Studies on molecular and pathophysiological mechanisms in age related brain disease

对老年性脑病的分子和病理生理机制进行了2年(2002-2003)的研究，结果如下：1)病理生理机制和自由基：自由基，尤其是羟基自由基，通过钙内流和细胞膜电压依赖性钙通道的紊乱，与神经细胞死亡密切相关。2)老年性脑病的分子基础分析：对PET和MR1图像进行配准，建立评价血流和/或糖代谢区域的方法。与临床健康犬相比，痴呆犬表现出脑血流和葡萄糖代谢的减少，尤其是皮质。在组织病理学检查中，包括野生动物在内的几乎所有被检查的动物都显示出老年斑和血管周围的淀粉样蛋白沉积，与老年人的情况相似。这些组织病理学结果明显与年龄增加有关。此外，还进行了视觉诱发电位(VEP)检查。老年Beagle犬的P2潜伏期随年龄增大而延长，VEP被认为是诊断老年性脑病的有效工具。3)老年性脑病动物模型：采用大鼠脑内注射氯化铁复制反复发作的自发性癫痫模型。所有注射的大鼠在治疗后4个月均出现癫痫发作。脑组织中天冬氨酸、谷氨酸、牛磺酸和GABA的浓度降低，但其病理生理效应尚未完全阐明。

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.