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 respo nses 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 (b FGF) expression and cell proliferation using proliferating cell nuclea r antigen (PCNA) as an S-phase marker. We demonstrated an early astroc ytic 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-labe led nuclei were demonstrated in perineuronal satellite cells, endothel ial cells, vascular pericytes, macrophages and glial cells. These cell s appeared to respond to the same mitogen(s) and they produced bFGF du ring the proliferative phase. There was a simultaneous spreading of ne uronal activation and glial proliferation from the infarct to the enti re ipsilateral hemisphere and through the coronal radiations to the co ntralateral hemisphere. This spreading follows the pattern of spreadin g 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 a utocrine basis.