Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 6 uppsatser.

L’ischémie cérébrale est caractérisée par une interruption totale ou partielle de l’apport sanguine au cerveau, conduisant à une privation d’oxygène et de glucose pour les cellules du cerveau. La série de processus cellulaires qui sont déclenchées par une ischémie cérébrale sont nombreux et complexes. La réduction sévère d’oxygène et de glucose la diminution de la production d’ATP et un changement drastique de la concentration de K+, du pH intracellulaire et extracellulaire et de la production de lactate. La perturbation du métabolisme énergétique au sein des tissus ischémiés conduit rapidement à la dépolarisation membranaire et au relarguage de neurotransmetteurs dans le milieu extracellulaire. Dans le cervelet, l’impact d’un stress ischémique à largement été étudié sur les cellules de Purkinje, seule voie de sortie neuronale du cortex cérébelleux. Il a été montré que le glutamate, relargué par une surexcitation des fibres glutamatergique et par l’inversion des transporteurs du glutamate, est la cause principale de la dépolarisation anoxique des cellules de Purkinje. Cependant, la compréhension de la réponse astrocytaire et l’influence des astrocytes vis-à-vis de l’ischémie ne sont pas encore connu.La cellule de Bergmann est un astrocyte radiaire qui compose un réseau couplé électriquement, formant des interactions anatomiques et fonctionnelles complexes avec les neurones du cortex cérébelleux. En utilisant un modèle in vitro d’ischémie cérébrale, la privation d’oxygène et de glucose (OGD), plusieurs caractéristiques de base de la réaction astrocytaire à l'ischémie sont analysés. Des expériences en patch clamp et d’imagerie calcique sont réalisées sur tranche de cervelet adulte révélant la réponse de la glie de Bergmann à l’OGD par une dépolarisation progressive de la membrane, avec en parallèle une augmentation de calcium cytosolique soutenue. L’enregistrement apparié entre cellule de Purkinje et cellule de Bergmann révèle des différences importantes de réponse à l’OGD entre ces deux types cellulaires. De plus, nous avons mesuré les changements de la concentration de K+ extracellulaire durant l’OGD en utilisant des microélectrodes sensibles aux ions. Nos résultats montrent une corrélation importante entre la dynamique du K+ extracellulaire et la dépolarisation membranaire de la cellule de Bergmann au cours de l’OGD. / Cerebral ischemia is characterized by partial or total interruption of the blood supply to the brain resulting in glucose and oxygen deprivation to brain cells. The series of cellular processes that are unleashed by cerebral ischemia are complex. The severe reduction in oxygen and glucose induces decreases in ATP production and dramatic changes in extracellular K concentration, pH of intracellular and extracellular space and lactate production. The disruption of energy metabolism in the ischemic tissue rapidly lead to membrane depolarisation and neurotransmitters are released into the extracellular space. In the cerebellum, the impact of an ischemic stress has been extensively studied in Purkinje cells, the only neuronal output of the cerebellar cortex. It has been shown that glutamate released from overexcited fibers and from reversal of glutamate transporters, is the principal cause of the dramatic, anoxic depolarization in Purkinje cells. However a detailed understanding of the astrocytic response to cerebellar ischemia and the potential influence of astrocyte to ischemia outcome is still lacking.Bergmann glia (BG) are radial gial cells that form networks of electrically coupled cells underling complex anatomical and functional interactions with the neurons of the cerebellar cortex. Using an in vitro model of cerebral ischemia, the oxygen and glucose deprivation (OGD), several basic features of astrocytic reaction to ischemia are analyzed. Patch clamp and calcium imaging experiments performed in cerebellar slices from adult mice revealed that BG respond to OGD with a progressive membrane depolarisation that is paralleled with a sustained cytosolic calcium increase. Double patch-clamp recordings between Purkinje neurons and BG reveal different responses to OGD in these cell types. Furthermore, we measured extracellular potassium concentration changes during OGD by using ion-sensitive microelectrodes. Our results indicate an important correlation between the BG membrane depolarisation and the extracellular K dynamics during OGD.

