence of extracellular matrix in tissue gaps also hinder regeneration after SBI. This study investigated the applications of RADA16-I, a type I self-assembling peptide nanofibre scaffold (SAPNS), and mesenchymal stem cells (MSCs) in the treatment of SBI. Using animal SBI models, treatments were applied immediately and locally onto the operative fields, taking advantages of the haemostatic and cell-carrying properties of RADA16-I, the immune- modulatory effects of MSCs, and the earliest available therapeutic window for SBI.
There were three objectives. Objective 1 was to compare RADA16-I with conventional haemostatic methods, including electrocautery and fibrin sealant, in their effects on the brain’s acute cellular inflammatory response. The hypothesis was that RADA16-I would cause the same or a lesser degree of inflammation. This study showed that RADA16-I was superior to electrocautery, and was noninferior to conventional topical haemostats.
Objective 2 was to study the in vitro expansion of MSCs within RADA16-I in preparation for in vivo transplantation. The hypothesis was that the in vitro survival of MSCs would vary between different RADA16-I concentrations and culturing methods. This study showed that plating MSCs onto pre-buffered RADA16-I would protect the cells against RADA16-I’s intrinsic acidity and result in better initial survival. Subsequent integration with the RADA16-I hydrogel, however, was poor. Mixing the cells directly with RADA16-I caused initial cell loss but allowed better integration. RADA16-I at lower concentrations resulted in better survival but also more fragile hydrogels that were mechanically unfit for transplantation. Mixing MSCs with 0.5% RADA16-I for seven days represented a compromise between these competing factors.
Objective 3 was to study the in vivo effects of a MSC-RADA16-I implant on tissue reactions after SBI. The hypothesis was that the combinatorial therapy would result in less cellular inflammatory response than MSC alone or RADA16-I alone. Implants of pre-buffered 0.5% RADA16-I hydrogel, with or without cells, were found to cause less inflammation than control. MSCs in free suspension resulted in significantly more pronounced inflammation than when carried in RADA16-I. Supplementing RADA16-I with MSCs, however, did not confer additional benefit over RADA16-I alone.
The present study provided new preclinical evidence to support future clinical testing of RADA16-I as a novel surgical haemostat. It also demonstrated the feasibility of early intracerebral transplantation of RADA16-I hydrogel in the treatment of SBI. Whether RADA16-I and/or transplanted MSCs could modulate the brain’s inflammatory response after SBI require further investigations, which may include the search for the optimal ex vivo expansion technique and specifically tailored nanofibre scaffold. The translational applications of these findings would include the treatment of SBI over critical brain regions where trauma would cause severe functional deficits and where better healing would facilitate patient recovery.published_or_final_version
Anatomy
Doctoral
Doctor of Philosophy
39
Pollini, Daniele. "Pleiotropic effect of MATR3 in pluripotent stem cells." Doctoral thesis, Università degli studi di Trento, 2020. http://hdl.handle.net/11572/276211.
Full textAbstract:
Matrin3 (MATR3) is an RNA binding protein involved in many roles in the nucleus, such as chromatin architecture and gene expression regulation, modulating transcriptional and post-transcriptional processes as RNA splicing and mRNA stabilization. Nevertheless, some functions of MATR3 within the cells are not entirely clear. MATR3 has been associated with Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease that damages motor neuron (MN) cells and leads to progressive muscle paralysis and respiratory failure. A better understanding of MATR3 activity within cell physiology could represent an essential breakthrough for studying MATR3-associated pathologies. Using MATR3-silenced human pluripotent stem cell (hiPSC) line model, we collected data on the MATR3 role in the pluripotency and in the neural induction and differentiation. We found that the downregulation of MATR3 alters the expression level of crucial self-renewal factors such as OCT4, NANOG, KLF4, and LIN28A. We observed MATR3 acts at multiple levels of the gene expression, i.e. regulating YTHDF1 expression, and in RNA metabolism, having a role in mRNA stabilization and translation. The reduction of stemness potential caused by MATR3 downregulation creates a defect during the neurodifferentiation process, which does not arrest motor neurons formation but induces selective alterations that may affect motor neurons functionality. Indeed, several morphological and molecular abnormalities were observed during the neuronal differentiation, such as the alterations of the formation of neuroepithelial rosettes that arise in a reduction of neurite lengths and arborization in neuronal cells. On this basis, we investigated neuronal differentiation in the brain organoids grown from iPSCs derived from ALS patients fibroblasts. We show, for the first time, that MATR3 is a critical factor in orchestrating the stemness network through transcriptional, post-transcriptional, and translational regulation, therefore affecting the differentiation of mature neurons.
40
Pollini, Daniele. "Pleiotropic effect of MATR3 in pluripotent stem cells." Doctoral thesis, Università degli studi di Trento, 2020. http://hdl.handle.net/11572/276211.
