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1
Peden, Carol J. "Proton and phosphorus spectroscopy of hypoxic, ischaemic and haemorrhagic perinatal brain injury." Thesis, University of Edinburgh, 1996. http://hdl.handle.net/1842/21460.
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Proton magnetic resonance spectroscopy was investigated as a non-invasive technique to observe biochemical changes in the brains of children who had sustained perinatal hypoxic, ischaemic and haemorrhagic brain injury. Methods: Proton spectra were acquired from the centre of the brain in premature infants, and from the parieto-occipital region in older children. Phosphorus spectra were also collected and compared with the proton spectra. Unlocalized phosphorus spectra were acquired at different repetition times. Some children had localized phosphorus spectroscopy examinations with two and four dimensional chemical shift imaging. The children were between 33 weeks post-conceptional age and four years and three months postnatal age at the time of their initial spectroscopy examination. The ability of early proton spectroscopy to predict outcome was considered in relation to the clinical neurological state at eighteen months or more. Because certain assumptions were made about the proton spectra (e.g. no T2 measurements were made), proton spectra were acquired from adults with central nervous system tumours. At surgery, biopsies were taken from the tumours and from normal brain and were analysed with in vitro spectroscopy, histology and established biochemical techniques. The metabolite ratios were compared with those from the in vivo spectra. Modifications were made to commercially available monitoring and ventilation equipment to provide the same standards of care within the magnetic field for sick patients, as on the neonatal or intensive care units. Results: All the proton spectra had peaks attributable to N-Acetyl aspartate (NAA), choline containing compounds (Cho) and creatine plus phosphocreatine (Cr). The NAA/Cho and NAA/Cr peak height ratios increased with age, while the Cho/Cr ratio decreased. The NAA/Cr ratios were significantly decreased in all children with an abnormal neurological outcome when compared with the NAA/Cr ratios from children with a normal outcome. The NAA/Cho ratios were significantly decreased in those children with a moderate outcome but not in those with a severe neurological outcome. There were no significant changes in the Cho/Cr ratios. The phosphorus spectra showed changes; phosphocreatine (PCr) to inorganic phosphate (Pi) decreased after injury and there was a marked increase in pH in the children with the poorest outcome. The apparent Tl of Pi was increased in the first month after birth in the children with a severe outcome. Few changes were seen with localized phosphorus spectroscopy in children who had focal lesions. Phosphorus spectra returned to normal within weeks of birth, while the proton spectra remained abnormal. The adult tumour proton spectra compared well with the in vitro spectra and histology of the biopsies. The concentrations changes of metabolites in vivo, were consistent with the measurements made with established biochemical techniques. Discussion: Hypoxic-ischaemic injury produced changes in the proton spectrum from neonatal brain. These changes persisted with time. Some of these changes correlated with outcome. Phosphorus spectra showed acute changes in response to injury, but the changes resolved within weeks. NAA is located in neurons; the decrease in NAA could be due to failure of neurons to develop normally, or to areas of neuronal loss and gliosis resulting from hypoxic-ischaemic damage. Phosphorus spectra may return to normal because neurons and glia have similar phosphorus metabolite ratios. Proton spectroscopy combined with magnetic resonance imaging, may become a useful technique for studying the anatomy and biochemistry of the brain in children who have suffered brain injury.
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Pennell, Craig Edward. "The role of lactate measurement in the prediction of fetal hypoxic-ischaemic brain injury during labour." University of Western Australia. School of Women's and Infants' Health, 2004. http://theses.library.uwa.edu.au/adt-WU2003.0037.
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[Truncated abstract] In this thesis the role of lactate measurement has been evaluated in intrapartum assessment of fetal wellbeing. Specifically, I have addressed the question of whether fetal lactate measurement is better than the assessment of fetal heart rate patterns or the measurement of pH at predicting fetal brain injury after intrapartum asphyxia. Using an ovine model of repeated umbilical cord occlusion designed to mimic events which may occur during human labour, I have shown that the measurement of fetal lactate levels after repeated cord occlusion is significantly associated with the severity of brain injury after the asphyxial insult. No significant associations were identified with fetal pH measurements or with the duration of decelerative or compound fetal heart rate patterns; however, this is the first study to describe an association between the duration of both increased fetal heart rate variability and fetal heart rate overshoot with the severity of subsequent brain injury. Although no significant association was identified between fetal arterial pressure measured between umbilical cord occlusions and the grade of brain injury, the studies performed in this thesis are the first to show a strong correlation between the duration of specific arterial pressure responses during cord occlusions and the grade of brain injury, accounting for approximately 90% of the variability seen in the severity of injury. The mechanism responsible for the improved ability of lactate measurement to predict fetal brain injury is unknown. It may be because fetal lactate levels are a more stable marker of anaerobic metabolism of glucose than fetal pH levels, which are influenced by both increasing levels of carbon dioxide and anaerobic metabolism of amino-acids and fatty acids. In addition fetal pH levels can be rapidly normalised through placental exchange of carbon dioxide whereas fetal lactate levels are slow to normalise across the placenta as they rely on facilitated diffusion.
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Wilkinson, Dominic James Clifford. "Ethical issues in the use of magnetic resonance imaging of the brain in newborn infants with hypoxic-ischaemic encephalopathy : neuroimaging and decision-making for brain injured newborns." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:d61e4318-3568-4310-bf92-c7d70f2cb3da.
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Infants with hypoxic-ischaemic encephalopathy (birth asphyxia) have a high risk of death or disability. Those with poor prognosis are sometimes allowed to die after withdrawal of intensive care. In recent years, doctors have used new types of brain scan, magnetic resonance imaging (MRI), to predict the type and severity of impairment if the infant survives and to help with such decisions. In this thesis, I analyse the issues arising from the use of MRI for prognostication and decision-making in newborn infants. I argue that previous prognostic research has been hampered by a failure to identify and focus on the most important practical question and that this contributes to uncertainty in practice. I outline recommendations for improving research. I then look at existing guidelines about withdrawal of life-sustaining treatment. I identify several problems with these guidelines; they are vague and fail to provide practical guidance, they provide little or no genuine scope for parental involvement in decisions, and they give no weight to the interests of others. I argue that parental interests should be given some weight in decisions for newborn infants. I develop a new model of decision-making that, using the concept of a Restricted Life, attempts to set out clearly the boundaries of parental discretion in decision-making. I argue that where infants are predicted to have severe cognitive or very severe physical impairment parents should be permitted to request either withdrawal or continuation of treatment. I justify this model on the basis of overlapping interests, (prognostic, experiential and moral) uncertainty, asymmetrical harms, and the burden of care. In the conclusion, I set out a guideline for the use of MRI in newborn infants with hypoxic-ischaemic encephalopathy. I suggest that this guideline would provide a more robust, coherent and practical basis for decision-making in newborn intensive care.
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Fairlie, John. "Neuronal and microvascular adaptions to hypoxic/ischaemic injury in animal models." Thesis, University of Newcastle Upon Tyne, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427287.
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Flynn, Liam Martin Clint. "Physiological responses to brain tissue hypoxia and blood flow after acute brain injury." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31268.
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This thesis explores physiological changes occurring after acute brain injury. The first two chapters focus on traumatic brain injury (TBI), a significant cause of disability and death worldwide. I discuss the evidence behind current management of secondary brain injury with emphasis on partial brain oxygen tension (PbtO2) and intracranial pressure (ICP). The second chapter describes a subgroup analysis of the effect of hypothermia on ICP and PbtO2 in 17 patients enrolled to the Eurotherm3235 trial. There was a mean decrease in ICP of 4.1 mmHg (n=9, p < 0.02) and a mean decrease in PbtO2 (7.8 ± 3.1 mmHg (p < 0.05)) in the hypothermia group that was not present in controls. The findings support previous studies in demonstrating a decrease in ICP with hypothermia. Decreased PbtO2 could partially explain worse outcomes seen in the hypothermia group in the Eurotherm3235 trial. Further analysis of PbtO2 and ICP guided treatment is needed. The third chapter focuses on delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH), another form of acute brain injury that causes significant morbidity and mortality. I include a background of alpha-calcitonin gene-related peptide (αCGRP), a potential treatment of DCI, along with results from a systematic review and meta-analysis of nine experimental models investigating αCGRP. The meta-analysis demonstrates a 40.8 ± 8.2% increase in cerebral vessel diameter in those animals treated with αCGRP compared with controls (p < 0.0005, 95% CI 23.7 to 57.9). Neurobehavioural scores were reported in four publications and showed a Physiological responses to brain tissue hypoxia and blood flow after acute brain injury standardised mean difference of 1.31 in favour of αCGRP (CI -0.49 to 3.12). I conclude that αCGRP reduces cerebral vessel narrowing seen after SAH in animal studies but note that there is insufficient evidence to determine its effect on functional outcomes. A review of previous trials of αCGRP administration in humans is included, in addition to an original retrospective analysis of CSF concentrations of αCGRP in humans. Enzyme-linked immunosorbent assay of CSF (n = 22) was unable to detect αCGRP in any sample, which contrasts with previous studies and was likely secondary to study methodology. Finally, I summarise by discussing a protocol I designed for a dose-toxicity study involving the intraventricular administration of αCGRP to patients with aSAH and provide some recommendations for future research. This protocol was based upon the systematic review and was submitted to the Medical Research Council's DPFS funding stream during the PhD.
