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Studies On The Protective Mechanisms Of Drugs For Activating Blood Circulation To Remove Blood Stasis In Ischemic Brain Injury

Posted on:2004-10-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:W J LiaoFull Text:PDF
GTID:1104360092496769Subject:Neurobiology
Abstract/Summary:PDF Full Text Request
Brain tissue has a relatively high consumption of oxygen and glucose, and depends almost exclusively on oxidative phosphorylation for energy production. Focal impairment of cerebral blood flow restricts the delivery of substrates, particularly oxygen and glucose, and impairs the energetics required to maintain ionic gradients. The energy failure leads to the development of a cascade of injury. Brain tissue damage following cerebral ischemia results from the interaction of complex pathophysiological process such as excitotoxicity, peri-infarct depolarizations, inflammation as well as programmed cell death. The structural and functional lesions are caused by these events. All four are potential targets for therapy. Stroke is caused by a disorder of blood flow in the brain and successful attempts to establish reperfusion early can reduce the magnitude and extent of tissue injury. The improvement of cerebral blood flow and neuroprotection are two basic principles of pharmacological intervention in acute stroke. Intervention will combine strategies that enhance both early reperfusion and neuroprotection.Maintain reperfusion timely and efficiently is one of the keys for the therapies, can rescue the brain tissue within ischemic penumbra, preparing for the tissue recovery. Huoxue Huayu (to activate blood circulation to remove blood stasis) is an important theory and a therapeutic principle in traditional Chinese medicine. It is unclear that the mechanisms of Huoxue Huayu drugs (drugs for activating blood circulation to remove blood stasis) on the neuroprotection in the ischemic brain injury, little studies on the imaging and cerebral metabolites, very a few studies on the angiogenesis, the direct protective effects is not elucidated for the cultured rat hippocampal neurons in hypoxia injury, little knowledge for the tissue repairing and neural regeneration.The present study chosen two kinds of Huoxue Huayu drugs, Angelica sinensis and Erigeron Breviscapus, investigated the protective effect of the Huoxue Huayu drugs for the ischemic brain injury in following six aspects, for the hippocampal neurons in hypoxia lesion, as well as potential effect for the neural regeneration, aims to elucidates the mechanisms of Huoxue Huayu drugs.Supported by the grants from the National Natural Science Foundation of China and National Key Laboratory of Spectroscopy, Atom and Molecule Physics. Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, we made the model for the ischemic brain injury in rats and cultured rat hippocampal neurons, used the means of measuring cerebral blood flow, magnetic resonance imaging and spectroscopy, ultrastructural identification, neuronal cell culture, immunohistochemistry. The cerebral blood flow and surface vessel density, cerebral metabolites N-acetyl aspartate (NAA), Choline (Cho) and creatine/phosphocreatine (Cr) in vivo, neurons and capillaries in cortex, the microscopic confocal Raman spectrum in cortex, the expression of neural cell adhesion molecules, and hippocampal neurons in hypoxia lesion are observed.The major results and conclusions are following:1. The Huoxue Huayu drugs reduced the size of infarct volume, increase the levels of metabolites within ischemic brain tissue, play the direct protective role in cerebral ischemia injury.2. The Huoxue Huayu drugs have the direct protective effects on the neurons in vivo.3. The Huoxue Huayu drugs restored the blood flow significantly, improved the blood circulation, and enhanced the development of angiogenesis.4. The Huoxue Huayu drugs have the direct protective effects on the cultured rat hippocampal neurons in vitro, inhibited the apoptosis, maintained the mitochondrial membrance potential, decreased the level of intracellular calcium within neuron.5. The Huoxue Huayu drugs enhanced the expression of neural cell adhesion molecule (NCAM), appeared to play a pivotal role in the neural regeneration.6. The Huoxue Huayu drugs has the comprehensive protective effect for the ischemic brain injury,...
Keywords/Search Tags:ischemic brain injury, Huoxue Huayu drugs (Drugs for activating blood circulation to remove stasis), cascade of injury, Angelica sinensis injection, Erigeron Breviscapus injection, surface vessel density, magnetic resonance imaging
PDF Full Text Request
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