Kainate-induced brain lesion: similar local and remote histopathological and molecular changes as in ischemic brain infarct.
Cerebral ischemia/hypoxia induces histopathological changes characterized by nuclear and cytoplasmic condensation and sustained c-fos expression. The ischemic changes are thought to be initiated by excessive glutamate released by the ischemic neurons. However, no comparative study has been made between the pathological and molecular changes caused by local injection of excitotoxin and by ischemia. In the present study, we investigated the histopathological changes in rat brains induced by an intracerebral microinjection of kainic acid, a potent analogue of glutamate using two newly available markers for ischemic neurons: Fos immunohistochemistry and EA 50 stain. The rats were sacrificed at intervals from 1 hour (h) to 28 days. We demonstrated that the neurons at the site of injection developed changes typical of ischemia 1 h post-lesion: nuclear and cytoplasmic condensation, strong Fos immunoreactivity and positive EA 50 stain. By 1 day, the neurons underwent necrosis and an infarct-like picture was produced. The neuronal degeneration rapidly spread to the bilateral neocortex, CA3 and CA4 regions of hippocampus, piriform gyrus, amygdala and cerebellar Purkinje cells. After 3 days, there was neovascularization and macrophage production in the lesion center and astrocytic proliferation at the lesion periphery. The CA1 of hippocampus showed delayed neuronal necrosis typical of ischemia. Thus, intracerebral microinjection of KA induces similar histopathological and molecular changes as those occurring in brain infarct and is a simple and reliable model for studying changes related to focal brain infarct.
Liu
H M
HM
Department of Neurobiology, Hunan Medical University, Changsha, China.
Lei
D L
DL
Yang
D L
DL
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001927:Brain Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology*; D007608:Kainic Acid; D008297:Male; D008845:Microinjections; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D013997:Time Factors
D016760:Proto-Oncogene Proteins c-fos; D007608:Kainic Acid