Studies on molecular and pathophysiological mechanisms in age related brain disease

本研究从分子水平和病理生理机制两个方面对年龄相关性脑疾病进行了2年（2002-2003年）的研究，主要结果如下：1）病理生理机制和自由基：自由基，尤其是羟自由基，通过Ca内流和细胞膜电压依赖性Ca通道的紊乱与神经细胞死亡密切相关。缺血期间，高能磷酸盐成分降解等Prine代谢显着增加，神经元细胞中产生自由基。2）年龄相关脑部疾病的分子基础分析：进行PET和MR 1图像之间的配准并建立方法来评估血流和/或葡萄糖代谢的区域。与临床健康犬相比，痴呆犬的脑血流减少，葡萄糖代谢也减少，尤其是皮质。在组织病理学检查中，几乎所有动物包括野生动物都有老年斑和血管周围淀粉样蛋白沉积，与老年人相似，这些组织病理学检查结果与年龄的增长有明显的相关性。此外，还评估了视觉诱发电位（VEP）。老年Beagle犬P2潜伏期随年龄的增长而延长，VEP可作为老年性脑病的诊断工具。3）老年性脑病动物模型：采用脑内注射氯化铁的方法建立大鼠反复自发性癫痫模型。所有大鼠在治疗后4个月均出现癫痫发作。脑中天冬氨酸、谷氨酸、牛磺酸和GABA的浓度降低，但这些物质的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.