Cerebral ischemia is defined as a decrease in blood flow to the brain. It is most often caused by obstruction of a cerebral blood vessel, and is recognized by the World Health Organization as the leading cause of serious adult disability and one of the top three causes of adult death worldwide. Most survivors demonstrate partial restitution of function over time, but the underlying recovery mechanism(s) remain unclear especially in a subset of patients with persistent neurological morbidities despite normal-appearing brain on neuroimaging. The optimal way to understand any human disease state is via clinical studies. Unfortunately, well-controlled experiments in humans are difficult due to small patient populations, the presence of numerous confounding variables, and ethical issues associated with invasive or discomforting experimental procedures. Anesthetized animal models of cerebral ischemia afford a means of avoiding the above difficulties. However, anesthesia and physiological perturbations that occasionally follow brain ischemia may affect the reliability of certain tools used to study this disease, such as functional magnetic resonance imaging (fMRI). Therefore, the central goals of this thesis were: 1) to evaluate the feasibility of performing fMRI in anesthetized and awake animals, 2) to assess fMRI responses under various perturbations of cerebral perfusion and tissue oxygenation in order to identify key factors that may modulate functional signal changes following ischemia, and 3) to utilize fMRI, behavioral tests and histology in an anesthetized animal model of transient focal cerebral ischemia to explore postischemic changes in brain pathology/function and how they relate to changes in behavior. In the first study of this dissertation, I report the evaluation of fMRI responses in anesthetized and awake animals. Anesthesia is frequently used in animal models of cerebral ischemia, but is known to alter brain perfusion and metabolism which may, in turn, affect fMRI responsivity. Perfusion-based fMRI was used to evaluate cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) responses to hypercapnia in awake and isoflurane-anesthetized rats. Hypercapnia produced significant CBF and BOLD fMRI signal changes throughout the cerebrum in awake and isoflurane-anesthetized groups. These results show that perfusion-based fMRI can successfully detect stimulus-evoked hemodynamic changes in the brains of both conscious and isoflurane-anesthetized animals. The second study of this dissertation: 1) investigates the effects of alterations in cerebral perfusion and oxygenation on fMRI signal changes, and 2) examines the self-consistency of an imaging-based formalism for the calculation of the cerebral metabolic rate of oxygen (CMRO2). Functional MRI responses to a stimulus can be described in terms of relative or absolute signal change. A relative fMRI response is defined as a percent-change relative to its own respective baseline value. An absolute fMRI response is defined as a quantitative change relative to a single fixed baseline value that serves as a control. Thus, an absolute fMRI signal change is largely independent of the baseline state and may more accurately index brain activity when baseline fMRI signals change significantly over time due to, for example, hemodynamic-metabolic disturbances that occur during and/or after brain ischemia. To address these issues, the effects of inspired hypoxic, normoxic, hyperoxic, and hypercapnic gases on baseline and forepaw stimulation-evoked changes in BOLD and CBF fMRI signals were examined in isoflurane-anesthetized rats. Relative fMRI responses to forepaw stimulation varied-whereas. absolute responses were similar--across gas conditions. These results demonstrate that absolute measurements of fMRI signal change may lend a more accurate measure of brain activity during states of altered basal physiology as well as support the self-consistency of the imaging-based CMRO2 formalism under these conditions. The third and last study of this dissertation utilized multimodal MRI, behavioral tests, and histology at acute to chronic periods following transient middle cerebral artery occlusion (tMCAO) in the rat to examine the evolution of pathological, functional, and behavioral parameters following transient focal cerebral ischemia. MRI was used to track the evolution of brain pathology and function following cerebral ischemia, and it was found that the cerebral sensorimotor network, critical for sensory and motor behavioral functions, showed profoundly abnormal signal changes that required up to one day to normalize. Adhesive removal, forepaw placement and beam-walk behavioral tests demonstrated sensorimotor dysfunctions that gradually improved but remained long after the recovery of MRI parameters. Postmortem histology confirmed the presence of selective neural cell death within the sensorimotor network at time points when behavior was abnormal. These results suggest that subtle postischemic pathological changes in the brain undetectable by MRI may be responsible for persistent behavioral deficits-a finding which may be relevant to a clinical subset of patients with persistent neurological morbidities despite negative MRI results following cerebral ischemia.

