Studies on molecular and pathophysiological mechanisms in age related brain disease

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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.