Studies on molecular and pathophysiological mechanisms in age related brain disease

对年龄相关脑疾病的分子和病理生理机制进行了为期2年（2002-2003）的研究，得到了以下结果：1)病理生理机制和自由基：自由基，尤其是羟基自由基，通过钙内流干扰细胞膜电压依赖性钙通道，与神经细胞死亡密切相关。在缺血状态下，神经元细胞的主要代谢，如高能磷酸盐成分的降解，显著增加，自由基的产生。2)年龄相关性脑疾病的分子碱基分析：将PET与MR1图像进行配准，建立血流和/或葡萄糖代谢区域的评价方法。与临床健康的狗相比，痴呆狗的血流量和大脑，尤其是皮质的葡萄糖代谢都有所减少。在组织病理检查中，几乎所有的动物包括野生动物都显示老年斑和血管周围淀粉样蛋白沉积，就像老年人一样。这些组织病理学结果与年龄明显相关。同时进行视觉诱发电位（VEP）测定。随着年龄的增长，老年Beagle犬的P2潜伏期延长（峰值2），VEP被认为是诊断老年脑部疾病的有效工具。3)老年性脑病动物模型：采用大鼠脑内注射氯化铁建立复发性自发性癫痫模型。治疗4个月后，所有大鼠均出现癫痫发作。脑内天冬氨酸、谷氨酸、牛磺酸和GABA的浓度下降，但其病理生理作用尚未完全阐明。

Molecular and pathophysiological mechanisms in age related brain disease were investigated for 2 years (2002-2003) and following results were obtained.1)Pathophysiolosical mechanisms and free radicals : Free radicals, especially hydroxyradical, were closely related to neurological cell death via Ca influx with a disturbance of voltage-dependent Ca channels in cell membrane. Prine metabolism, such as degradation of high energy phophate components, was remarkably increased and generation of free radicals was developed in neuronal cells during the ischemic condition.2)Molecular bases analysis for age related brain disease : Registration between PET and MR1 images was carried out and the method of it was established for evaluating the regions of blood flow and/or glucose metabolism. Dementia dogs showed a decrease of blood flow and also glucose metabolism in brain, especially in cortex compared with, those in clinically healthy dogs. In histpathological findings, almost of all animals including wild animals examined showed senile plaque and perivascullar deposits of amiloid protein, like as those in aged man. Those histpathological findings were clearly associated with age advanced. In addition, visual evoked potentials (VEP) were also evaluated. Aged Beagle dogs showed a prolonged latency of P2 (peak 2) with age advanced and VEP was considered to be an available tool for diagnosis of aged brain disease.3) Animal model of aged brain disease : The recurrent spontaneous epileptic model was made an attempt to rats injected intracranially with iron chloride. All rats injected showed epileptic seizure by 4 months after the treatment. Concentrations of aspartate, glutamate, taurine, and GABA decreased in brain, however pathophysiological effects of those were not completely elucidated.