Administration Of Sonic Hedgehog Protein Produces The Therapeutic Effects In Stroke Damage

Objective:Here, we investigated the clinical implications of Shh protein in ischemic stroke and explored the underlying molecular basis.Methods:Human recombinant Shh protein (rHu Shh) or PBS was injected into cerebral ventricle immediately after middle cerebral artery occlusion (MCAO) surgery. For evaluating its role on cerebral recovery within 24 hrs, we examined the neurological deficits, blood-brain barrier (BBB) permeability, cerebral edema, infarct volume and cerebral blood flow (CBF) at day 1 after MCAO. For testing its underline mechanism of protective effect, microvascular density was measured at day 1,3 and 7. The proliferation and survivation of microvascular endothelial cells were detected in vivo and in vitro. The expression of Shh downstream genes and angiogenetic factors were determined at protein and/or mRNA levels.Results:We found that 1) Shh alleviated MCAO-induced brain damage, cerebral edema, BBB destruction and preserved the CBF, which were associated with Patched1 and Gli-1 up-regulation.2) Shh improved the microvascular density in peri-infarct area, enhanced the proliferation of microvascular endothelial cells and protect the microvascular endothelial cells subjected to the oxygen-glucose deprivation (OGD).3) Shh increased the angiogenesis in peri-infarct area at later days following MCAO, which was accompanied with up-regulation of Ang-1 and VEGF expression.Conclusions:These data demonstrate that brain administration of Shh protein could protect brain from ischemic injury and promote angiogenic repair.