Thesis (Ph. D.)--University of Adelaide, Dept. of Medicine, 1998? / Copies of author's previously published articles inserted. Includes bibliographical references (leaves I-LXIV).

The present study aimed at investigating the neuropsychological sequelae of transient ischaemic attacks. Transient ischaemic attacks are defined as those neurological disorders in which there is complete resolution of neurological symptoms within twenty·four hours. Transient ischaemic attacks may or may not reveal evidence of brain infarcts on imaging studies. In the present study, the neuropsychological sequelae of transient ischaemic attacks in the carotid circulation were investigated since, within the perspective of cognitive neuropsychology, it was assumed that localized changes in cognitive functions could be demonstrated.Since several psychological, medical and neurological factors are known to influence scores·on neuropsychological tests, regression analyses were performed to determine which factors contributed significantly to the variance of scores on neuropsychological tests in the transient ischaemic attack and control groups. Two transient ischaemic attack groups, each comprising forty left and forty right hemisphere involvement patients, were then compared with each other and with a control group of forty general medical patients. Stenosis of the carotid artery formed a significant predictor of test scores in the combined transient ischaemic attack group. When the groups were·analyzed independently, in the left transient ischaemic attack group stenosis predicted performance on the same tests reaching significance for the combined group, and for the Wisconsin Card Sorting Test (Perseverative Score). In the right transient ischaemic attack group, stenosis significantly predicted performance on Digits Forward, Backward and Total, the PASAT (2.4 seconds) and Trails B. On the other hand, education formed a significant predictor of performance on Digits Forward, Digits Backward and Digits Total and the PASAT (all levels) in the control group. Multivariate comparisons revealed that the left and right transient ischaemic attack groups performed worse than the controls on tests of attention, concentration and conceptual flexibi1ity. The left transient ischaemic attack group performed worse than the right transient ischaemic attack group on all tests of attention and concentration, but there was a significantly better performance of the former group on the Rey Auditory Verbal Learning Test (Trial 1), Block Designs and Verbal Fluency. The findings on the PASAT that left transient ischaemic attack patients performed significantly worse than the right hemisphere group ·were considered to be relatively unreported previously in the literature on transient ischaemic attacks. The findings obtained are discussed from a neurocognitive perspective of neuropsychological functioning in transient ischaemic attacks. / Psychology / Ph. D. (Psychology)

Title: Acute neuroinflammatory reaction after focal cerebral ischemia Aim: The aim of this thesis is to evaluate neuroinflammatory response after focal cerebral cortical ischemia. Also, familiarizing with the method of displaying damage of blood brain barriers, neurons and the possibility of detection of microglia cells as a marker of acute neuroinflammatory processes. Methodology: This is an experimental study. We brought about cortical cerebral ischemia in rats using an application of photosensitive dye "bengal red," and a green laser. Two animals were were given the additional application of "Evans blue" in order to visualize the defects of the blood brain barrier. The animals were returned to their cage for the time needed before they were induced terminal anesthesia. This was followed by the process of brain perfusion, slicing the brain in sections 50 µm thick and then applied these sections onto slides. Sections with applied EB were immediately analyzed under the microscope. Sections to illustrate neuronal death were immunohistochemically stained via the Nissl method. Sections visualizing microglial activity were stained using CD11b antibody. Results: Following the induction of focal ischemia there occured brain tissue damage. In the vicinity of lesion there is degeneration of neurons and...

1 Abstract Title: Consequences of experimentally induced perinatal cerebral ischemic lesion. Aim: This thesis aims to present the issues and analyze current knowledge in the field of perinatal brain damage, particularly perinatal cerebral ischemic lesions as the most common brain infarction in children. Basic characteristics of the disease, syndromology, pathophysiological mechanisms and risk factors are emphasized. Following the theoretical background the thesis analyzes current trends as well as the limitations of the diagnostics and therapy. The aim is to highlight the need for early diagnosis and emphasize the potential of preventive treatment strategies. The practical part follows the theoretical background and expands the topic on the analysis of motor and behavioral consequences of experimentally induced perinatal ischemic stroke. Method: Cerebral focal ischemia was induced experimentally by photothrombotic method to seven days old rats. Rose Bengal intravenously followed by continual illumination of the senzorimotor cortex using a green laser beam for 10 minutes was induced platelet aggregation and subsequent thrombosis. Eight animals at age of two months were evaluated for 7 days via observational cages PhenoTyper. Results: The theoretical part collected and processed theoretical data on the...

