Correlation between fibroblast growth factor expression and cell proliferation in experimental brain infarct: studied with proliferating cell nuclear antigen immunohistochemistry.
Astrogliosis, angiogenesis and macrophage activity are classical responses of brain to injury. The factors that induce these changes and the dynamic interaction among cells in the environs of the injured brain remain unclear. In the present rat brain infarct model, we studied the spatiotemporal relationship between basic fibroblast growth factor (bFGF) expression and cell proliferation using proliferating cell nuclear antigen (PCNA) as an S-phase marker. We demonstrated an early astrocytic and neuronal activation with enhanced expression of bFGF in areas adjacent to the infarct. This was followed by a period from 3-5 days of intense cell proliferation. Proliferating cell nuclear antigen-labeled nuclei were demonstrated in perineuronal satellite cells, endothelial cells, vascular pericytes, macrophages and glial cells. These cells appeared to respond to the same mitogen(s) and they produced bFGF during the proliferative phase. There was a simultaneous spreading of neuronal activation and glial proliferation from the infarct to the entire ipsilateral hemisphere and through the coronal radiations to the contralateral hemisphere. This spreading follows the pattern of spreading of edema fluid. Our findings suggest that cell proliferation in the brain infarct may be induced by bFGF released by neurons and sustained by bFGF and other growth factors produced by non-neural cells on an autocrine basis.
Liu
H M
HM
Department of Pathology, National Cheng Kung University, Medical College, Tainan, Taiwan, Republic of China.
Chen
H H
HH
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002544:Cerebral Infarction / Q000378:metabolism* / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000096:biosynthesis*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen; D051381:Rats; D017207:Rats, Sprague-Dawley; D016196:S Phase; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D016222:Fibroblast Growth Factor 2