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

以期阐明颅脑损伤后认知功能障碍的病理生理机制。根据磁共振成像(MRI)将52例轻型颅脑损伤患者分为3组。调查结果。PET测定局部脑血流量(CBF)、氧摄取分数(OEF)和脑氧代谢率(CMRO2)。采用韦氏成人智力量表(WAIS-R)评定较高的皮质功能障碍。我们的结论是，较高的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后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，并用浸银方法观察了弥漫性脑损伤后组织学变化。定量评估显示，在实验过程中，大脑脚处暗轴突的数量增加。我们发现大鼠弥漫性脑损伤后轴突进行性变性。变性神经元内有活化的小胶质细胞渗入。对活化的小胶质细胞进行p38丝裂原活化蛋白激酶(MAPK)的磷酸化检测。激活的小胶质细胞产生脑源性神经营养因子(BDNF)，但BDNF的量不足以挽救变性神经元。此外，我们还检测了大鼠脑损伤后髓脑特异性蛋白水解酶(MSP)的表达。MSP基因是激肽释放酶基因中的一员，在大鼠体内主要在中枢神经系统表达。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周转有关。活性MSP的调节可能在重新髓鞘形成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.