Basic fibroblast growth factor stimulates the proliferation and differentiation of neural stem cells in neonatal rats after ischemic brain injury

Abstract

A little is known about the proliferation and fate of neural stem cells in the subventricular zone (SVZ) after cerebral ischemia. However, how endogenous neural stem cells are activated in the premature brain is not clear, although basic fibroblast growth factor (bFGF) is important in neurogenesis. To investigate the effect of bFGF on the proliferation and differentiation of neural stem cells after brain ischemia, we observed cellular changes in the subventricular zone (SVZ) of 3-day-old rats (approximately equivalent to premature infants) using immunofluorescence assays, Western blot analysis, and real-time quantitative PCR methods. The bilateral common carotid artery (BCCA) was occluded in 108 animals, then half received bFGF 10 ng/g. Besides, 54 rats without ischemia as normal control. Proliferating cells were labeled by bromodeoxyuridine (BrdU) through intraperitoneal injection in a pulsed or a cumulative protocol. Rats were killed at 4, 7, and 14 days after ischemic injury. The number of proliferating cells in the SVZ in bFGF-treated rats was higher than that in untreated rats; bFGF also promoted neural stem cell differentiation into neurons, astrocytes, and oligodendrocytes. Western blot analysis and real-time quantitative PCR assays confirmed these results. We suggest that bFGF promotes the repair of ischemia brain injury through increasing the proliferation of neural stem cells and their differentiation into neurons, astrocytes, and oligodendrocytes.