Vascular growth factors in cerebral ischemia

During the past decade, there has been a surge of interest in growth factors (GFs) that act selectively on vascular endothelium and perivascular cells. Studies employing mutant mice or the administration of recombinant proteins have suggested that these factors not only mediate the proliferation of endothelial cells, but also regulate vascular differentiation, regression, and permeability. During and after cerebral ischemia, brain vasculature becomes leaky and unstable, and the normally impermeable blood-brain barrier breaks down. Several days after the ischemic insult, endothelial cells begin to proliferate, and angiogenesis occurs. Expression studies have shown that key vascular GFs are regulated, during these processes, in a complex and coordinated manner. The distinct pattern of regulation exhibited by each vascular GF suggests a unique role for each factor during the initial vascular destabilization and subsequent angiogenesis that occurs after cerebral ischemia. Data from studies in other biological systems support these suggested roles. Thus, manipulation of vascular GFs may prove to be an effective means of stabilizing or enriching brain vasculature after ischemia, and ameliorating the detrimental effects of blood-brain barrier breakdown and vessel regression after stroke.