Title of work: Angiogenesis in the border zones of cerebral ischemia The aims of work: The aim of this diploma thesis was to determinate the parameter of the angiogenesis after focal brain ischemia induced by photothrombosis in P7 rat pups. This thesis should answer the question, if there is some difference in vascular density according to the distance from the lesion and if there is some diference between the vascular density in normal brain and the brain with the lesion. Materials and Methods: Cerebral ischemia was induced in P7 rat pups with photothombic method. Intravenous administration of bengal rose dye was followed by illumination of beam of green laser over the cortex for 5 minutes at 0,5s on/off cycles. Bengal rose dye is potent photosensitive substance and the ilumination resulted in agregation of trombocytes and thrombosis. Cerebral ischemia evolved due to the thrombosis. After two months, the animals were overdosed with urethane and transcardially perfused. Then thein brain were cryoprotected and then cut into 50µm slices and prepaired for histological staining. The stained slices were the investigated under mikroskope. The microvessels in the cortex were counted and the density was estimated by stereological method. Results: Two brain with ischemic lesion and two control brain were...

The Effect of Sulindac was studied on an animal model of ischemic stroke. Sulindac, a non steroid anti inflammatory drug (NSAID) could protect cell death due to hypoxia/reoxygenation. This drug was given 2 days before and 24 hrs after ischemia until animals were sacrificed on 3rd or 11th day. Infarct size was measured for these animals. Sulindac induced Hsp 27 in ischemic penumbra and core on Day 3 & 11 with uncoated nylon suture which shows its cell-survival and anti-apoptotic activity. Also, it increased expression of cell survival markers such as Akt, Bcl2 & Grp 78 in ischemic penumbra and core. With silicon suture it reduced expression of Hsp 27 in ischemic penumbra and core, alleviating cell stress and having pro-survival and anti-stress effects. In conclusion sulindac may have excellent potential as neuro protective agent against oxidative stress in cerebral ischemia. / by JIgar Modi. / Thesis (M.S.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

Ischemic stroke has a multiplicity of pathophysiological mechanisms. Granulocyte-colony stimulating factor (G-CSF) is an endogenous growth factor that exerts a diverse range of neuroprotection against ischemic stroke. Several lines of evidence demonstrated the contribution of endoplasmic reticulum (ER) in apoptotic cell death involving ischemia. Cell culture of undifferentiated PC12 cells were subjected to 10mM glutamate and selected doses of G-CSF (25ng/ml, 50ng/ml, 100ng/ml and 250ng/ml) for 24 hours. Cell viability, expression of the G-CSF receptor and expression level of CHOP were assessed in vitro. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Rats were subcutaneously injected with G-CSF (n= 15; 50ug/kg body weight) 24 hours post-MCAO for 4 days. Vehicle treated rats were administered 5% dextrose for 1 day (n=4) or 4 days (n=16). Sham-operated rats (n=9) were not subjected to MCAO. Neurological deficit and infarct volume were measured while expression levels of pAKT, Bcl2, Bax, Bak, cleaved caspase-3, GRP78, ATF4, ATF6, p-p38MAPK, pJNK, CHOP and HSP27 were analyzed by western blotting. In vitro G-CSF receptor was expressed on undifferentiated PC12 cell, and an optimal dose of 50 ng/ml G-CSF significantly protected these cells against glutamate-induced cytotoxicity (P < 0.05). G-CSF significantly down-regulated (P < 0.01) the ER stressinduced pro-apoptotic marker CHOP in vitro. In vivo, G-CSF reduced infarct volume to 50% while significantly improved neurological deficit compared to vehicle rats. G-CSF significantly (P < 0.05) up-regulated pro-survival proteins pAKT and Bcl2 while downregulating pro-apoptotic proteins Bax, Bak and cleaved caspase 3 in the ischemic brain. It