Studies on molecular and pathophysiological mechanisms in age related brain disease

对年龄相关性脑疾病的分子和病​​理生理机制进行了两年（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，特别是羟基自由基，通过钙内流和细胞膜电压依赖性钙离子通道紊乱与神经细胞死亡密切相关。缺血状态下，高能磷酸盐成分的降解等碱代谢显着增加，神经元细胞中产生自由基。2）年龄相关性脑疾病的分子基础分析：进行PET和MR1图像之间的配准，并建立了用于评估血流和/或葡萄糖代谢区域的方法。与临床健康的狗相比，痴呆症狗的大脑（尤其是皮质）的血流量和葡萄糖代谢均减少。在组织病理学结果中，几乎所有动物（包括野生动物）都显示出老年斑和淀粉样蛋白的血管周围沉积物，就像老年人的情况一样。这些组织病理学结果明显与高龄相关。此外，还评估了视觉诱发电位（VEP）。老年Beagle犬随着年龄的增长，P2潜伏期（峰2）延长，VEP被认为是诊断老年脑疾病的可用工具。3）老年脑疾病的动物模型：尝试对大鼠颅内注射氯化铁，建立复发性自发性癫痫模型。所有注射的大鼠在治疗后 4 个月均出现癫痫发作。大脑中天冬氨酸、谷氨酸、牛磺酸和 GABA 的浓度降低，但这些物质的病理生理学影响尚未完全阐明。

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.