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Rutherford, Mary. "Magnetic resonance imaging of hypoxic-ischaemic brain lesions in the term infant." Thesis, University of Bristol, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262817.
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Lim, Ta. "The role of hypoxia-inducible factor-1α in xenon preconditioning versus hypoxic-ischaemic organ injury." Thesis, Imperial College London, 2008. http://hdl.handle.net/10044/1/7663.
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Background: The anaesthetic gas xenon provides long-lasting preservation of neuronal function when given several hours prior to neuronal injury. This phenomenon is described as preconditioning. However, little is known of the mechanisms by which xenon preconditioning mediates its protective effect. Interest has focused on the involvement of hypoxia-inducible factor-1α (HIF-1α) in preconditioning because: (i) Hypoxia activates HIF-1α and is an effective preconditioning stimulus; (ii) HIF-1α is a regulator of adaptive responses promoting cellular survival; (iii) Several genes that have hypoxia-responsive elements (HRE) for HIF-1 in the promoter region are capable of mediating preconditioning (e.g., erythropoietin). Therefore, this study speculates on the role of HIF-1α in xenon preconditioning. Method: Separate cohorts of male adult C57/BL6 mice were preconditioned by exposure to 75% xenon/25 % oxygen for 2 hours and thereafter immediately sacrificed for organ harvesting at 0-24 hours after xenon preconditioning. Semi-quantitative study of HIF-1α and EPO protein expression was performed by Western blot analysis, and RT-PCR was used as a measure of gene transcription. Results: Xenon preconditioning provokes a time-dependent increase in HIF-1α protein in brain as well as kidney. Xenon preconditioning also caused a time-dependent increase in EPO (a HIF-1 target gene) transcription and protein expression in a corresponding time course to xenon-induced HIF-1α. To elucidate the mechanisms of xenon-induced HIF-1α accumulation, the effect of xenon preconditioning on HIF-1α transcription, translation and degradation was studied. Xenon preconditioning does not induce a change in HIF-1α mRNA expression, nor does it significantly attenuate the expression of the PHD2 enzyme, required for HIF-1α degradation. To explore translation-dependent pathways, mice were treated with rapamycin before xenon preconditioning, to inhibit translation of HIF-1α through the mTOR pathway. Inhibition of this pathway prevented the xenon-induced increase of HIF-1α protein. To ascertain whether HIF-lα is required for xenon preconditioning, siRNA was used to knockdown HIF-lα expression in the kidney and xenon's renoprotective properties were shown to be abolished. Conclusions: Over the same time course as xenon's protection against subsequent injury in both brain and kidney, xenon preconditioning induces expression of HIF-1α. Increased HIF-1α expression is also associated with increased activity as evidenced by enhanced transcription and translation of the downstream effector, EPO. Xenon preconditioning does not regulate HIF-1α at the transcriptional level, nor does it inhibit HIF-lα degradation. However, these results suggest that xenon preconditioning upregulates expression of HIF-1α through translation-dependent mechanisms. Furthermore, xenon's action on HIF-1α is shown to be causally related to its organ protective effect. If these data can be extrapolated to the clinical setting, exposure to xenon would be beneficial prior to procedures in which organ perfusion is interrupted, preventing hypoxic-ischaemic as well as ischaemic-reperfusion injury.
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Whiteley, Tara. "Mitochondria and secondary ischaemic neural injury after head trauma." Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285401.
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Rocha, Ferreira E. "The role of infection/inflammation, the TNF family of cytokines and myeloid cells in perinatal hypoxia-ischaemia brain injury." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1447553/.
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Synergy between materno-foetal infection and hypoxic-ischaemic insult around the time of birth is a known contributing factor to perinatal brain damage. This is a common precursor to cerebral palsy and other neurological deficits, affecting 2 to 5 per 1000 live births. Endotoxin up-regulates several molecules, including the TNF cluster of pro-inflammatory cytokines. Our group has explored the role of this cluster and shown that its deletion abolishes LPS sensitization to neonatal hypoxic-ischaemic insult. In this study we wanted to first investigate the effects of LPS-mediated sensitization across multiple wild type strains (C57BL/5, 129SVJ, BALB/c, CD1 and FVB) in order to then further characterize the TNF cluster, by studying the individual effects of TNFα, LTα and LTβ members of this cluster, using either global gene deletion, or peripheral myeloid/macrophage-specific deletion of the floxed TNFα allele with MLys::Cre (MLys+). Additionally, we decided to also look at the acquired cellular immune system, using the athymic nude mouse model of T cell deficiency (nu). At P7, littermates for each of the wild type strains, wild-type and homozygous knock-out offspring of heterozygous animals listed above underwent hypoxic-ischaemic insult, consisting of unilateral carotid occlusion followed 2 hours recovery before being placed in a hypoxic chamber for 30min with continuous 8% oxygen exposure. 12 hours prior, animals received a single intraperitoneal injection of 0.6µg/g LPS or saline as a control. 1/3 of animals in the wild type strains group underwent hypoxia-ischaemia alone as a control for saline treatment. LPS pre-treatment resulted in substantial increase inflammation, neuronal injury and infarct in all wild type strains, as well as in the phenotypically wild type littermates of the homozygous mutant animals. Mice lacking both copies of the LTα gene revealed a clear reduction in LPS-mediated sensitization. In reverse, global deletion of LTβ had a detrimental effect, with significant increase in brain damage. Global deletion of TNFα showed a trend towards greater damage, but deletion just in MLys+ macrophages was strongly protective, pointing to a dual role for the TNFα gene depending on in which cell-type it is expressed. Finally, nude animals (nu/nu) demonstrated a complete lack of LPS-mediated sensitization to subsequent hypoxic-ischaemic insult, suggesting that LPS sensitization may require T cell function.
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Crooks, Suzanne. "Long-term neuropsychological and psychosocial outcomes of hypoxic-ischemic brain injury." Thesis, Queen's University Belfast, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.676279.
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Purpose: This study aimed to identify the long-term cognitive impairments arising from Hypoxic Ischaemic Brian Injury (HIBI) in a group of patients at least one year post insult. The long term psycho-social impact and carer burden associated with HIBI were also investigated. Method: A case series design was employed to facilitate detailed analysis of individual profiles. A battery of neuropsychological measures was administered to all participants. Cognitive domains assessed included premorbid and current IQ, visual and auditory recognition, immediate and delayed recall, auditory and visual attention, divided attention, executive functioning and visuo-spatial ability. HIBI survivors and a nominated family member also completed questionnaires relating to depression, anxiety, quality of life and caregiver strain. Results: Participants performed largely within estimated levels of premorbid functioning and any impairment was distributed across domains. Clinically significant symptoms of depression and anxiety were reported in both carers and HIBI smvivors and the carers' response suggested a high level of strain associated with caring. Conclusions: Results provide further support for the HIBI- bimodal distribution hypothesis. The use of premorbid measures and the inclusion of a caregiver assessment in neurorehabilitation interventions are indicated.
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Fu, Wai. "In silico prediction of cis-regulatory elements of genes involved in hypoxic-ischaemic insult." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36986896.
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Dobrucki, Wawrzyniec L. "Nitrogen and Oxygen Radicals in Ischemic and Hypoxic Injury of the Brain." Ohio University / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1057171850.
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Fu, Wai, and 符慧. "In silico prediction of cis-regulatory elements of genes involved in hypoxic-ischaemic insult." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B36986896.
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Widerøe, Marius. "Magnetic Resonance Imaging of Hypoxic-Ischemic Brain Injury Development in the Newborn Rat." Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for laboratoriemedisin, barne- og kvinnesykdommer, 2012. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-17210.
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Manderino, Lisa M. "Cognitive Functioning Under Hypoxic Stress in Individuals with History of Mild Traumatic Brain Injury." Kent State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=kent1591713552152285.
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Leonardo, Christopher C. "The Role of Extracellular Matrix and Matrix-Degrading Proteases in Neonatal Hypoxic-Ischemic Injury." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002587.
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Mathur, Manik. "The Blood-Brain Barrier integrity and function in ischaemic injury and multiple sclerosis with role of hypothermia." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/37404/.
