Effects Of The Sonic Hedgehog Signaling Pathway On Neovascularization In Rats With Cerebral Ischemia

Objective: To explore the effect of the activated sonic hedgehog signaling(SHH) pathway on neovascularization in rats with cerebral ischemia.Methods: The model of middle cerebral artery occlusion(MCAO) in rats was induced by nylon suture embolisation.All the rats were randomly divided into four groups: Sham operation group, MCAO+PBS group, MCAO + SHH( SHH signaling pathway agonist) group, and MCAO + SHH + CYC( SHH signaling pathway antagonist) group. Three days or seven days later, the neurological deficits were assessed by Longa standard, the infarct volume were acquired using the AIS imaging research software, the cerebral blood flow( CBF) were measured with laser Doppler flowmeter, the total blood vessel length on the surface of left brain hemisphere was conducted by using AIS imaging research software, the levels of v WF were measured by immunohistochemistry. The expressions of neovascularization factors( VEGF and Ang-1) were detected by RT-PCR and western blot.Results: Compared with MCAO+PBS group on day 3 and day 7, the level of neurological deficits and infarct volume in MCAO+SHH group were obviously decreased, the level of CBF, total blood vessel length and expression of v WF, VEGF and Ang-1 were significantly increased. After blocked with CYC, the level of neurological deficits and infarct volume were obviously increased, the level of CBF, total blood vessel length and expression of v WF, VEGF and Ang-1 were decreased significantly.Conclusion: Activation of SHH pathway can improve neurological functional recovery, increase the cerebral blood flow and promote neovasculation after MCAO. VEGF and Ang-1 may be the downstream molecules of SHH pathway and play a key role in neovasculation. Our results suggest a potential role of SHH signaling pathway in neovascularization after stroke.