<p>UVOD: Vilisov poligon predstavlja najznačajniju rezervu kolateralnog protoka između ekstrakranijalnih arterija koje vaskularizuju mozak i ima sposobnost razvoja kolateranih puteva kod ekstrakranijalne karotidne bolesti. Ova anatomska struktura podložna je varijacijama koje uključuju i prekid kontinuiteta i nekompletnost kolateralizacije. CILJEVI: Cilj je bio da se utvrdi da li nekompletnost Vilisovog poligona utiče na če&scaron;će pojavljivanje neurolo&scaron;ke simptomatologije i ishemijske moždane lezije kod pacijenata sa ekstrakranijalnom karotidnom bolesti. Takođe cilj je bio i da se utvrdi da li cerebrovaskularna reaktivnost kod pacijenata sa asimptomatskom ekstrakranijalnom karotidnom bolesti zavisi od kompletosti Vilisovog poligona i na koji način hirur&scaron;ki tretman utiče na parametre cerebrovaskularne rezerve kod pacijenata sa kompletnim i nekompletnim Vilisovim poligonom. METOD: U retrospektivnoj studiji analiziran je nalaz MRA kod 211 pacijenata sa ekstrakranijalnom karotidnom bolesti i 102 pacijenta iz kontrolne grupe. U prospektivnoj studiji je kod 98 pacijenata sa asimptomatskom karotidnom bolesti pored MRA nalaza određivana cerebrovaskularna reaktivnost putem određivanja &bdquo;breath hold index&ldquo;-a (BHI) pre i nakon operativnog tretmana. REZULTATI: Nekompletan Vilisov poligon nađen je kod 25% asimptomatskih, 47,5% simptomatskih pacijenata sa karotidnom bolesti i kod 59% kontrolne grupe pacijenata, pri čemu su se razlike pokazale kao statistički značajne. Kod asimptomatskih pacijenata sa nekompletnim Vilisovim poligonom BHI preoperativno iznostio je 0,62 a postoperativno 1,01 na strani lezije. U slučaju nekompletnog Vilisovog poligona preoperativna vrednost BHI iznostila je 0,88 a postoperativna 1,09 na strani lezije. Razlike su se pokazale kao statistički značajne između grupa i pre i posle operativnog tretmana. Porast je bio statistički značajno izraženiji u grupi asimptomatskih pacijenata sa nekompletnim Vilisovim poligonom. Nisu zabeležene major operativne komplikacije (perioeprativni moždani udar,smrtni ishod) a na pojavu hiperperfuzionog sindroma najvi&scaron;e su uticali kompletnost Vilisovog poligona, vrednost BHI i preoperativni tretman hipertenzije. ZAKLJUČCI: Nekompletan Vilisov poligon predstavlja faktor rizika za pojavu neurolo&scaron;ke simptomatologije ili ishemijske moždane lezije kod pacijenata sa ekstrakranijalnom karotidnom bolesti. Kod asimptomatskih pacijenata nekompletan Vilisov pologon utiče na smanjenu cerebrovaskularnu reaktivnost i veći rizik od moždanog udara. Parametri cerebrovaskularne reaktivnosti signifikantno se pobolj&scaron;avaju nakon operativnog tretmana.</p> / <p>INTRODUCTION: Circle of Willis is the most important reserve of collateral flow between the extracranial arteries that supply the brain and has the ability to develop collateral pathways in extracranial carotid disease. This anatomical structure is subject to variations which include a disruption in the continuity and incompleteness of collateralisation. OBJECTIVES: was to determine whether the incompleteness of the Circle of Willis is more often associated with neurological symptoms and ishemic cerebral lesions in patients with extracranial carotid artery disease. Also, the objective was to determine whether cerebrovascular reactivity in patients with asymptomatic extracranial carotid artery disease depends on the completeness Circle of Willis and how surgical treatment affects the parameters of cerebrovascular reserve in patients with complete and incomplete Circle of Willis. METHODS: This study analyzed the findings of MRA in 211 patients with extracranial carotid artery disease and 102 patients in the control group. In prospective study in 98 patients with asymptomatic carotid artery disease in addition to the MRA findings cerebrovascular reactivity was determined by determining the &quot;breath hold index&quot; -a (BHI) before and after surgical treatment. RESULTS: Incomplete Circle of Willis was found in 25% of asymptomatic, 47.5% of symptomatic patients with carotid artery disease, and 59% of the control group patients, where the difference proved to be statistically significant. In asymptomatic patients with incomplete Circle of Willis BHI values were 0.62 preoperatively and 1.01 postoperatively on the side of the lesion. In the case of incomplete Circle of Willis preoperative BHI values were 0.88 preopertively and 1.09 postoperatively in asymptomatic patients. The differences are shown to be statistically significant between the groups before and after surgical treatment. The increase was significantly more pronounced