EXPERIMENTAL BRAIN INJURY INDUCES EXPRESSION OF AMYLOID PRECURSOR PROTEIN, WHICH MAY BE RELATED TO NEURONAL LOSS IN THE HIPPOCAMPUS

Previous reports have demonstrated that some focal brain injuries incr ease amyloid precursor protein (APP) immunoreactivity in the region su rrounding the injury where it was localized, in damaged axons and in p re-alpha 2 cells of the entorhinal cortex. However, to date, APP expes sion in the hippocampus remote from the impact site has not been compr ehensively studied. Therefore, we have evaluated APP expression not on ly in the locally injured cerebral cortex but also in the hippocampus remote from the impact site, In the present paper, diffuse axonal inju ry was induced in rats in midline fluid percussion injury, APE express ion was examined post injury using Western blot analysis and immunohis tochemistry. Western blot analysis demonstrated that the expression of 100-kd APP was increased in both the cerebral cortex and hippocampus 24 h after injury. It then decreased in the hippocampus, but did not c hange in the cerebral cortex, 7 days after injury, Immunohistochemical studies showed increased immunoreactivity of APP in the neuronal peri karya and reactive astrocytes near the region of injury in the cerebra l cortex 24 h to 7 days after injury, In the hippocampus, APP accumula ted in the CA3 neurons 24 h and 3 days after injury, although no hemor rhagic lesions were seen at that site, The APP positive neurons in CA3 showed shrunken cell bodies and pyknotic nuclei 3 days after injury, and some of the neurons in CA3 had disappeared by 7 days postinjury, T he results of present study suggest that traumatic brain injury induce s overexpression and accumulation of APP in neuronal perikarya and tha t these events are followed by degeneration of CA3 neurons, Further, t he decline in APP expression in the hippocampus is thought to be due t o neuronal loss in CA3 subsector.