Intranasal nerve growth factor enhances striatal neurogenesis in adult rats with focal cerebral ischemia

Abstract

Nerve growth factor (NGF) has been proved with the potential of promoting neurogenesis in adult mammalians. This study was aimed to investigate the effect of intranasal (IN) NGF on striatal neurogenesis and functional recovery in adult rats with focal cerebral ischemia. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h, and then reperfused. NGF or vehicle was intranasally administered 24 h after cerebral reperfusion, and the treatments continued for 6 consecutive days there after. All animals were injected with 5-bromodeoxyuridine (BrdU) twice daily for 5-7 days after MCAO, and sacrificed 1 day and 28 days, respectively, after the last BrdU injection. Neural cell proliferation and survival in different brain regions were analyzed. Functional tests and immunohistochemical staining were also performed. The results showed that treatment with IN NGF failed to increase cell proliferation but improved survival of newly generated cells in ipsilateral striatum and subventricular zones (SVZ). Double immunofluorescence with BrdU and neuronal nuclei protein, a mature neuronal marker, were increased in striatum and SVZ in rats treated with IN NGF. The functional recovery was also observed at time of neurogenesis enhancement in striate. In conclusion, IN NGF may enhance neurogenesis and survival of newly generated cells, which may result in improved functional recovery after cerebral ischemia.