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Background Brain injury following transient or permanent focal cerebral ischaemia matures from a multifaceted succession of pathophysiological events that progress in time and space. The key biochemical events related with these pathologies include excessive cytoskeletal remodeling, modulation of tight junction proteins, induction of oxidative stress and excessive release of pro-inflammatory cytokines. In addition, other neuropathologies such as multiple sclerosis have been shown to account for the development of these events and the consequent disruption of human blood-brain-barrier (BBB) integrity and function. However this study emphases on potentially new avenues of treatment which can protect the integrity of the blood-brain barrier and decrease post ischaemic consequences such as vasogenic oedema. Hypothermia has been hypothesised as a potent neuroprotectant and its putative effects have been assessed in the present research work. Objectives This thesis focuses on the putative role of hypothermia during intra- and post-ischaemic stroke mimicked by oxygen-glucose deprivation and followed by reperfusion. The impact of hypothermia has been studied on various inflammatory pathways such as pro-inflammatory cytokine levels, rate of apoptosis, extent of cytoskeleton remodeling and integrity and function of the BBB. In addition, we have also focused on the neuroinflammatory effects of multiple sclerosis (MS) on the BBB integrity. Method To mimic ischaemic insult, human brain microvascular endothelial cells, human astrocytes and human pericytes were exposed to oxygen-glucose deprivation (OGD) for 4 and 20 hours in the absence or presence of hypothermia (intra-ischaemic episode) and 4 hours of OGD followed by 20 hours of reperfusion in the presence of hypothermia (post-ischaemic episode) and cells left untreated were served as controls. Similarly, to assess BBB properties, all three cells were cultured simultaneously to establish an in vitro model of human BBB before exposing them to the experimental conditions. The integrity and function of triple cultures were measured via transendothelial electrical resistance (TEER) and paracellular flux via permeability markers such as sodium fluorescein (NaF) and Evan’s blue-labelled albumin (EBA). Various inflammatory inhibitors were also used during the insult to assess the distortion of the barrier. Furthermore, the triple cultures were exposed to multiple sclerosis patients’ serum mainly to study the neuroinflammatory effects. Moreover, with help of specific enzyme-linked immunosorbent assay-based kits pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-1β were measured during intra- and post-ischaemic episodes in the absence or presence of moderate hypothermia. Lastly, to evaluate the status of oxidative stress during acute ischaemic insult, the levels of superoxide anion generation and NADPH oxidase activities were measured. Results This study shows that moderate hypothermia significantly decreases pro-inflammatory cytokine levels when introduced during intra- and post-ischaemic episodes. Additionally, moderate hypothermia also maintains the BBB integrity and function during intra-and post-ischaemic scenarios. As evidenced by significant increase in resistance across the barrier and by concurrent decrease paracellular flux values. In addition, moderate hypothermia manages to reduce the oxidative stress impact during intra- and post-ischaemic episodes as documented by a decrease in NADPH oxidase and superoxide anion levels. Furthermore, the outlined study shows that MS patients’ serum is fortified with various inflammatory components such as pro-inflammatory cytokines, increase rate of apoptosis and resulting in destruction of the BBB architecture. Conclusions In this study, we have found moderate hypothermia to be a robust neuroprotectant in during intra- and post-ischaemic episodes of ischaemic injury mimicked by oxygen-glucose deprivation alone or followed by reperfusion. If adequately and appropriately maintained, moderate hypothermia may be an effective therapeutic option with minimal adverse effects. Furthermore, MS associated BBB destruction shows a new conduit for future research.
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Ranasinghe, Himani Sumudumalee. "Mechanisms underlying hypoxic ischemic injury to the developing brain: The significance of matrix metalloproteinase 2 and 9." Thesis, University of Auckland, 2009. http://hdl.handle.net/2292/4962.
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Perinatal hypoxic ischemic (HI) injury is a leading cause of long-term neurological complications in newborn babies. Matrix metalloproteinases (MMPs) are a family of endopeptidases that are capable of degrading the extracellular matrix (ECM) components. They are considered to be integral in many physiological processes. However, recently it has been demonstrated that the inappropriate activity of these proteases, particularly MMP-2 and 9, contribute to the pathogenesis of cerebral ischemia in the adult brain. Given that ECM disruption is frequently observed following injury to the developing brain, it is possible that MMPs play an important role in HI injury processes in the developing brain. Therefore, this thesis evaluated the hypothesis that MMP-2 and 9 participate in the pathophysiology of HI injury to the developing brain. Since ECM remodelling is a fundamental process during brain development it was important to first characterise the MMP-2 and 9 profiles in the normal developing forebrain. We demonstrated that MMP-2, which mainly was observed in cortical plate neurons, declined with age, thus indicating a potential role in the development and differentiation of the cortical plate. Conversely, MMP-9 was increased with age, particularly during active myelination, indicating that it may contribute in myelination. Secondly, we showed an upregulation of MMP-9 within the ischemic core during the early hours following HI injury, suggesting that MMP-9 may be involved in the development of delayed injury processes following hypoxic ischemia. On the contrary, MMP-2 was strongly upregulated during a later stage following injury surrounding the ischemic core possibly suggesting that it plays a role in wound repair processes. Thirdly, the profiles of tissue (tPA) and urokinase (uPA) plasminogen activators were characterised following HI injury since they are known to be major upstream activators of MMPs. uPA upregulation paralleled that of MMP-2 suggesting a function for uPA in wound repair processes following HI injury to the developing brain through activation of MMP-2. In contrast with uPA, tPA activity remained unaffected following injury at both ages. Finally, MMP-9 activity was inhibited using a very specific MMP-2/9 inhibitor, SB-3CT, to determine if the MMP-9 deficiency protects the developing brain from HI injury. The elevated MMP-9 activity following HI injury was attenuated by the SB-3CT treatment. Although SB-3CT failed to confer any significant neuroprotection, we recommend that further investigations are needed before discounting the role of MMP-9 during HI injury to the developing brain. In conclusion, we suggest that MMP-9 is induced following an insult to the developing brain potentially contributing to the delayed neuronal death whilst MMP-2 is involved in essential developmental, differentiation and wound repair processes.
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Christophidis, Larissa Joy. "The roles of growth hormone and prolactin in the brain during development and recovery from hypoxic-ischemic injury." Thesis, University of Auckland, 2011. http://hdl.handle.net/2292/6781.
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Very preterm birth disrupts development of the brain and enhances its vulnerability to injury, resulting in neurological impairments ranging in severity from cerebral palsy to mild cognitive deficits. Currently there is no treatment available. Unilateral hypoxic-ischemia (HI) in the three day old rat is well established as a model of brain injury in infants born at 22 to 26 gestational weeks. However, it is inherently variable. I show that this injury results in short term neurological deficits which may be capitalised upon for allocation of pups into treatment studies. After it is injured, the brain tries to repair itself using processes that are a recapitulation of those that occur during brain development. Using a model of injury to the immature brain our laboratory has identified roles for the closely related anterior pituitary hormones growth hormone (GH) and prolactin (PRL) in the brain after injury. Though the role of GH in neuroprotection is well demonstrated, little is known of its capacity for neuro-restoration subsequent to injury. I found that GH receptor immunoreactivity is upregulated in the ipsilateral subventricular zone at five days after injury, corresponding both spatially and temporally with injury-induced neurogenesis. Cells immunopositive for the GH receptor included proliferating and neural precursor cells and post-mitotic neuroblasts. Together with the finding from our laboratory that GH stimulates proliferation of embryonic mouse neural stem cells (NSCs), these results indicate a novel role for GH in injury-induced neurogenesis. Whilst PRL is known to exert effects on neural progenitor and glial cells after injury to the central nervous system, its role in development of extra-hypothalamic brain regions has not been examined. Using a novel real time PCR assay I reveal the ontogeny of the long, fully functional PRL receptor isoform in the rat cerebral cortex and find that it parallels that of neurite initiation and outgrowth markers. Indeed, treatment of neurons derived from adult mouse NSCs with PRL increased the number of primary and secondary neurites. These results implicate a role for PRL in development of the cerebral cortex.
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Kendall, G. "The role of endotoxin, the TNF family of cytokines and intracellular pH in perinatal hypoxic-ischemic brain injury." Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/19212/.
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To explore the effect of endotoxin as a sensitising agent prior to neonatal hypoxiaischemia differing doses of endotoxin (E. coli lipopolysaccharide, LPS) were given to neonatal mice prior to hypoxia-ischemia, with sensitising effects noted at dosages of 0.3mg/kg of LPS or higher. Varying the time interval between endotoxin administration and hypoxia-ischemia demonstrated that LPS given between 4 and 12 hours before hypoxia-ischemia had a sensitising effect on subsequent hypoxia ischemia. In contrast, LPS given at the time of or 24 hours before hypoxia-ischemia did not. To help understand the mechanism by which this sensitising effect occurs, a dose-response study of LPS alone was undertaken. Here, a dose-dependent activation of microglia was demonstrated throughout the brain, particularly in the thalamus and cortex, by 12 hours following endotoxin administration. There was also evidence of vascular endothelial activation (ICAM1) as early as 4 hours after endotoxin administration. To study the role of the TNF cluster of cytokines (TNF alpha, lymphotoxin alpha and lymphotoxin beta), animals with a deletion of the entire TNF cluster were examined. Deletion of the TNF cluster was shown to abolish both endotoxin-mediated sensitisation of the developing brain to subsequent hypoxia, and to prevent upregulation of macrophage and vascular endothelium by endotoxin alone. This study also examined the effects of hypoxia-ischemia on intracellular pH. Increasing duration of hypoxia-ischemia resulted in a progressive intracellular acidosis within the brain, initially ipsilateral to the carotid ligation, but becoming bilateral with prolonged hypoxia. In the reoxygenation phase, there was a rebound intracellular alkalosis at 6 hours of reoxygenation across the whole forebrain. Previous studies have suggested that this alkalosis is mediated by a Na+/H+ exchanger. Blockade of this transporter with N-methyl isobutyl amiloride prior to hypoxia-ischemia was shown to confer neuroprotection in the developing brain.
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Gregg, Robert. "Functional outcomes of hypoxic brain injury : a systematic review : the influence of childhood trauma and coping on the psychosis phenotype in the general population." Thesis, Queen's University Belfast, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.695346.