Full textAbstract:
Matrin3 (MATR3) is an RNA binding protein involved in many roles in the nucleus, such as chromatin architecture and gene expression regulation, modulating transcriptional and post-transcriptional processes as RNA splicing and mRNA stabilization. Nevertheless, some functions of MATR3 within the cells are not entirely clear. MATR3 has been associated with Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease that damages motor neuron (MN) cells and leads to progressive muscle paralysis and respiratory failure. A better understanding of MATR3 activity within cell physiology could represent an essential breakthrough for studying MATR3-associated pathologies. Using MATR3-silenced human pluripotent stem cell (hiPSC) line model, we collected data on the MATR3 role in the pluripotency and in the neural induction and differentiation. We found that the downregulation of MATR3 alters the expression level of crucial self-renewal factors such as OCT4, NANOG, KLF4, and LIN28A. We observed MATR3 acts at multiple levels of the gene expression, i.e. regulating YTHDF1 expression, and in RNA metabolism, having a role in mRNA stabilization and translation. The reduction of stemness potential caused by MATR3 downregulation creates a defect during the neurodifferentiation process, which does not arrest motor neurons formation but induces selective alterations that may affect motor neurons functionality. Indeed, several morphological and molecular abnormalities were observed during the neuronal differentiation, such as the alterations of the formation of neuroepithelial rosettes that arise in a reduction of neurite lengths and arborization in neuronal cells. On this basis, we investigated neuronal differentiation in the brain organoids grown from iPSCs derived from ALS patients fibroblasts. We show, for the first time, that MATR3 is a critical factor in orchestrating the stemness network through transcriptional, post-transcriptional, and translational regulation, therefore affecting the differentiation of mature neurons.
41
Slee, Sean Joseph. "Intrinsic and synaptic mechanisms underlying sound localization in the avian auditory brainstem /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/10556.
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Stephenson, Mark Ray. "Human auditory brainstem response to dichotic click stimuli /." The Ohio State University, 1986. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487267546983858.
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Ene, Chibawanye Isidore. "Relevance of histone 3 lysine 27 modifiers in neural stem cells and malignant brain tumours." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610540.
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Xiong, Anqi. "Novel Regulators of Brain Tumor Development : – From neural stem cell differentiation to in vivo models." Doctoral thesis, Uppsala universitet, Institutionen för immunologi, genetik och patologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-264470.
Full textAbstract:
Malignant brain tumors are diseases with poor prognosis and/or severe long-term side effects of treatment. This thesis aimed to discover novel regulators in brain tumor development, based on studying neural stem cell and progenitor cell (NSPC) differentiation and using animal models to introduce new insights to mechanisms of human brain tumors. The enzyme heparanase (HPSE) that degrades heparan sulfate (HS) is active in cell signaling and ECM remodeling. In paper I, we found an enhanced differentiation to oligodendrocytes in ES cell-derived NSPCs overexpressing HPSE. Further analysis suggested that this enhanced formation of oligodendrocytes was associated with alterations in receptor tyrosine kinase signaling, and that HPSE might also exert anti-apoptotic functions. Subsequently, in paper II we studied the involvement of HPSE in glioma development. We observed that high HPSE levels associated with poor survival in glioma patients. In experimental models, we found that HPSE promoted glioma growth, and that an inhibitor of HPSE reduced glioma progression both in vitro and in vivo. We hypothesize that regulators in NSPC differentiation could have a potential role in brain tumor development. In paper III, we explored the function of NRBP2, a pseudokinase that is up-regulated during NSPC differentiation. We found low expression of NRBP2 in brain tumors, in comparison to normal brain. In medulloblastoma, in particular, low NRBP2 expression is linked to poor prognosis. Overexpression of NRBP2 in medulloblastoma cells led to impaired cell growth and migration, concomitant with an increased cell death. In paper IV, we searched for novel glioma susceptibility genes by sequencing dog breeds from the same ancestor but with different glioma incidence. In this way we identified three new glioma-associated genes. Two of these are significantly regulated in human glioma and one of those might have a role in glioblastoma stem cell differentiation.
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Barrett, Andrea Lynn. "A FGF-Hh feedback loop controls stem cell proliferation in the developing larval brain of drosophila melanogaster." [College Station, Tex. : Texas A&M University, 2007. http://hdl.handle.net/1969.1/ETD-TAMU-2017.
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Masilela, Sibonisiwe Ntini. "Effects of nicotine on content of corticotropin releasing factor (CRF) in rat amygdala, hypothalamus and brain stem." Morgantown, W. Va. : [West Virginia University Libraries], 1999. http://etd.wvu.edu/templates/showETD.cfm?recnum=487.
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Thesis (M.S.)--West Virginia University, 1999.Title from document title page. Document formatted into pages; contains viii, 138 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 105-134).
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Monsivais, Pablo. "GABAergic inhibition of nucleus magnocellularis and laminaris by the superior olivary nucleus /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/10635.
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Tate, Matthew C. "The development of extracellular matrix based neural stem cell transplants for treatment of traumatic brain injury." Diss., Georgia Institute of Technology, 2002. http://hdl.handle.net/1853/20166.
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Uyar, Ramazan [Verfasser], and Rainer [Akademischer Betreuer] Glaß. "Glioma-associated mesenchymal stem cells have profound effects on brain tumors / Ramazan Uyar ; Betreuer: Rainer Glaß." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1202011683/34.
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Hatcher, Kevin. "Use of EEG to Understand Brain Intensity in Engineering Students Using a Stem Educational Mobile Application." Wright State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=wright1463148705.
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