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The Role Of Hippocampal Neurogenesis In Experimental Epilepsy: It's Correlation With Epileptogenesis

Posted on:2005-06-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y C ChenFull Text:PDF
GTID:1104360122995791Subject:Neurology
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Epilepsy is a group of chronic disease characterized by recurrent episodic and central system dysfunction caused by abnormal discharge of neurons. It is a common neurological condition, which affects about 0. 5%-2% people worldwide. The ideas and hypothesis about the mechanism of epilepsy comes mostly from the observation of pathological changes and biochemistry action in epileptic brain. The common pathological changes in epileptic focus are (use the hippocampus as an example): neuron degeneration, death, lesions of the distributing of neuron dendrite, demission of synapse spine, proliferation of glia, and axon spouting of hippocampal granular cells. Therefore, most hypotheses of the mechanism in epilepsy were based on those appearances. The progress in understanding of the mechanism inepileptogenesis will be helpful in prevention and cure epilepsy.The study of neurogenesis in the adult brain is among the most exciting and fasting moving areas of neuroscience today. A series of evidence suggests that ongoing neurogenesis in discrete brain regions not only occurs in normal adult rats, but also in others mammalian animals, including humans. Some studies had shown that the neurogenesis could make changes on neuron plasticity in adult animal brains. The newly born DGCs appear to integrate both normally and abnormally into the existing hippocampal circuitry. These precursors proliferate in the dentate subgranular proliferative zone (SGZ) at the border of the granule cell layer and hilus, and their progeny migrate into the DGC layer where they differentiate into mature granule neurons. Those findings bring new hopes for the therapy of neurology disease, such as neurodegenerative disease and cerebral vascular diseases. New traces also were provided for study of mechanism of epileptogenesis in the brain structure and function plasticity aspect. There is significant value in investigating the mechanism of precursors proliferate in the brain and the function of the newly born neurons.The physiological role of persisting neurogenesis in brain is not clear today. The rate of newly born neurons in dentate gyrus can be influenced by some physiologicalfactors and pathological events, including aging, learning, environmental stimulation, glucocorticoid hormone levels, and glutamatergic input to the DGC layer etc. Furthermore, recent investigations using a variety of experimentally induced pathologies, including seizures, cerebral ischemia, and focal toxin injection, have identified significantalterations of DGC neurogenesis after brain injure.The hippocampus occupies an important role in the beginning and development of epileptic seizures, especially in partial seizures (eg. TLE). Studies accumulated over recent years suggested the damages following seizures or status epilepticus (SE) can lead to many changes in plasticity of hippocampus CA3 and dentate gyrus in rodents, including axon reorganization, activation of astrocyte, rebuilding of dendrite, and disseminate of granular cells layer, similar histological changes also seen in human mesial temporal lobe sclerosis. When seizures are induced in animal models, significant enhances in neurogenesis can be seen in dentate gyrus, and this kind of neurogenesis do not influenced by the mechanism of seizure (such as chemical or electrical stimulation evokes). Some evidences showed that those newly born neurons take part in the abnormity of structure and function in epileptic patients. However, the molecular mechanism between damages following seizures and the proliferation of newly born dentate gyrus granular cells is not clear. The property of precursor cell in neurogenesis is also undetermined. The neurogenesis in hippocampaldentate gyrus becomes a hot point which researchers take much interest in.In this study, we try to explore some issues above mentioned by using Li-Pilocarpine induced seizure model. It is an animal model having the similar characters with human partial epilepsy. Firstly, we established the experimental method to make this model, then we vis...
Keywords/Search Tags:Epilepsy, Hippocampus, Neurogenesis, Epileptogenesis, Pilocarpine, 5-bromodeoxyuridine, Apoptosis, Topiramate, X-ray
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