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Our understanding of psychotic symptoms can be improved by research exploring schizotypal traits in the general population. Investigating the trauma associated with adverse childhood experiences (ACE), and how these may influence coping resources (locus of control and self-esteem) and maladaptive coping is of interest as previous research indicates these variables may contribute to exacerbation of psychotic-like symptoms in clinical and non-clinical populations. This study used questionnaires posted as a survey on Amazon's Mechanical Turk website to gather information on the foregoing variables from 254 participants. Mediation analyses indicated that an external locus of control mediated the association between ACE and maladaptive coping; that maladaptive coping mediated the relationship between an external locus of control and schizotypal traits; and that maladaptive coping fully mediated the relationship between ACE and schizotypal traits. ACE was not associated with low self-esteem, though maladaptive coping mediated the relationship between low self-esteem and schizotypal traits. The results improve our understanding of the nature of the psychosis spectrum. Implications for future research are discussed.
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Xu, Kui. "The Central Nervous System Aspects of Cardiac Arrest and Resuscitation in a Rat Model of Global Ischemia." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1270689501.
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Battin, Malcolm Richard. "Selective cerebral hypothermia for term infants following hypoxic ischaemic injury." 2008. http://hdl.handle.net/2292/5545.
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Perinatal hypoxic ischaemic injury is an important cause of both neonatal death and long-term disability. The sequence of resuscitation followed by a latent phase then a secondary cascade of injury is well documented. This thesis covers key steps toward the utilization of selective hypothermia as an intervention during the latent phase to ameliorate the secondary injury and improve subsequent outcome. The technique was shown to be both feasible and well tolerated. Specifically, a rectal temperature of 35 °C and 34.5 °C, in term infants with neonatal encephalopathy, was not associated with an excessive requirement for cardio-respiratory support. Although a decrease in heart rate occurred during cooling, this was expected and there was no significant change in blood pressure during either the cooling or rewarming phase. Additional reassuring findings were that neither major electrolyte disturbance; hypoglycaemia or haematological changes, including excessive haemorrhage, were observed during hypothermia. The study of neurodevelopmental outcome established that selective cerebral hypothermia was not associated with late adverse effects and, in infants with moderate to severe encephalopathy, the combined cooled groups demonstrated a trend towards better outcome. These data confirmed the potential for selective cerebral hypothermia to provide neuroprotection following perinatal asphyxia. In further chapters cerebral CT scan was confirmed as a helpful adjunct to clinical staging in predicting neurodevelopmental outcome and important clinical experience was reported including rebound seizures following rewarming; sclerema neonatorum associated with hypothermia; and abnormal flow in the superior sagittal sinus, associated with perinatal asphyxia. Lastly a review of infants assessed but not recruited to the CoolCap trial based on aEEG criteria was performed. As these aEEG criteria could be applied to future clinical use it was considered important to ensure large numbers of infants with potential to benefit were not excluded from intervention Neurodevelopmental status for those infants excluded by the aEEG criteria was largely favourable but a small number had adverse outcome and the majority manifested short term morbidity. In conclusion, the work presented in this thesis suggests that intervention with selective hypothermia offers the potential to change disease progression and improve subsequent outcome following perinatal asphyxia at term.Whole document restricted until 11/2014, but available by request, use the feedback form to request access.
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Lai, Pei-Chun, and 賴佩君. "Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rat." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/20603848098666369351.
Full textAbstract:
博士慈濟大學
藥理暨毒理學碩士班/博士班
100
Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE). Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds that enhance the expression of GLT1 may exert neuroprotective effect in HIE. In this study, we used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7) rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Our results showed that pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats. Pre-treatment with 200 mg/kg ceftriaxone improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.
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Sizonenko, Stéphane Vladimir. "Hypoxic-ischemic injury in the developing brain: pathogenesis and neuroprotection." 2002. http://hdl.handle.net/2292/3212.
Full textAbstract:
In newborn infants, birth asphyxia represents the predominant cause of brain injury. These infants will later exhibit neurodevelopmental disabilities or a more major cerebral palsy. Prevention of adverse outcomes requires an understanding of the way in which these deficits develop. Endogenous protective mechanisms arising from the insult have opened new insights in neuroprotective strategies. Neurotrophic factors such as IGF-1 and its N-terminal tripeptide GPE have been shown to confer some neuroprotection after HI injury in the adult rodent. In the P21 rat brain after moderate HI injury, exogenous intracerebral and intraperitoneal injections of GPE (30μg and 300μg respectively) were neuroprotective in the hippocampus and lateral cortex possibly through binding to glia as detected by autoradiography of 3H-GPE. In the preterm infant the mechanisms of white matter injury remain to be clearly elucidated. To mimic the pattern of diffuse cerebral injury of the very preterm infant, a transient moderate focal HI injury has been applied on the immature P3 rat. This new model showed a significant reduction in the lateral cortical volume with reduction and alteration of the myelination pattern in the cortical white matter (WM) at P21. These cortical alterations result from neuro-axonal damage 24h after the insult as shown with Fluoro-Jade B staining and β-APP accumulation. In addition activated astrocytes from 24h after HI up to P21 were present. This model should enable us to elucidate some of the pathogenic mechanisms involved in diffuse WM injury. Brain damage in the developing brain has two components: 1) the pattern and mechanisms of injury are correlated with the stage of development at the time of injury; 2) it will influence subsequent brain development.
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Chang, Kang-Fan, and 張綱凡. "LPS preconditioning mediates neuroprotection against hypoxic-ischemic injury in the neonatal rat brain." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/91278671965730347711.
Full textAbstract:
碩士國立成功大學
微生物及免疫學研究所
92
Perinatal hypoxic-ischemic (HI) brain injury is a major cause of neonatal mortality and long-term disability such as mental retardation, cerebral palsy, learning disability, and seizures. There are still no effective therapies against neonatal HI brain injury to date. A sublethal stress before a lethal injury can reduce the neuronal death, a phenomenon called “preconditioning”. Elucidating the underlying mechanisms of preconditioning may provide potential neuroprotective therapy for neonatal HI encephalopathy. We first established a lipopolysaccharide (LPS) preconditioning model in neonatal rats by pretreating rat pups with a low dose of LPS 24 hours before HI injury on postnatal day 7. We found that the degree of brain injury of LPS-preconditioned rats were significantly less than that of NS-pretreated rats. The behavioral performance measured by Morris water maze of LPS-preconditioned rats was also significantly better than that of NS-pretreated rats. The expression levels of apoptosis markers, such as cleavaged form of caspase-3, caspase-9, poly (ADP-ribose) polymerase (PARP), and the production of reactive oxygen species (ROS) in the cortex were significantly lower in the LPS-preconditioned rats compared to NS-pretreated rats at 24 hours after HI injury. Among the mitogen-activated protein kinases (MAPK) family, LPS preconditioning could increase the phosphorylation levels of extracellular signal-related kinase (ERK) instead of p38. However, inhibition of MAP kinase kinase (MEK) or p38 did not affect the neuroprotection induced by LPS preconditioning. We also observed that LPS could up-regulate ROS production up to 24 hours after LPS injection. However, ROS scavenger, N-(2-mercaptopropionyl) glycine (N-2-MPG), could not abolish the LPS induced neuroprotection. In contrast, toll-like receptor 4 (TLR4) was involved in the LPS-induced neuroprotection since LPS preconditioning could not be induced in the C3H/HeJ mice, a TLR4 deficient mice. In conclusion, we established a LPS preconditioning model in immature rat brains, and the neuroprotection mechanisms in this model involved the down-regulation of ROS production and the reduction of apoptosis. The LPS-preconditioning mechanisms in the neonatal rat brain remain to be elucidated.
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Yi-ChingHsu and 許宜菁. "The mechanism of neurovascular damage in neonatal rat with hypoxic-ischemic brain injury." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/89meyn.
Full textAbstract:
博士國立成功大學
基礎醫學研究所
102
Brain cells are extremely sensitive to oxygen deprivation. Some brain cells actually start dying just under five minutes after their oxygen supply is cut. As a result, brain hypoxia can kill brain cells and rapidly cause severe brain damage. This is an emergency, and the sooner medical attention is given and the oxygen supply restored, the lower the chances of severe brain damage or death. Neonatal hypoxic-ischemic (HI) stress can lead to HI encephalopathy. There is still no effective drug against neonatal HI brain injury. Most neuroprotective agents have not benefitted patients with stroke. Because researchers have reported that neurovascular units can be the targets of hypoxic stress and that both neurons and microvessels respond equally rapidly to the insult, it has been hypothesized that vascular protection would be more effective than neuroprotection against HI brain damage. To clarify the function of neurovascular unit in neonatal HI brain injury, a major cause of neonatal mortality and long-term disability, we used 7-day-old rat pups with an animal model of HI injury: one side carotid artery was permanently ligated and each rat pup was subjected to systemic hypoxia (8% O for 2 h) to induce ipsilateral cerebral HI injury. This study investigated whether neurovascular unit damage is an early event in HI neonatal brain damage and how nitric oxide contributes to HI-induced brain injury. The data show that IgG leakage and microvascular change were observed with transmission electron microscopy (TEM) as early as 1 h after HI insult. Nitrotyrosine was overexpressed immediately after reoxygenation. The hypothesis that “microvascular damage occurs soon after hypoxic-ischemia: neuronal nitric oxide synthase (nNOS) is activated and contributes to brain injury” was tested. Treating the rat pups with 7-nitroindazole (7-NI), an nNOS inhibitor, and aminoguanidine (AG), an inducible NOS (iNOS) inhibitor, before hypoxia provided complete and partial neuroprotection, respectively. I also use ischemic preconditioning (IP) as a complete brain protection model for comparison. Pretreatment with 7-NI and IP protected cerebral blood flow (CBF) from hypoxia-induced hypoperfusion that reduced the brain infarct area. In summary, nNOS-mediated vascular damage is an early event caused by hypoxic-ischemia and that vascular protection might be better than neuroprotection. However, how the IP is related to endothelial cells requires additional investigation.
