c-fos protein expression and ischemic changes in neurons vulnerable to ischemia/hypoxia, correlated with basic fibroblast growth factor immunoreactivity.
Injuries to the brain induce rapid expression of c-fos and c-jun proto-oncogenes in neurons. The protein products (Fos and Jun) of these cellular immediate early genes are thought to regulate target genes that participate in fundamental biological responses. In recent studies of rat brain infarct we demonstrated that gliosis and angiogenesis, two of the fundamental biological responses, are related to neuronal expression of basic fibroblast growth factor (bFGF). In the present study, we explore the linkage between c-fos and bFGF genes by comparing the temporal and spatial domains of Fos and bFGF immunoreactivities (IR) in brain infarct and in transient global ischemia. We demonstrate colocalization of Fos-IR and ischemic changes in neurons at infarct periphery and in regions of "selective vulnerability" beginning 3 hours post-infarction and lasting up to 1-2 weeks. These are: cortical neurons in layers II-III and V, interneurons in hippocampal formation, cerebellar Purkinje cells, and many subcortical nuclei and brainstem nuclei. bFGF-IR appears 12-24 hours later than Fos-IR in the same region but in non-ischemic neurons and the expression persists beyond 2 weeks. Persistent and not transient c-fos expression appears to be associated with ischemic neuronal death, although some of these neurons may survive beyond 2 weeks postinfarction.
Department of Pathology, National Cheng Kung University, Medical College, Tainan, Taiwan, R.O.C.
H M
HM
Liu
H H
HH
Chen
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis*; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016760:Proto-Oncogene Proteins c-fos; D016222:Fibroblast Growth Factor 2