also significantly (P < 0.05) downregulated the ER intraluminal stress sensor GRP78, proteins of ER stress induced intracellular pathway; ATF4, ATF6, p-p38MAPK, pJNK and the ER stress induced apoptotic marker CHOP, which suggests that ER stress is being ameliorated by G-CSF treatment. G-CSF also reduced the level of HSP27, providing additional evidence of cellular stress reduction. G-CSF treatment increased cell survival by attenuating both general pro-apoptotic proteins and specific effector proteins in the ER stress induced apoptotic pathways. Our data has provided new insight into the anti-apoptotic mechanism of G-CSF, especially as it relates to ER stress induced apoptosis in ischemia. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection

INTRODUÇÃO: A isquemia cerebral é uma doença de alta prevalência, com desfecho clínico imprevisível, e com profilaxia e tratamento ainda limitados. Na atividade neurocirúrgica, as duas situações em que a isquemia cerebral ocorre com maior freqüência são o vasoespasmo arterial, que ocorre após hemorragia subaracnóidea, e nas microneurocirurgias vasculares, especialmente naquelas em que são realizadas clipagens vasculares temporárias. Dentre todas as formas de neuroproteção a hipotermia tem se mostrado a mais promissora em estudos experimentais. Pode ser aplicada em diferentes momentos do processo isquêmico (pré, intra ou pós-isquemia), sendo a modalidade pré-isquêmica pouco explorada na literatura. O objetivo deste estudo foi avaliar comparativamente o efeito da hipotermia pré, intra e pós-isquêmica na isquemia focal temporária por oclusão da artéria cerebral média em ratos, através de análise morfométrica computacional. MATERIAL E MÉTODOS: Foram utilizados 74 ratos machos adultos da linhagem Wistar, divididos em 6 grupos, com 10 animais cada: Controle (C), Sham (S), Controle-Isquêmico (CI), Hipotermia Pré-Isquêmica (IH1), Hipotermia Intra-Isquêmica (IH2), Hipotermia Pós-Isquêmica (IH3). Todos os animais dos grupos isquêmicos foram submetidos à isquemia de 60 minutos, com um período reperfusional de 24 horas. A hipotermia utilizada foi do tipo leve (32 - 34 ºC). No grupo IH1 a hipotermia foi iniciada 30 min antes da oclusão arterial e mantida durante toda a isquemia; no grupo IH2 a hipotermia foi mantida somente durante a isquemia; no grupo IH3 a hipotermia foi mantida por 6 horas, sendo iniciada no exato momento da reperfusão. Após a eutanásia os cérebros foram perfundidos e fixados, sendo realizadas secções coronais de 10 micrômetros, em toda a extensão da área isquêmica, as quais foram coradas pela técnica Luxol Fast Blue. A morfometria foi realizada pelo programa KS400, Carl Zeiss, obtendo-se medidas diretas separadas de cada hemisfério, das áreas em azul (fibras mielinizadas) e em vermelho (corpos neuronais), bem como a área total de cada secção. Medidas derivadas (área isquêmica média, e volumes isquêmicos parcial e aproximado) de cada animal, foram obtidas nos grupos submetidos à isquemia. RESULTADOS: Os parâmetros da homeostase dos animais permaneceram dentro dos limites aceitáveis para este tipo de experimento. Em relação às áreas de fibras mielinizadas (azul) não houve diferença significativa entre os grupos C vs. S (p=0,39, Mann-Whitney-Wilcoxon), CI vs. IH3 (p=0,85, Mann-Whitney-Wilcoxon), e IH1 vs. IH2 (p=0,63, Mann-Whitney-Wilcoxon); ocorreu diferença estatística entre os grupos C vs. CI (p=0,0001, Mann-Whitney-Wilcoxon), CI vs. IH1 (p=0,01, Mann-Whitney-Wilcoxon), e CI vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). Em relação às áreas de corpos neuronais (vermelho), não houve diferença significativa entre os grupos C vs. S (p=0,48, Mann-Whitney-Wilcoxon), CI vs. IH3 (p=0,27, Mann-Whitney-Wilcoxon), e IH1 vs. IH2 (p=0,68, Mann-Whitney-Wilcoxon); ocorreu diferença estatística entre os grupos C vs. CI (p=0,0001, Mann-Whitney-Wilcoxon), CI vs. IH1 (p=0,009, Mann-Whitney-Wilcoxon), e CI vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). A análise estatística das áreas