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Wu, Hsin-Chieh, and 吳欣潔. "The Effect of Neonatal Obesity on Hypoxic-ischemic Brain Injury in Rat Pups." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/70012301530373508973.
Full textAbstract:
碩士國立成功大學
分子醫學研究所
95
Perinatal hypoxic–ischemic (HI) brain damage remains a major cause of acute mortality and chronic neurologic morbidity in children. Obesity is a growing problem in modern society. Evidence has shown that obese adult persons suffer a higher risk of stroke and have worse prognosis than non-obese adults. Here, using a well-established HI brain injury model in neonatal rats, we first tested the hypothesis that the over-fed (OF) obese rat pups had a higher degree of HI brain injury compared with the normal-fed (NF) rat pups. The OF group, defined by reducing the litter size to 6 pups from postnatal day 1 (P1), had a significantly higher body-weight (P<0.001), excess fat deposition in the subcutaneous and perirenal space (P<0.001) and bore hyperglycemia (P<0.01) at P7 compared with the NF group defined by keeping the litter size of 12 pups. The OF-HI group had a higher mortality rate than the NF-HI group during HI. In addition, the OF-HI survivors showed a significantly poorer learning behavior performance assessed by water maze task and higher degree of brain damage measured by pathology at adulthood. Twenty-four hours after HI, more brain damage (Nissl stain) and more TUNEL postive cells were observed in the OF-HI brain than in the NF-HI brain. Caspase-3 activation also significantly increased in cerebral cortex in the OF-HI group compared with the NF-HI group. Immunofluorescence imaging showed that the OF-HI group had increased number of injured cells that exhibited pyknotic morphology and cells that showed nuclear translocalization of apoptotic inducing factor in the cortex and hippocampus than the NF-HI group. These results suggest that mitochondria-dependent apoptosis is involved in the obesity-aggravated HI neuronal death in the neonatal rat brain. Thus, we examined whether the over-nutrient status in the neonatal period would cause endoplasmic reticulum (ER) stress and hyperactivation of c-Jun N-terminal kinase (JNK). Our results showed that there was no difference in the ER chaperon protein Grp78 expression between the two groups. In contrast, the OF pups had higher levels of activated JNKs in the cortex than the NF group before and after HI. Furthermore, the OF-HI group had increased phosphorylation at Ser65 site of cell death molecular BIMEL, and the activation of stress-activated protein kinase p38 was not detected after HI in the two groups. Intracerebroventricular administration of JNK inhibitor SP600125 was operated to prove the causal relationship of JNK hyper-activation in neonatal obesity-aggravated HI brain injury. In the OF-HI group, JNK inhibition reduced the mortality during HI and BIMEL phosphorylation after HI, and also provided significant neuroprotection at pathological level. In conclusion, our study shows that obesity in the neonatal period could aggravate HI neuronal death and JNK activation plays a significant role in obesity-aggravated HI neuronal death in neonatal rats.
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Scheepens, Arjan. "Studies on the GH/IGF axis in the infant rat brain following hypoxic ischemic injury." 1999. http://hdl.handle.net/2292/3200.
Full textAbstract:
Brain injuries, be they hypoxic, ischemic, traumatic or neurodegenerative result in permanent neurological deficit and presently there are few or no therapeutic interventions available. Recent research into how and why brain cells die after an insult has elucidated that a significant number of cells die in an apoptotic manner. Following a transient brain injury cells continue to die for upto 5 days after the insult thereby giving a window of opportunity for treatment. In response to injury, the brain produces a range of neurotrophic hormones including insulin-like growth factor 1 (IGF-I), which are thought to act as endogenous neuroprotective agents. This response occurs earlier and to a greater extent in the young. Studies have shown that the exogenous administration of these neurotrophic hormones after brain injury can prevent some cell death, likely through an inhibition of apoptosis. In these studies a well characterised model of HI brain injury in the juvenile rat was used to investigate the response of the IGF-I and growth hormone (GH) axes to brain injury. The action and transport of IGF-I is partly regulated by six binding proteins (IGFBP1-6) for which the response of IGFBP 1-5 to neural injury has been shown. The starting point therefore is a description of the response of IGFBP-6 to HI brain injury. Although the GH receptor is widely expressed in the brain on both neurones and glia, no reports have definitively shown the existence of its ligand, GH within the brain. Here I show that the GH receptor is differentially regulated after neural injury and that its immunolocalisation suggests an importation mechanisms for peripheral GH into the injured CNS, via the choroid plexus. Furthermore I show that a GH-like substance is strongly upregulated after injury, specifically associated with stressed and dying neurones and glia. Subsequently, I show that intracerebral infusions of rat GH into the injured rat brain conveys significant protection exclusively to GH receptor bearing neurones. In summary, these data show a GH-like substance may be acting as a new neurotrophic factor which is upregulated after brain injury and may act as an endogenous neuroprotective agent.
30
Ming-CheLee and 李明哲. "Inhibition of HDAC activity by sodium butyrate attenuates hypoxic-ischemic injury in the neonatal brain." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/95704696191172209196.
Full textAbstract:
碩士國立成功大學
分子醫學研究所
98
Background: Hypoxic-ischemia (HI) encephalopathy is a major cause of neonatal mortality and subsequent neurodevelopmental disability in the surviving infants, however, there is still no effective treatment. Recent studies have showed that increased histone acetylation by inhibitors of histone deacetylase (HDAC) protects against neurodegenerative disorders and acute cerebral ischemia in adult animals. The neuroprotective effect of HDAC inhibitors involves transcription activation through increasing histone acetylation of prosurvival genes. Hypothesis: This study was to test the hypotheses that increased histone acetylation by a HDAC inhibitor- sodium butyrate (SB): 1) provides neuroprotection against HI, and 2) increases neuroplasticity after HI in the neonatal rat brain through chromatin remodeling and upregulating protective factors. Materials and methods: In the pre-treatment part, we intraperitoneally injected SB (1.2 and 1.8 g/kg) or vehicle (normal saline) daily in SD rat pups from postnatal (P) day 1 to P7. On P7, rats were subjected to HI induced by permanent ligation of unilateral carotid artery followed by 2 hours of 8% O2 hypoxia at 37°C. Histone acetylation, apoptosis and inflammatory marker activity were investigated by western blotting before and after HI. Behavior test was performed by Morris water maze ,and inhibitory avoidance test from P42 to P49, and brain injury was investigated by pathology on P49. In the post-treatment part, we treated the pups with SB or vehicle daily after HI from P14 to P42. Behavior test measured by Morris water maze test and inhibitory avoidance test was done from P42 to P49 and brain injury by pathology on P49. Results: In the pretreatment part, compared with vehicle, SB pretreatment (1.8g/kg) significantly reduced HI injury in the cortex (P＜0.001), striatum (P＜0.05) and hippocampus (P＜0.01) and improved learning and memory performance (P ＜0.05). SB pretreatment (1.2g/kg) didn’t show protective effect in pathology and learning and memory performance, compared with vehicle group. Western blotting analysis showed that SB (1.8g/kg) increased acetylation levels of histone H3 and H4, and down-regulated apoptotic (caspase-3, PARP) and inflammatory (COX-2, p53) markers after HI. SB also increased Bcl-xL mRNA expression (3.2 fold) and heat shock protein 70 (HSP70) mRNA and protein levels. We also found that SB upregulated acetylation levels of Sp1, a transcription factor of HSP70. In the post-HI treatment part, SB post-treatment did not provide protective effect at pathology and behavioral levels. Conclusion: SB treatment before HI provides neuroprotection in the neonatal rat brain in association with down-regulating apoptotic and inflammatory responses and up-regulating HSP70 possibly through Sp1 acetylation. In contrast, SB post-treatment after HI does not upregulate neuroplasticity.
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Lee, Hsueh-Te, and 李學德. "The neuroprotective mechanisms of carotid artery ligation-induced preconditioning against neonatal hypoxic-ischemia brain injury." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/72625919712700630778.
