Acidic fibroblast growth factor delivered intranasally induces neurogenesis and angiogenesis in rats after ischemic stroke.

BACKGROUND

Enhancing angiogenesis and neurogenesis is a novel therapeutic strategy for stroke treatment. Acidic fibroblast growth factor (aFGF) has been shown to have both angiogenesis and neurogenesis effects in animals with cerebral ischemia. But aFGF can not enter the brain freely after system administration due to the filtration of the blood-brain barrier (BBB). Intranasal administration of aFGF as a noninvasive method can bypass the BBB and enter the central nervous system directly without systemic adverse effects.

METHODS

To investigate the therapeutic effects of intranasally delivered aFGF, adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and intranasally administrated with aFGF or saline starting at 24 hours and once daily for the subsequent 6 days. BrdU (50 mg/kg) was intraperitoneally injected daily for 13 days. A modified neurological severity scores test was performed before and at 1, 7, 14 days after MCAO. Infarct volumes were evaluated after hematoxylin and eosin staining. Immunohistochemistry was performed to detect BrdU immunoreactive cells and BrdU / DCX double labeled cells. Microvessels were labeled by FITC-dextran and the numbers, length and diameters of vessels were also measured.

RESULTS

Intranasal aFGF did not significantly reduce the lesion size, but did improve neurological functional recovery. In the subventricular zone and the striatum, numbers of BrdU immunoreactive cells were significantly increased in aFGF group at day 14, and the majority of BrdU positive cells were co-labeled with DCX. At 14 days after ischemia, the percentage of BrdU positive endothelial cells around the ischemic lesions were significantly increased in aFGF group, compared with control. Quantitative analysis of FITC-dextran perfusing vessels revealed a significant increase of vessels in the boundary regions of ischemia in the rats treated with aFGF. But there were no significant differences concerning the length and the diameter of the vessels between groups.

CONCLUSION

In summary, aFGF may enhance neurogenesis and angiogenesis after focal cerebral ischemia. Intranasal administration of aFGF may be a feasible approach for ischemic stroke treatment.