The Overexpression of Sonic Hedgehog Associates with Collateral Development and Amelioration of Oxidative Stress in Stroke Patients

Abstract

PurposeSonic hedgehog (SHH) signaling pathway in oxidative stress condition has been acknowledged as a key trigger for angiogenesis and collateral vessel growth in the ischemic brain, and it exerts a protective effect on neuronal cells during oxidative stress. MethodsA total of sixty patients (n = 30 good collateral profile and n = 30 poor collateral profile) diagnosed with acute cerebral ischemia were enrolled in this study. qRT-PCR was performed to analyze the expression levels of SHH, Gli1, and superoxide dismutase (SOD), genes. Also, the serum levels of oxidative stress markers were determined in experimental groups. ResultsThe expression levels of SHH and Gli1 genes were significantly (p < 0.05) higher in stroke patients with good collateral circulation compared with those with poor collateral circulation, while SOD gene expression was similar between two groups (p > 0.05). A significantly positive correlation was found between the gene expression of SHH and Gli1 (r = 0.604, p < 0.001), SOD and Gli1 (r = 0.372, p < 0.003) genes. Our findings showed that the serum level of total antioxidant capacity (TAC) and Glutathione (GSH) and SOD enzyme activity was significantly (p < 0.05) increased, while serum total oxidant status (TOS) and malondialdehyde (MDA) levels were significantly (p < 0.05) decreased in patients with good collateral circulation as compared with those with poor collateral circulation. ConclusionOur observations shed light on the association of the SHH/Gli1 signaling pathway with cerebral collateral vessel development following ischemia. Oxidative stress in stroke patients with poor collateral circulation may result in the overexpression of SHH/Gli1 signaling pathway which possibly contribute to oxidative stress attenuation, as well as modulate angiogenesis and collateral vessels development.