Full textAbstract:
博士國立成功大學
基礎醫學研究所
94
Perinatal hypoxic-ischemic brain injury is a major cause of permanent neurological dysfunction in children. An approach to study the treatment of neonatal hypoxic-ischemic encephalopathy that allows for neuroprotection is to investigate the states of tolerance to hypoxic-ischemia. Twenty-four-hour carotid-artery-ligation preconditioning established by delaying the onset of hypoxia for 24 h after permanent unilateral carotid ligation in neonatal rats markedly diminished the cerebral injury. Although much has been learned about the ischemic preconditioning mechanisms in adult rats, the signaling mechanisms of this 24-h-carotid-artery-ligation preconditioning in neonatal rats remain unknown. We demonstrated that carotid artery ligation 24 h before hypoxia on postnatal day 7 (P7) rat pups provided complete neuroprotection, while artery ligation 6 h produced intermediate benefit, at behavioral and pathological levels compared to ligation 1 h before hypoxia. We first showed that the 24-h-carotid-artery-ligation preconditioning was associated with a robust and sustained activation of cAMP response element-binding protein (CREB), a transcription factor that acts as a key mediator of stimulus-induced nuclear responses underlying learning and memory, survival, and synaptic plasticity of the nervous system. Intracerebroventricular infusions of antisense CREB oligodeoxynucleotides significantly reduced the 24-h-carotid-artery ligation-induced neuroprotection by decreasing CREB expression. Pharmacological activation of the cAMP-CREB signaling with rolipram 24 h prehypoxia protected rat pups at behavioral and pathological levels by sustained increased CREB phosphorylation. These findings suggest that CREB activation provides important mechanism for potential pharmacological treatment against neonatal hypoxic-ischemic brain injury. The upstream signaling mechanisms leading to CREB activation, however, in this 24 h carotid-artery ligation preconditioning of neonatal rat brain remained unknown. We next found that vascular endothelial growth factor (VEGF)-A and VEGF receptor-2 (VEGFR-2) instead of VEGFR-1 were expressed in vessels and neurons of the P7 rat brain. Increased angiogenesis and upregulated expression of VEGF-A and VEGFR-2, but not VEGFR-1, was also found in vessels and neurons in the ipsilateral cerebral cortex 24 h after carotid artery ligation. A blockade of VEGF-A or VEGFR-2, instead of VEGFR-1, by antisense oligodeoxynucleotides decreased VEGFR-2 and pCREB expression and abolished the neuroprotective effect of carotid artery ligation preconditioning. In contrast, VEGF-A treatment or selective activation of VEGFR-2 before hypoxic-ischemia selectively upregulated VEGFR-2 and pCREB expression and provided neuroprotection against neonatal hypoxic-ischemic brain injury. Furthermore, selective activation of VEGFR-2 but not VEGFR-1 after hypoxic-ischemia also significantly protected P7 rat pups against hypoxic-ischemic brain injury. Further in vitro oxygen-glucose deprivation (OGD) study confirmed that VEGFR-2 and CREB activation was required for VEGF-A-induced neuroprotection against oxygen glucose deprivation neuronal death in differentiated H19-7 cells. Taken together, these in vivo and in vitro evidences suggest that VEGF-A/VEGFR-2 signaling leading to CREB activation is an important event in neuroprotection against hypoxic-ischemic injury in the neonatal brain. Pharmacological activation of VEGFR-2 might be an important strategy for the treatment of neonatal hypoxic-ischemic brain injury.
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Ming-YiHuang and 黃名儀. "Endothelial IRS-1 aggravates neurovascular damage after neonatal hypoxic-ischemic brain injury through increasing neuroinflammation." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/nppwu2.
Full textAbstract:
碩士國立成功大學
臨床醫學研究所
103
Perinatal hypoxic-ischemia (HI) is a major cause of neonatal mortality and long-term neurological morbidity among survivors. HI injury not only causes neuron death but also damages endothelial cells within neurovascular unit. Maintaining the integrity of whole neurovascular unit is required for proper brain function. Disruption of neurovascular unit, especially cerebral microvascular endothelial cells, leads to BBB perturbation and causes vasogenic cerebral edema and secondary neuronal damage, which eventually exacerbates long-term disability. Thus, there is a new idea to develop means to protect the vasculature to improve HI outcome. Our previous study found that dietary restriction (DR) reduced neurovascular damage after HI and conferred long-term protection in the neonatal brain through insulin receptor substrate-1 (IRS-1)-Akt pathway. Moreover, IRS-1 over-expression protected against oxygen-glucose deprivation (OGD) cell death mainly in the endothelial cells. Therefore, an endothelium specific IRS-1 transgenic rat was created to delineate the role of IRS-1 in vascular endothelial cells against HI in the neonatal brain. We found that over-expressed IRS-1 in the vascular endothelial cells worsened the HI infarct volume with decreased tight junction proteins expression, and increased matrix metalloprotein 9 (MMP 9) production and BBB damage. Since upregulating adhesion molecules of endothelium increases peripheral leukocytes infiltration in to the damaged brain tissue and subsequently worsen the brain injury, we further investigated the expression of adhesion molecules, such as intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in our transgenic rats. We found endothelial IRS-1 transgenic pups had upregulated VCAM-1 expression as early as 3 hours and ICAM-1 expression at 24 hours after HI. It associated with significantly increased microglia activation and neutrophils infiltration at 24 hours after HI. The in vitro experiments confirmed that IRS-1 over-expression in human brain microvascular endothelial cells could increase VCAM-1 and ICAM-1 expression before and after oxygen-glucose deprivation (OGD). Blockage of VCAM-1 and ICAM-1 using anti-VCAM-1 and anti-ICAM-1 antibody in our transgenic rats decreased neuronal apoptosis, and attenuated MMP 9 production, microglia activation and neutrophils infiltration after HI. In conclusion, IRS-1 specific over-expression in the vascular endothelial cells enhanced VCAM-1 and ICMA-1 expression, and exaggerated neuroinflammation and neurovascular damage after HI in the neonatal brain.
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Lin, Wan-Ying, and 林宛瑩. "Anti-apoptotic mechanism of ischemic preconditioning against hypoxic-ischemic injury in the neonatal rat brain." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/7j466r.
Full textAbstract:
碩士國立成功大學
分子醫學研究所
93
Neonatal hypoxic-ischemic (HI) brain injury is a major cause of neonatal mortality and long-term disability. Currently, there are still no effective therapies against neonatal HI brain injury. A sublethal stress, such as a brief episode of ischemia, before a lethal injury may reduce neuronal death against subsequent lethal injury; a phenomenon called “preconditioning”. Elucidating the underlying mechanisms of preconditioning may provide potential neuroprotective therapy for neonatal HI brain injury. Permanent ligation of unilateral carotid artery followed by systemic hypoxia (8% O2 for 2 h) could induce ipsilateral cerebral HI injury in 7-day-old rat pups. To test whether the ischemia preconditioning (IP) could be established in neonatal brain in a time-dependent manner, rat pups were subjected to HI at 22 h (IP-22h group), 6 h (IP-6h group) or 2 h (IP-2h group) after reversible unilateral carotid artery ligation for 2 h. The outcome was measured by behavior assessment (P35) and pathology (P40) (percentage of brain weight reduction) and behavior (Morris water maze) on P35-P40. Compared to the No-IP group, all the three IP groups had significantly neuroprotective effect at morphological and behavioral levels. Among the three IP groups, the IP-6h group had the worst behavioral performance and also showed more TUNEL positive cells in the cortex and hippocampus. Twenty-four hours after HI, the reactive oxygen species (ROS) production and the expression levels of the cleavaged form of pro-apoptotic markers, such as caspase-3, caspase-8, caspase-9, poly (ADP-ribose) polymerase, and apoptosis inducing factor, were significantly lower in the IP-22h group compared to the no-IP group. In addition, the release of cytochrome c and Smac from mitochondria to cytosol after HI was also significantly reduced in the IP-22h group. In contrast, the expression of anti-apoptotic markers, such as cellular inhibitor of apoptosis-1(cIAP-1) and BCL2, but not X-linked inhibitor of apoptosis, were significantly higher in the IP-22h group. Increased expression of cIAP-1 but not activated caspase-3 was also found in the IP-22h group during preconditioning phase. Our study suggests that but both rapid and delayed phase of IP can be established in the immature brain, suggesting the unique plasticity in the development brain. In addition, IP-mediated neuroprotective mechanisms in the immature brain involve not only the inhibition of apoptosis (caspase-dependent and caspase-independent pathways, and intrinsic and extrinsic pathways) but also increase expression of anti-apoptotic markers, such as cIAP-1. Further work will be extended to determine the role of cIAP-1 in IP and elucidate its upstream signaling during IP in the immature rat brain.
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Chien-HangTseng and 曾千航. "Lipopolysaccharide Sensitizes Hypoxic-ischemia Injury in the Immature Brain through Tumor Necrosis Factor Receptor 1 Signaling." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/85537877104177878639.
Full text
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Hsiang-YinLin and 林相吟. "The protective mechanism of low-dose lipopolysaccharide preconditioning against hypoxic-iscjemic brain injury in neonatal rats." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/21367016492112758777.
