Correlation between proto-oncogene, fibroblast growth factor and adaptive response in brain infarct.

Ischemia/hypoxia rapidly induce ischemic changes in vulnerable neurons: cortical neurons in layers II-III and V, hippocampal neurons, cerebellar Purkinje cells and certain basal ganglia and brainstem neurons. The ischemic changes are manifested histologically by nuclear pyknosis, cytoplasmic shrinkage and basophilia. These neurons exhibit strong and persistent expression of immediate early genes (IEGs): c-fos and c-jun. The onset of IEG expression is followed within a day by enhanced bFGF expression in non-ischemic neurons in the same general regions. The appearance of bFGF is followed within another day by proliferation of blood vessels, macrophages and glial cells around the infarct. The newly-formed blood vessels and macrophages migrate into the necrotic infarct aiming at disposal of the necrotic debris. The gliosis although concentrated around the infarct spreads to involve remote regions of both hemispheres. Based on the spatiotemporal correlation between cell proliferation and bFGF and the known mitogenic properties of bFGF, we believe that this molecule may be responsible for the late response in brain infarct including angiogenesis, gliosis and macrophage proliferation. The physiological roles of IEGs in the chain of adaptive response following brain infarction and its relationship with bFGF are subjects pending future investigations.