Cerebral ischemia is a common cerebrovascular condition which often induces neuronal apoptosis, leading to brain damage. The sonic hedgehog (Shh) signaling pathway has been reported to be involved in ischemic stroke, but the underlying mechanisms have not been fully elucidated. In the present study, we demonstrated that expressions of Shh, Ptch, and Gli-1 were significantly downregulated at 24 h following oxygen-glucose deprivation (OGD) injury in neurons in vitro, effects which were associated with increasing numbers of apoptotic cells and reactive oxygen species generation. In addition, expressions of synaptic proteins (neuroligin and neurexin) were significantly downregulated at 8 h following OGD, also associated with concomitant neuronal apoptosis. Treatment with purmorphamine, a Shh agonist, increased Gli-1 in the nucleus of neurons and protected against OGD injury, whereas the Shh inhibitor, cyclopamine, produced the opposite effects. Activation of Shh signals promoted CREB and Akt phosphorylation; upregulated the expressions of BDNF, neuroligin, and neurexin; and decreased NF-κB phosphorylation following OGD. Notably, this activation of Shh signals was accompanied by improved neurobehavioral responses along with attenuations in edema and apoptosis at 48 h postischemic insult in rats. Taken together, these results demonstrate that activation of the Shh signaling pathway played a neuroprotective role in response to ischemic exposure via promotion of synaptic and neuronal health.

中文翻译：

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通过促进突触和神经元健康，声波刺猬信号通路在缺血性损伤中的神经保护作用。

脑缺血是一种常见的脑血管疾病，经常诱发神经元凋亡，导致脑损伤。据报道，声波刺猬（Shh）信号通路与缺血性中风有关，但其潜在机制尚未完全阐明。在本研究中，我们证明了在体外神经元中氧葡萄糖剥夺（OGD）损伤后24小时，Shh，Ptch和Gli-1的表达明显下调。与凋亡细胞数量增加和活性氧产生有关的影响。此外，在OGD后8小时，突触蛋白（神经胶蛋白和神经毒素）的表达显着下调，也与神经细胞凋亡相关。用Shh激动剂purmorphamine进行治疗，可增加神经元核中的Gli-1含量，并防止OGD损伤，而Shh抑制剂环巴胺产生相反的作用。Shh信号的激活促进CREB和Akt磷酸化；上调BDNF，神经胶蛋白和神经毒素的表达；和NF- κ减少OGD后B磷酸化。值得注意的是，在大鼠缺血后48小时，Shh信号的这种激活伴随着改善的神经行为反应以及水肿和凋亡的减弱。综上所述，这些结果表明，Shh信号传导途径的激活通过促进突触和神经元健康，对缺血暴露具有神经保护作用。