Full textAbstract:
博士國立成功大學
基礎醫學研究所
98
Hypoxic-ischemic encephalopathy (HIE) in newborn is a common and important neonatal disease. It always resulted in learning disability, mental retardation, cerebral palsy and even fetal death and there is no effective prevention or therapy for HIE. Based on the concept of preconditioning, which is a sub-lethal insult providing tissue or organs resistance to subsequent lethal insult, we established a low-dose lipopolysaccharide (LPS, 0.05mg/Kg) preconditioning against hypoxic-ischemic (HI) brain damage on both behavioral (learning and memory ability) and pathological levels (Brain weight reduction) in the neonatal rats. Delineating the underlying protective mechanisms of LPS preconditioning is the aim of this study. We found that LPS preconditioning-derived eNOS up-regulation and PI3K/Akt activation in cortical neuron and cerebral vessels are required for the neuroprotection. And the PI3k/Akt activation is responsible for the eNOS up-regulation. In vitro study showed that the expression level of eNOS is associated with the susceptibility to HI in neuronal cell and vascular endothelial cell. Low-dose LPS preconditioning-mediated PI3K/Akt-eNOS is suggested to contribute to neuro-vascular protection in the immature brain. It implicated that eNOS up-regulation is a potential approach for clinical prevention of HIE. We also got insight into how low-dose LPS preconditioning influences the pathogenetic cascades of HI brain injury including ROS accumulation, neuroinflammation, apoptotic cell death and apoptotic signaling cascades. Our findings revealed that low-dose LPS preconditioning reduced HI-induced inflammation, apoptosis and oxidative stress in the neonatal HI brain. And LPS preconditioning-mediated neuroprotective effects were correlated with LPS preconditioning-mediated GSK-3 beta inhibition after HI. Inhibition of GSK-3 beta by pretreatment of GSK-3 beta inhibitor ( lithium chloride) 30 minutes before HI can mimic LPS preconditioning-induced neuroprotective effects including anti-apoptotic and anti-inflammatory effects in the neonatal HI brain. It implicated that GSK-3 beta activation contributes to the pathogenesis of neonatal HI brain injury and inhibition of GSK-3 beta may be required for the acquisition of LPS preconditioning. Taken all together, we have demonstrated the protective mechanisms underlying low-dose LPS preconditioning against HI brain injury in neonatal rats. And it may be helpful for designing potential clinical therapy or prevention for HIE.
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Yi-LunChiang and 江宜倫. "Shear stress and erythromycin stimulations in endothelial cells for treatment of neonatal hypoxic-ischemia brain injury." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/s85d6f.
Full textAbstract:
碩士國立成功大學
細胞生物與解剖學研究所
105
Stem cells can differentiate to endothelial lineage as a source for tissue engineering of vessels. However, the rarity of cell source and low differentiation efficiency are the main limitation for stem cell therapy in vessel regeneration. Our previously study demonstrated a successful endothelial cell (EC) differentiation by integration of biomechanical force and chemical factors, but the mechanism is still unknown. Furthermore, we build up a cell therapy of brain hypoxic-ischemia (HI) model by using human umbilical vein endothelial cells (HUVECs). The differentiated cells will apply to this animal model in the future. By static HUVECs transplantation in brain HI model, brain injury and cell death were decreased. Laminar shear stress (LSS)-treated HUVECs group in animal model had not significantly repair function than static HUVECs. Previously research indicates that CXCR4, a chemoattractant receptor, is reduced by LSS. One paper showed that erythromycin (EM) increased CXCR4 expression. Therefore, we combined LSS with EM to stimulate HUVECs. We found that EM treatment after LSS stimulation of HUVEC transplantation was useful for rescuing brain injury. In this study, we built up successful cell therapy for brain injury model. Furthermore, repair function of ECs can be enlarged by increasing EM-induced CXCR4 expression.
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Dunlop, Kate. "Neuroprotective Effects of a Novel Apple Peel Extract AF4 in a Mouse Model of Hypoxic-Ischemic Brain Injury." 2011. http://hdl.handle.net/10222/13997.
Full textAbstract:
The neuroprotective effects of AF4, a flavonoid-enriched extract derived from the
peel of Northern Spy apples (containing quercetin-3-O-glucoside, quercetin-3-O-galactoside,
quercetin-3-O-rhamnoside, quercetin-3-O-rutinoside, epicatechin, and
cyanidin-3-O-galactoside) were examined by assessing neuronal loss and motor
impairment resulting from hypoxic-ischemic (HI) brain injury in adult C57BL/6 mice.
Relative to vehicle treatment (water, 10mL/kg/day), oral administration of AF4 (50
mg/kg/day) for 3 days reduces HI-induced neuronal loss in the striatum and
hippocampus, motor impairments, and reduces the ability of LPS to stimulate the
production of TNF-alpha in whole blood. Pretreatment with AF4 (1 ug/mL) decreased the
death of mouse primary cortical neurons subjected to oxygen glucose deprivation (12
hours) in comparison to vehicle (DMSO) or the same concentration of quercetin or its
metabolites. Taken together these findings indicate that AF4 reduces HI-induced brain
injury and motor deficits by increasing the resistance of vulnerable neurons to ischemic
cell death and decreasing the production of inflammatory cytokines.
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Dunlop, Kate Elizabeth. "Neuroprotective Effects of a Novel Apple Peel Extract AF4 in a Mouse Model of Hypoxic-Ischemic Brain Injury." 2011. http://hdl.handle.net/10222/15722.
Full textAbstract:
The neuroprotective effects of AF4, a flavonoid-enriched extract derived from the
peel of Northern Spy apples (containing quercetin-3-O-glucoside, quercetin-3-O-galactoside,
quercetin-3-O-rhamnoside, quercetin-3-O-rutinoside, epicatechin, and
cyanidin-3-O-galactoside) were examined by assessing neuronal loss and motor
impairment resulting from hypoxic-ischemic (HI) brain injury in adult C57BL/6 mice.
Relative to vehicle treatment (water, 10mL/kg/day), oral administration of AF4 (50
mg/kg/day) for 3 days reduces HI-induced neuronal loss in the striatum and
hippocampus, motor impairments, and reduces the ability of LPS to stimulate the
production of TNF-alpha in whole blood. Pretreatment with AF4 (1 ug/mL) decreased the
death of mouse primary cortical neurons subjected to oxygen glucose deprivation (12
hours) in comparison to vehicle (DMSO) or the same concentration of quercetin or its
metabolites. Taken together these findings indicate that AF4 reduces HI-induced brain
injury and motor deficits by increasing the resistance of vulnerable neurons to ischemic
cell death and decreasing the production of inflammatory cytokines.
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Guan, Jian. "Insulin-like growth factor-1 after hypoxic-ischemic brain injury: effects and modes of action on neuronal survival." 1996. http://hdl.handle.net/2292/3116.
Full textAbstract:
Insulin/insulin-like growth factor (IGF)s naturally occur in the central nervous system (CNS) and have an important role in cell proliferation and differentiation during brain development and maturation. IGFs, IGF binding protein (IGFBP)s and their receptors are expressed in damaged brain regions suggesting a role for the IGFs system after brain injury. It is now known that neurons can die some hours, even days after an injury. This programmed death is termed delayed neuronal death (DND). The process of DND might provide a therapeutic window of opportunity for insulin/IGFs to reduce brain damage after an insult. Unilateral hypoxic-ischemic (HI) brain injury was induced using a modified Levine rat model. Intracerebral ventricular (ICV) administration was chosen for the delivery of the peptides. The effects of IGF-1 on neuroprotection were tested when given either before or after the HI insult. The dose response of IGF-1 on neuronal rescue was also determined. The distribution of IGF-1 after HI injury was examined following central administration of 3H-IGF-1. The mode of action of IGF-1 on brain rescue was studied by comparing the treatment effects of IGF-1, IGF-2, des-N-(1-3)IGF-1 (des-IGF-1), insulin, N-terminal tripeptide of IGF-1 (GPE) and (+)-5-Methy1-10,11-dihydro-1H-dibenzo[a,d]cyclo-hepten-5,10-iminemaleare (MK801). IGF-1 reduced cortical infarction and neuronal loss when given after, but not before, an HI insult in a dose dependent manner. HI brain injury enhanced the penetration of IGF-1 into the brain parenchyma after ICV administration possibly via perivascular pathways and white matter tracks. The effective dose of IGF-I did not alter cortical temperature and serum glucose concentration. Insulin did not alter the outcome at an equimolar dose to IGF-1. The treatment effect of des-IGF-1 was only found at a higher dose. IGF-2 counteracted the treatment effects of IGF-1 on neuronal rescue and tissue uptake of 3H-IGF-1. An equimolar dose of GPE showed a similar response to IGF-1. MK801, an N-methy1-D-aspartate (NMDA) receptor antagonist did not show significant effect in this model. In summary, IGF-1 was neuroprotective after HI brain injury. The effect of IGF-1 on neuronal rescue depends on the dose and time of delivery. The treatment effect of IGF-1 was independent of hypoglycaemia and hypothermia. The results suggest that this effect is mediated via type one IGF receptors. Distinctive treatment effects by des-IGF-1 and IGF-2 suggested a critical role for IGFBPs on neuronal rescue with IGF-1. A secondary mode of IGF-I action on brain rescue could be through the proteolytic production of GPE. In summary, IGF-1 can improve neuronal outcome in vivo suggesting possible clinic application as a therapeutic agent.
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Sukha, Neelam. "The developmental motor outcomes of infants with hypoxic ischaemic encephalopathy II and III between the ages of 12-14 months at Chris Hani Baragwanath academic hospital." Thesis, 2013.
Find full textAbstract:
A research report submitted to the Faculty of Health Sciences, University
of the Witwatersrand, Johannesburg, in partial fulfilment of the
requirements for the degree of Master of Science in Occupational
Therapy.