in the group of asymptomatic patients with incomplete Circle of Willis. There were not recorded major operative complications (perioeprativni stroke, mortality) and the occurrence hyperperfusion syndrome was most affected by completeness of the Circle of Willis, a value BHI and preoperative treatment of hypertension. CONCLUSIONS: Incomplete Circle of Willis is a risk factor for the occurrence of neurological symptoms or ischemic brain lesions in patients with extracranial carotid artery disease. In asymptomatic patients incomplete Circle of Willis affects the reduced cerebrovascular reactivity and a higher risk of stroke. The parameters of cerebrovascular reactivity significantly improved after surgical treatment.</p>

L’injection intraveineuse de l’activateur tissulaire du plasminogène (tPA) est le seul traitement aigu de l’ischémie cérébrale autorisé chez l’Homme. Cependant, la thrombolyse présente des limites d’utilisation, comme son étroite fenêtre thérapeutique, un risque hémorragique et une efficacité de recanalisation malgré tout relativement peu élevée. De plus, la littérature suggère fortement que non seulement le tPA endogène, mais aussi exogène (capable de traverser la barrière hémato-encéphalique), a des effets pro-excitotoxiques. Nous avons proposé que cet effet résulte du clivage de la sous unité NR1 du récepteur NMDA. Malgré un effort important de la communauté scientifique pour chercher de nouveaux traitements, tous les espoirs se sont avérés être des échecs. Sur ces bases, ces travaux de thèse ont consisté à : 1) Améliorer les approches précliniques en développant un nouveau modèle d’ischémie cérébrale chez la souris et en incluant dans les études un des principaux facteur de risque des AVC, le vieillissement ; 2) Développer une stratégie d’immunothérapie visant l’interaction tPA/ récepteur NMDA. J’ai ainsi montré qu’il existe une diminution du volume de lésion ischémique corrélée à l’âge et que cette diminution de tPA est due à une diminution d’expression du facteur de transcription D-Site Albumin Binding Protein (DBP). J’ai également développé un modèle innovant d’ischémie thrombo-embolique chez la souris, dans lequel la reperfusion par le tPA est bénéfique, si tant est qu’elle soit réalisée de manière précoce. Sur ce modèle, j’ai apporté par une stratégie d’immunisation active la preuve in vivo du clivage du domaine amino-terminal de la sous-unité NR1 des récepteurs NMDA. Enfin, j’ai produit un anticorps médicament, capable d’empêcher l’interaction du tPA avec la sous-unité NR1 des récepteurs NMDA, dont une injection unique permet de réduire les lésions ischémiques, mais aussi d’augmenter la fenêtre thérapeutique de la thrombolyse, conférant alors une récupération fonctionnelle à long terme. Cette stratégie pourrait donc accroître la proportion de patients traitables après un AVC ischémique aiguë / Reperfusion with tissue plasminogen activator (tPA) is the only approved treatment for ischemic stroke. However, thrombolysis has some limitations, including a narrow therapeutic window, an elevated risk of hemorrhage transformation and a low level of effective recanalization. Moreover, there is a growing body of evidence that both endogenous and exogenous tPA (able to cross the blood-brain barrier) could mediated pro-excitotoxic effects. We have proposed that this noxious effect results from the cleavage of the NR1 subunit of the NMDA receptor. My thesis work consisted in: 1) Improving pre-clinic approaches by developing a new model of thrombo-embolic ischemia in mice and by taking into account a major risk factor for stroke, aging; 2) Developing a strategy of immunotherapy targeting the interaction between tPA and NMDA receptor. I have thus shown that ischemic lesions decrease as a function of age, due to reduced levels of tPA. Moreover, I have identified DBP (D-site albumin Binding Protein), as being the transcription factor responsible for the control of tPA levels as a function of age. I have also developed a new model of thrombo-embolic ischemia in mice, in which tPA-induced thrombolysis is beneficial, provided it is performed soon enough. In this model, I have demonstrated by using a strategy of active immunization the in vivo occurrence of the cleavage of the NMDA receptor NR1 subunit by tPA. Finally, I have produced an antibody able to prevent the interaction between tPA and the NMDA receptor subunit, of which a single injection confers long lasting brain protection and neurological recovery and can also increase the therapeutic window of thrombolysis. This strategy could thus significantly increase the proportion of treatable ischemic stroke patients

