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Prevention of neurodegeneration after head injury by activated maicroglia with antisense method

反义激活大胶质细胞预防颅脑损伤后神经退行性变

基本信息

批准号：
15591537
负责人：
AIHARA Noritaka
金额：
$ 1.92万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

In order to clarify after the pathophysiological of cognitive impairment after traumatic brain injury. Fifty-two patients with mild traumatic brain injury were devided into three groups based on magneteic resonance images (MRI). Findings. Regional cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were measured by PET. Higher cortical dysfunction was evaluated using Wechsler Adult Intelligence Scale-Revised (WAIS R). We concluded that the severity of higher cortical dysfmction is correlated with decrease of CMR02. To elucidated temporal pattern of histological changes in diffuse brain injury, we developed the rat diffuse brain injurt model We examined the histological changes after difi'use brain injury using silver impregnation method for selcive demonstration of collapsed neurons. Quantitative evaluation revealed that the number of dark axons at the cerebral peduncles invreased during the experimental peropd. We revealed that axon progressively degenerate after diffse brain injury in rat model. Activated microglia infiltrates in degenerated neuron. Activated microglia were evaluated phosphorylation of p38 mitogen-activated protein kinase (MAPK). Activated microglia produce Brain-deraived neurotrophic factor (BDNF), but the amount of BDNF is insufficient for the rescue of degenerarting neuron. We also examined the expression of myelencephalon-specific protease (MSP) after rat brain injury model. The gene of MSP is a member of the kallikrein gene fatnihy and in rats is expressed mainly in the central nervous system. MSP was expressed mainly in oligodendrocytes. We suggest that the expression of MSP may be related to turnover of myelin-associated proteins and extracelluar matrix proteins after brain injury. The regulation of active MSP may be important in the physiological or pathological changes involved in remyelination or demyelination.

以期阐明脑外伤后认知功能障碍的病理生理机制。对52例轻型颅脑损伤患者进行磁共振成像（MRI）检查，将其分为三组。调查结果。PET检测局部脑血流量（CBF）、氧摄取分数（OEF）和脑氧代谢率（CMRO2）。采用韦氏成人智力量表修订版（WAIS R）评估高级皮质功能障碍。我们得出结论，较高的皮质功能障碍的严重程度与CMR 02的降低相关。为阐明弥漫性脑损伤组织学变化的时间规律，我们建立了大鼠弥漫性脑损伤模型，用银浸渍法观察了弥漫性脑损伤后的组织学变化，以选择性显示神经元的塌陷。定量评价显示，实验期间大脑脚的暗轴突数量增加。结果表明，大鼠弥漫性脑损伤后轴突进行性变性。变性神经元内小胶质细胞浸润。检测活化的小胶质细胞p38丝裂原活化蛋白激酶（MAPK）的磷酸化水平。活化的小胶质细胞产生脑源性神经营养因子（BDNF），但BDNF的量不足以挽救变性神经元。我们还研究了大鼠脑损伤模型后中脑特异性蛋白酶（MSP）的表达。MSP基因是激肽释放酶基因家族的成员，在大鼠中主要表达于中枢神经系统。MSP主要表达于少突胶质细胞。我们认为MSP的表达可能与脑损伤后髓鞘相关蛋白和细胞外基质蛋白的转换有关。活化MSP的调节可能在髓鞘再生或脱髓鞘的生理或病理变化中起重要作用。