Intranasal bFGF-induced progenitor cell proliferation and neuroprotection after transient focal cerebral ischemia

Abstract

Basic fibroblast growth factor (bFGF) is a neurotrophic and vasoactive factor, and has therapeutic potential for some central nervous system (CNS) disorders. In this study, we used the intranasal pathway to administer bFGF in adult rats, and evaluated its neuroprotective benefits and effects on endogenous neural stem cells. The bFGF levels after intranasal administration in normal rats were determined by western blot. Transient focal ischemia was achieved by occlusion of the right middle cerebral artery for 2 h. bFGF was given intranasally 2 h after reperfusion and daily thereafter on 3 successive days. Dividing progenitor cells were labeled with bromodeoxyuridine (BrdU) on day 3 of reperfusion. Rats were killed the next day after BrdU labeling. bFGF levels were significantly raised in the olfactory bulb (OB) and striatum following intranasal administration. Intranasal bFGF treatment improved neurological function and reduced infarct volume after cerebral ischemia/reperfusion, while no influence was observed on the blood pressure. And the BrdU incorporation was enhanced in the ipsilateral subventricular zone (SVZ) and striatum following intranasal administration of bFGF. These results demonstrated that bFGF can be directly delivered into brain following intranasal administration, and protects against cerebral ischemia/reperfusion. The protective effects may be attributed to the reduction of infarct volume and enhancement of endogenous progenitors in brain. Therefore, intranasal administration of bFGF may provide an alternative treatment for brain ischemia and some other CNS disorders.