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

为了阐明外伤性脑损伤后认知功能障碍的病理生理机制。将52例轻度创伤性脑损伤患者根据磁共振成像（MRI）分为3组。发现。PET检测脑区域血流量（CBF）、氧提取分数（OEF）、脑氧代谢率（cro2）。使用韦氏成人智力量表（WAIS R）评估高级皮质功能障碍。我们的结论是，高级皮质功能障碍的严重程度与CMR02的降低有关。为了阐明弥漫性脑损伤组织学变化的时间模式，我们建立了大鼠弥漫性脑损伤模型，采用银浸渍法对弥漫性脑损伤后的组织学变化进行了检测，选择性地展示了神经元的塌陷。定量评价显示，在实验期间，脑梗暗轴突数量增加。我们发现大鼠弥漫性脑损伤后轴突进行性退化。活化的小胶质细胞浸润于退化的神经元。检测活化小胶质细胞p38丝裂原活化蛋白激酶（MAPK）的磷酸化水平。被激活的小胶质细胞产生脑源性神经营养因子（BDNF），但BDNF的量不足以挽救退行性神经元。我们还检测了大鼠脑损伤模型后髓脑特异性蛋白酶（MSP）的表达。MSP基因是激肽激酶基因的一个成员，在大鼠中主要在中枢神经系统表达。MSP主要在少突胶质细胞中表达。我们认为MSP的表达可能与脑损伤后髓磷脂相关蛋白和细胞外基质蛋白的周转有关。活性MSP的调节可能在涉及髓鞘再生或脱髓鞘的生理或病理变化中起重要作用。

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.