NGF/FAK signal pathway is implicated in angiogenesis after acute cerebral ischemia in rats. (13th April 2018) - Zhao, Haiting
Highlights: Angiogenesis was formed and increased by NGF-pretreatment post-acute cerebral ischemia. The effects of angiogenesis by NGF was significantly reduced by FAK inhibitor TAE226. The CD31 and α-SMA expression were significantly increased by NGF and were markedly reduced by TAE226 in Matrigel model. The P-FAK protein was markedly increased by NGF and decreased by TAE226. The number of BrdU-positive cells was significantly increased by NGF and was significantly reduced by TAE226 in the SVZ and SVG of cerebral ischemia. Abstract: Neurogenesis in the cerebral infarction after an ischemic event is important to the rehabilitation of patients. However, the mechanism of angiogenesis around cerebral ischemia is not clear. Our study designed to test whether the nerve growth factor (NGF)-P-focal adhesion kinase (FAK) signaling pathway for associations with angiogenesis plays a key role in post-acute cerebral ischemia of rats. Firstly, we implanted the Matrigel, a carrier of basement membrane matrix, into the abdominal skin of rats to identify the relevant components of the NGF-P-FAK signaling pathway related to angiogenesis. Secondly, we used a model established by ligation of the middle cerebral artery (MCA) to observe the effect of the same signal pathway on angiogenesis in the subventricular and subgranular zones of the dentate gyrus(SVG and SGZ). The results showed that the tissue scores was significantly increased by NGF. However, the tissue scores was signifcaintly decreased by FAK inhibitor TAE226. Furthermore, CD31 and α-SMA were significantly increased by NGF and were decreased by anti-NGF and TAE226 in Matrigel. The P-FAK protein expression in Matrigel was markedly increased by NGF and decreased by TAE226. In the SVZ and SVG of cerebral ischemia, the numbers of BrdU-positive cells were significantly increased by NGF and decreased by TAE226, respectively. Our findings suggest that the therapy targeting the NGF-P-FAK signaling pathway may be an option for patients suffering from cerebral ischemia.