isquêmicas médias, e dos volumes isquêmicos parciais e aproximados não mostrou diferença significante na comparação entre os grupos CI vs. IH3 (p=0,57, Mann-Whitney-Wilcoxon), e IH1 vs. IH2 (p=0,79, Mann-Whitney-Wilcoxon); mostrou diferença significante entre os grupos CI vs. IH1 (p=0,0001, Mann-Whitney-Wilcoxon), e CI vs. IH2 (p=0,0011, Mann-Whitney-Wilcoxon). CONCLUSÕES: As hipotermias pré-isquêmica e intra-isquêmica mostraram-se neuroprotetoras de forma semelhante, o que não ocorreu com a hipotermia pós-isquêmica. / INTRODUCTION: Cerebral ischemia is a high prevalent disease, with unpredictable clinical outcome, and prophylaxis and treatment remains limited. In the neurosurgical practice cerebral ischemia occurs most frequently due arterial vasospasm after subarachnoid hemorrhage, and in vascular microneurosurgery, mainly when temporary vascular clipping is performed. Among all forms of experimental neuroprotection, hypothermia has been the most promising. It can be applied at different moments of ischemia (pre, intra or post-ischemia), and the pre-ischemic modality is little explored in literature. This study aimed to evaluate comparatively the effect of pre, intra and post-ischemic hypothermia in temporary focal ischemia obtained by middle cerebral artery occlusion in rats, by computational morphometric analysis. MATERIAL AND METHODS: We used 74 Wistar adult male rats divided into six groups of 10 animals each: Control (C), Sham (S), Ischemic-Control (IC), Pre-Ischemic Hypothermia (IH1), Intra-Ischemic Hypothermia (IH2), Post-Ischemic Hypothermia (IH3). All animals in the ischemic groups were subjected to ischemia for 60 minutes with a reperfusion period of 24 hours. It was used mild hypothermia (32 - 34 ºC). In IH1 group hypothermia was initiated 30 minutes before arterial occlusion and maintained throughout the ischemia, in IH2 group hypothermia was maintained only during ischemia, IH3 group hypothermia was maintained for 6 hours, starting at the beginning of the reperfusion. After euthanasia, the brains were perfused and fixed, and coronal sections of 10 microns were performed to the fullest extent of ischemic area, and these sections were stained by Luxol Fast Blue. The morphometry was performed by the KS400 software, Carl Zeiss, obtaining direct separated measurements in each hemisphere, of blue areas (myelinated fibers) and red areas (neuronal bodies) as well as the total area of each section. Derived measures (average ischemic area, and partial and approximated ischemic volumes) were also obtained from the ischemic groups. RESULTS: The animal homeostasis parameters remained within acceptable limits for this type of experiment. Regarding the myelinated areas (blue) there was no significant difference between groups C vs. S (p=0,39, Mann-Whitney-Wilcoxon), IC vs. IH3 (p=0,85, Mann-Whitney-Wilcoxon), and IH1 vs. IH2 (p=0,63, Mann-Whitney-Wilcoxon), and there was statistical difference between groups C vs. IC (p=0,0001, Mann-Whitney-Wilcoxon), IC vs. IH1 (p=0,01, Mann-Whitney-Wilcoxon), and IC vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). Regarding the neuronal bodies areas (red) there was no significant difference between groups C vs. S (p=0,48, Mann-Whitney-Wilcoxon), IC vs. IH3 (p=0,27, Mann-Whitney-Wilcoxon), and IH1 vs. IH2 (p=0,68, Mann-Whitney-Wilcoxon), and there was significant difference between C vs. IC groups (p=0,0001, Mann-Whitney-Wilcoxon), IC vs. IH1 (p=0,009, Mann-Whitney-Wilcoxon), and IC vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). Statistical analysis of average ischemic areas, and partial and approximated volumes of ischemic regions showed no significant difference between groups IC vs. IH3 (p=0,57, Mann-Whitney-Wilcoxon), and IH1 vs. IH2 (p=0,79, Mann-Whitney-Wilcoxon), and showed statistical difference between groups IC vs. iH1 (p = 0,0001, Mann-Whitney-Wilcoxon), and IC vs. IH2 (p = 0,0011, Mann-Whitney-Wilcoxon). CONCLUSIONS: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.