Xian, Jiawen. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 201-230). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

<p>UVOD: Akutni ishemijski moždani udar (AIMU) je poremećaj moždane funkcije nastao usled vaskularnih o&scaron;tećenja, uzrokovane okluzijom ili embolijom krvnog suda. Za razliku od standardnog CT pregleda endokranijuma, CT perfuzija (CTP) je napredna dijagnostička procedura koja može u prvim satima od početka simptoma AIMU pružiti precizne informacije o lokalizaciji i veličini infarkta mozga, a u okviru infarkta, razlikovati srž i ishemijsku penumbru. Samim tim, CTP predstavlja svojevrsnu pomoć u selekciji pacijenata za intravensku primenu rekombinantnog tkivnog plazminogen aktivatora (rtPA). CILJ RADA: Cilj istraživanja je bio da se primenom CTP ispita koliko iznosi: optimalna veličina srži, zatim minimalni i optimalan odnos penumbre i srži infarkta pogodnih za primenu rtPA, maligni profil srži infarkta koji je nepogodan za primenu rtPA i % simptomatske hemoragije kao komplikacije nakon rtPA. MATERIJAL I METODE: Istraživanje je obavljeno u Specijalnoj bolnici &bdquo;Sveti Sava&ldquo; u Beogradu kao petogodi&scaron;nja retrospektivna studija. Studija je obuhvatila ukupno 130 pacijenata sa AIMU kod kojih je primenjena CTP. Eksperimentalnu grupu je sačinjavalo 100 pacijenata kojima je aplikovana rtPA, a kontrolnu grupu 30 pacijenata, koji nisu primili rtPA. Svim ispitanicima su načinjeni: standardni CT pregled glave i CT perfuzija odmah nakon prijema i kontrolni standardni CT pregled endokranijuma 24 h nakon prijema u bolnicu. Pregledi su obavljeni sa 16-slajsnom MSCT aparatu, pri čemu je pokrivenost CTP iznosila 2 cm. &bdquo;Mismatch&ldquo; postoji ukoliko je perfuziona lezija na CBF mapi veća od perfuzionog deficita na CBV mapi (srţ infarkta). REZULTATI: Rezultati studije su pokazali da pacijenti oboleli od AIMU sa mismatchom manjim od 20% nisu imali koristi od primenjene rtPA, a pacijenti sa 20% i vi&scaron;e mismatch-om su imali ili umeren ili značajan neurolo&scaron;ki oporavak. Optimalni mismatch, kojim se postiže visoka uspe&scaron;nost nakon rtPA je iznosio ˃ 101% penumbre. Pacijenti sa povr&scaron;inom perfuzionog deficita na CBV mapi manjom od 1175 mm2 su imali bolji neurolo&scaron;ki oporavak, u odnosu na pacijente savećim lezijama, a samim tim su bili pogodni za primenu rtPA. Perfuzioni deficit na CBV mapi veći od 3000 mm2 (60ml) je predstavljao maligni profil infarkta, usled povećanog rizika od nastanka simptomatske hemoragije i smrtnog ishoda. Simptomatska hemoragija u eksperimentalnoj grupi je iznosila svega 3%, &scaron;to predstavlja nizak procenat komplikacija nakon reperfuzione terapije. ZAKLJUČAK: CT perfuzija je urgentna i brza tehnika, koja nam daje jedinstvene informacije o AIMU, pomaže u dono&scaron;enju odluke o terapijskom pristupu i može poslužiti kao surogat biomarker u predikciji kliničkog ishoda.</p> / <p>INTRODUCTION: Acute ischemic stroke (AIS) is functional brain disorder, which is happened due to vascular damaged, caused by vessel occlusion or embolism. Unlike to noncontrast brain CT, CT perfusion (CTP) is advanced diagnostic procedure, which could give accurate information about localization and extent of AIS in the first hours of symptom onset, and also differentiate infarct cor and ischemic penumbra. Thus, CTP helps in selection patients for administration intravenous recombinant tissue plasminogen activator (rtPA) AIM: The aims of study were to estimate: the size of optimal infarct cor, minimal and optimal ratio between penumbra and infarct core which is suitable for rtPA, malignant profile of infarct core which is not suitable for rtPA and percentage of symptomatic intracerebral hemorrhage as compli-cation after rtPA using CTP. MATERIAL AND METHODS: The investigation was performed in Stroke hospital &bdquo;Sveti Sava&rdquo; in Belgrade as five years retrospective study. Study included 130 patients with AIS with performed CT perfusion. One hundred patients from experimental group were treated with rtPA and thirty patients from control group were not treated with rtPA. All patients underwent baseline noncontrast CT of brain, CT perfusion and control 24 hours follow-up noncontrast brain CT. Examinations were done on 16-slice MSCT and CTP covered an area of 20 mm of brain tissue. &bdquo;Mismatch &ldquo;was defined as a perfusion lesion (CBF lesion) larger than the core lesion (CBV). RESULTS: Results of study showed that the patients with AIS and mismatch less than 20%, had no benefit from rtPA, but patients with &ge; 20% of mismatch had good or excellent clinical outcome. Optimal mismatch, which provided favorable response after rtPA, was ˃101% of penumbra. Patients with cor perfusion lesion (CBV) less than 1175 mm2, are suitable for rtPAand had better clinical outcome, then the patients with larger lesions. Perfusion cor lesions (CBV) larger than 3000 mm2 (60ml) was malignantprofile, because of high risk of symptomatic intracerebral hemorrhage and mortality. Symptomatic hemorrhage in experimental group was only 3%, as a low percentage of complications after reperfusion therapy.