Johannesburg, 2013This study determined outcomes for motor developmental delay in infants, 12-14 months, diagnosed with HIE II and III, at Chris Hani Baragwanath Academic Hospital. Twenty nine infants diagnosed with HIE II and nine infants diagnosed with HIE III were assessed using the Peabody Development Motor Scale- 2, at their corrected age. Demographic, antenatal and perinatal factors similar to those in other studies were found for this sample. Infants with HIE III had significantly more developmental delay (p=0.01) than infants with HIE II. Fifty two percent of infants with HIE II had no delay while a 100% of infants with HIE III presented with disability. A greater percentage of infants had delay in fine motor skills. Infants with severe and moderate disabilities were receiving intervention whereas those mild disabilities were often missed in screening clinics. It is vital to ensure these infants are assessed and followed up to remediate difficulties as soon as they arise.
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FitriHandayani and 蘇涵亭. "Protection of neurovascular structure from hypoxic-ischemic brain injury by different progenitor cells derived from adipose-derived stem cell." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/ykhwz8.
Full textAbstract:
碩士國立成功大學
細胞生物與解剖學研究所
102
Adipose-derived stem cells (ASCs) show promise for regenerative medicine researches and able to differentiate into either endothelial or neuronal lineages. The current study aimed to investigate the therapeutic potential of human adipose-derived stem cell for hypoxic-ischemic (HI) brain injury. The HI brain injury was created by right common carotid artery ligation and then exposure to hypoxia (8% O2) for 2h. The human ASCs were differentiated into NPCs and EPCs by culturing ASCs in the chitosan and shear stress microenvironments. The rat pups were divided into 5 groups to receive different treatments by using intra-peritoneum injection, including Naïve, PBS, hASCs, EPCs, NPCs, and combination of EPCs and NPCs (E+N). All rat pups were sacrificed at 7th day after HI. The infracted area and ratio of cell apoptosis were determined by TTC, and Nissl staining. Our results showed significant reduction of cerebral infarction, increase of neurons, and decrease of cell apoptosis after injected with therapeutic cells. Therapeutic effects were analyzed with immunofluorescence staining to detect neurons, astrocytes, and endothelial cells. The quantified results showed that GFAP positive cells on the ischemic side of cortex were lower in therapeutic cell treatment as compared with PBS group. The branch point of vessel and NeuN positive were enhanced after cell therapies for 7 days in HI brain injury. The positive cells with human chromatin staining confirmed the engraftment of transplanted cells homing to the damaged brain. Combination between EPC and NPC involve signaling in Nrp1 signal in EPCs to promote the angiogenesis. Therefore, the progenitor cells from hASCs may benefit as a treatment of HI brain injury.
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Lan-WanWang and 王藍浣. "The Effects of Hypoxic-Ischemia and Inflammation on White Matter Injury in the Immature Brain — Clinical and Experimental Approaches." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/98c2d2.
Full textAbstract:
博士國立成功大學
臨床醫學研究所
101
Very low-birth-weight (VLBW, 〈 1500 g) premature infants have high risk of neurodevelopmental impairment, and cerebral palsy (CP) is the major disability in very preterm survivors. Cerebral white matter injury is the principal brain injury leading to CP in VLBW infants. Hypoxic-ischemia (HI) and inflammation/infection are the two major pathogenic factors of white matter injury and CP. From both experimental and clinical approaches, we examined whether HI and inflammation/infection have joint effects on the risk of CP in very preterm infants, and white matter injury in the immature brain. Objective: Clinical Study: To examine the joint effects of HI and infectious events in the perinatal and neonatal periods on CP risk in VLBW preterm infants. Experimental Study: To investigate whether low-dose lipopolysaccharide (LPS) sensitizes HI-induced white matter injury in the immature brain by selectively up-regulating neuroinflammation and blood-brain barrier (BBB) damage in the white matter; and if so, whether c-Jun N-terminal kinases (JNK) signaling is the shared pathway linking neuroinflammation, BBB leakage and oligodendroglial apoptosis in the white matter injury. Study Design: Clinical Study: From 1995 to 2005, prospective registry of 6318 VLBW preterm infants admitted to Taiwan hospitals was conducted. CP was diagnosed at corrected age 24 months. The cumulative effects of HI and infectious events during the perinatal and neonatal periods on CP risk were analyzed. Experimental Study: Postpartum (P) day 2 rat pups received LPS (0.05 mg/kg) (LPS+HI) or normal saline (NS+HI) followed by 90-minute HI. LPS and NS group were the pups that had LPS or NS only. Immunohistochemistry and immunoblotting were used to determine microglia activation, tumor necrosis factor-alpha (TNF-α), BBB damage, cleaved caspase-3, JNK and phospho-JNK (p-JNK), myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP) expression. Immunofluorescence was performed to determine the cellular distribution of p-JNK. Pharmacological and genetic approaches were used to inhibit JNK activity. Results: Clinical Study: Of the 3946 infants who had completed 24-month neuromotor examinations, 466 (11.8%) had CP, 2238 (56.7%) normal outcomes, and 1242 (31.5%) minor or other impairment. CP group had significantly higher incidences of HI events in the perinatal and neonatal periods, and sepsis in the neonatal period than normal group. Three HI events, including birth cardiopulmonary resuscitation, chronic lung disease and severe apnea/bradycardia, were the most significant predictors for CP. Relative to CP risk for infants with neither HI nor sepsis, the CP odds increased 1.91-fold, 2.22-fold and 5.07-fold for infants with birth cardiopulmonary resuscitation, chronic lung disease, and severe apnea/bradycardia, respectively; while the combination with sepsis increased the odds by 3.05-fold, 3.10-fold and 7.11-fold, respectively. Using the three HI events plus sepsis, CP rates were 10.3%, 18.5%, 28.0%, 41.3% and 55.6% for infants with none, one, two, three and four events, respectively. Experimental Study: Myelin basic protein immunohistochemistry on P11 showed white matter injury in LPS+HI group, but not in NS+HI, LPS and NS groups. In contrast, no gray matter injury was found in the four groups. In the white matter, increases of activated microglia, TNF-α expression, BBB leakage and cleaved caspase-3-positive oligodendrocyte progenitors were much more prominent in LPS+HI group than in the other three groups 24 hours post-insult. Immunoblotting and immunohistochemical analyses showed early and sustained JNK activation in the white matter at 6 and 24 hours post-insult. Immunofluorescence demonstrated up-regulation of p-JNK in activated microglia, vascular endothelial cells and oligodendrocyte progenitors, and also showed perivascular aggregation of p-JNK-positive cells around the vessels 24 hours post-insult. JNK inhibition by AS601245 or by antisense oligodeoxynucleotides significantly reduced microglial activation, TNF-α immunoreactivity, IgG extravasation, and cleaved caspase 3 in the endothelial cells and oligodendrocyte progenitors, and also attenuated perivascular aggregation of p-JNK-positive cells 24 hours post-insult. The AS601245 or JNK antisense oligodeoxynucleotide group had significantly increased MBP and decreased GFAP expression in the white matter on P11 than the vehicle or scrambled oligodeoxynucleotides group. Conclusions: We concluded that HI and inflammation/infection have joint effects on CP risk in very preterm infants, and on the pathogenesis of white matter injury in the immature brain. Clinically, HI events and sepsis across the perinatal and neonatal periods exert cumulative effects on CP risk in VLBW premature infants. Experimentally, low-dose LPS sensitizes HI-induced white matter injury in the immature brain by selectively up-regulating neuroinflammation and BBB damage in the white matter, and JNK signaling is the shared pathway linking neuroinflammation, BBB leakage and oligodendroglial apoptosis in the white matter injury. The clinical and experimental studies may help reduce significant risk factors and develop effective therapeutic strategies against white matter injury to improve neurodevelopmental outcomes of very preterm infants.
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Lin, Chien-min, and 林乾閔. "The basic and clinical researches of Chinese and Western medicine in the prevention and treatment of severe brain injury with hypoxic change." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/17631660336843753740.
Full text
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Dostálová, Veronika. "Vliv cerebrálního hypoxického poškození na kognitivní funkce a psychosociální faktory." Doctoral thesis, 2019. http://www.nusl.cz/ntk/nusl-405841.
Full textAbstract:
Cognitive and psychosocial sequelae following hypoxic brain injury Abstract in English Hypoxic brain injury leads to neuronal necrosis and to other cerebral changes which may affect psychosocial functioning. Although the pathophysiology of cerebral hypoxia is multifactorial, and it is not possible to reliably describe the unified clinical picture of hypoxia patients, the most commonly described psychosocial consequences of cerebral hypoxia are cognitive impairment, increased anxiety and depressive symptoms. The aim of the present study is to characterize cognitive functioning and psychosocial changes of the patients exposing mild intermittent cerebral hypoxia (=chronic form of hypoxia, model of obstructive sleep apnea diagnosed by neurologist) and patients after severe one-time cerebral hypoxia (=acute form of hypoxia, model of cardiac arrest diagnosed by cardiologist). Regardless of the different etiology of particular hypoxia forms described in the theoretical part of the thesis, both forms may lead to neuronal death. In the experimental part we test a hypothesis comparing healthy individuals to patients with acute or chronic form of hypoxia in cognitive performance or anxiety and depressive symptoms. We document a decreased cognitive performance and higher level of state anxiety in a group of patients...