Lin, Wenhua. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 162-190). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Há décadas os campos magnéticos (CMs) são alvo de investigação científica. Entretanto, o grande corpo de evidências, está relacionado a campos eletromagnéticos e não a campos magnéticos contínuos. Nosso interesse é direcionado para a modulação das respostas comportamentais e motoras, na preservação de neurônios pós-lesão isquêmica e na possibilidade de uma interferência funcional com drogas que modifiquem a neurotransmissão encefálica. Utilizamos 130 Gerbilos, alocados em 13 grupos experimentais. Grupos específicos foram submetidos a isquemia encefálica global bilateral e a implantação de um capacete magnético com potencia de 3200G. Quatro dias após os procedimentos cirúrgicos os animais foram avaliados no monitor de atividades e no Rotarod, após receberem uma injeção de Apomorfina (APO) (2,5mg /kg) ou Racloprida (RAC) (0,9ml/kg). Valor de p significativo <0,05. No monitor de atividades, os animais do grupo isquemia atravessaram o maior número de sensores horizontais (F12,117: 9,39) e verticais (F12,117: 10,60) do que todos os outros grupos. Animais isquêmicos injetados com APO e tratados com campo magnético atravessam um número menor de sensores do que os grupos isquêmicos. Os isquêmicos injetados com APO e estimulados com o polo norte dispararam menos sensores do que os isquêmicos injetados com APO. Animais injetados com RAC com ou sem estimulação magnética disparam menos sensores do que os animais isquêmicos e isquêmicos tratados com polo norte e sul. No teste do Rotarod, o grupo isquêmico apresentou o menor tempo de permanência no teste do que os demais grupos. Ainda, animais isquêmicos tratados com APO e RAC e estimulação magnética pelo polo norte apresentam maior tempo de permanência em relação aos grupos isquemia e isquemia injetado com Apo e RAC (F12,117: 11,29). Nossos dados confirmam a possibilidade de interação dos polos magnéticos e os mecanismos de ação das drogas utilizadas no experimento. / For decades, magnetic fields (CMs) have been the subject of scientific research. However, the great body of evidence is related to electromagnetic fields and not to continuous magnetic fields. Our interest is directed to the modulation of behavioral and motor responses, the preservation of neurons after brain ischemic injury and the possibility of functional interference with drugs that modify brain neurotransmission. We used 130 gerbils, allocated in 13 experimental groups. Specific groups were submitted to bilateral global brain ischemia and the implantation of a magnetic helmet with power of 3200G. Four days after the surgical procedures, the animals were evaluated on the activity monitor and Rotarod after receiving an injection of Apomorphine (APO) (2.5 mg / kg) or Raclopride (RAC) (0.9 ml / kg). Significant p value was set as <0.05. In the activity monitor, the animals in the ischemia group crossed fired the largest number of horizontal sensors (F12,117: 9,39) and vertical sensors (F12,117: 10,60) than all the other groups. Ischemic animals injected with APO and magnetic field fired a smaller number of sensors than the ischemic groups and injected with APO. Animals stimulated with the north pole fired fewer sensors than ischemic animals injected with APO. RAC injected animals, with or without magnetic stimulation fired fewer sensors than ischemic animals or ischemic with north and south magnetic stimulation. In the Rotarod test, the ischemic group had the shortest permanence time in the test than the other groups. Still, ischemic animals treated with APO and RAC and North Pole magnetic stimulation present a longer permanence time in comparison to the ischemia group and ischemia with APO and RAC. Ischemic animals injected with APO and magnetic field pass through a smaller number of sensors than the ischemic groups and injected with APO. In the Rotarod test, the ischemic group had the shortest residence time in the test than the other groups. Still, ischemic animals treated with APO and north pole present a longer residence time in relation to the ischemia groups with APO and RAC (F12,117: 11,29). Our data confirm the possibility of interaction of the magnetic poles and the action mechanisms of action of the drugs used in the experiment.