<br />CONCLUSION: CTP is emergency and rapid technique, which provides unique information about AIS, helps with clinical decision making and could be surrogate biomarker in prediction of clinical outcome.</p>

Baicalin, which is a flavonoid, was previously shown to exert neuroprotective effects against ischemic injury and oxidative insults. In this study, baicalin was found to induce neuronal differentiation on both C17.2 NSC and primary mouse NSC originated from hippocampuses of E14.5 mouse embryos. The baicalin-mediated differentiation of C17.2 NSC was noted in dose- and time-dependent manners. Baicalin-treated NSC displayed long processes of neurites. The gene expression of neuronal markers, NF-L, TUBB3 and MAP2 was also significantly increased after treated with 20 to 50 muM baicalin on C17.2 NSC. Treating C17.2 NSC with baicalin significantly increased the number of TUBB3 positive cells by 300%. A significant increase in the gene expression of TUBB3 was also observed on primary NSC upon baicalin treatment at 5 to 10 muM. The number of TUBB3 positive cells was increased by 100% after treating with 10 muM baicalin. C17.2 NSC treated with baicalin also increased the gene expression of GABAergic and serotonergic neuronal subtype specific enzymes GAD1 and TPH1. / Nature provides a vast pool of natural compounds with neuroprotection and neurotrophism. A few of these compounds can induce the differentiation of neural stem cells (NSC). There are ample opportunities to discover more natural compounds with differentiation inducing effect on NSC. One of the objectives of this project is to look for novel natural compounds showing neurogenic effect on NSC. This project has established a platform for screening medicinal materials and natural compounds with neural differentiation promoting effect on C17.2 mouse neural stem cell line. Screening results identified total Sanqi saponins, total Renshen saponins, Huangqin extracts and baicalin as potent candidates for inducing this differentiation of NSC. / This project also aims at characterizing the mechanisms involved in the neuronal differentiation effect of baicalin on NSC. Annotation from microarray analysis indicated that baicalin treatment on C17.2 NSC is related to development of tissue and nervous system. qPCR study attested the increased gene expression of nerve growth factor-beta, neurotrophin-3, pro-neural transcriptional factors Ngn1, Ngn2 and NeuroD2. Western blotting showed that baicalin activated ERK1/2 MAP kinase but not JNK and p38 MAP kinases. / This project demonstrated the neurogenic potential of natural resources on NSC. A novel neuronal induction effect of baicalin on NSC was also demonstrated with its mechanisms characterized. This project also revealed that baicalin can be used for promoting functional recovery of post-ischemia animals. / This study showed for the first time that baicalin exerts neuronal differentiation inducing effect on NSC. Another objective of this project is to study whether baicalin can promote functional recovery of animals with ischemia brain injury. Mice having undergone transient occlusion of the bilateral common carotid arteries with blood-reperfusion to induce global cerebral ischemia were treated with baicalin and/or EGFP-NSC. Ischemia animals received implantation of EGFP-NSC into the caudate putamen and/or intravenous injection of baicalin on alternate days for two-week on day seven post-ischemia displayed significant improvement of the cognitive function in terms of the incident of error and escape time in the water T-maze task compared to the control arm of ischemia mice. Data of the study suggested that the therapeutic effect of baicalin would be comparable to that of neural stem cell transplant in improving the cognitive function in a mouse ischemic stroke model. / Li, Ming. / Adviser: P. C. Shaw. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 199-232). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Han, Jinghao. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 182-204). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.