Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, PR China; The First Hospital of Dalian Medical University, Dalian 116021, PR China.
Neurosci Lett. 2013 Sep 27;552:81-6. doi: 10.1016/j.neulet.2013.07.042. Epub 2013 Aug 7.
Previous studies have demonstrated that the sonic hedgehog (Shh) pathway plays a neuro-protective role. However, whether the Shh pathway is induced by subarachnoid hemorrhage (SAH) has not been investigated. We sought to investigate Shh activation in the cortex in the early stage of SAH, and assessed the effect of cyclopamine (a specific inhibitor of the Shh pathway) on Shh pathway regulation and evaluated the impact of cyclopamine on SAH. We found that the Shh pathway was up-regulated in the cortex after SAH, and that blocking the Shh pathway increased cell apoptosis. Early brain damages, including brain edema, blood-brain barrier impairment, and cortical apoptosis were significantly aggravated following with cyclopamine treatment compared with vehicle treatment. Our results suggest that the Shh pathway should be activated in the brain after SAH, and plays a beneficial role in SAH development, possibly by inhibiting cerebral oxidative stress through induction of antioxidant and detoxifying enzymes.
先前的研究表明,声波刺猬(Shh)信号通路发挥着神经保护作用。然而,蛛网膜下腔出血(SAH)是否会诱导 Shh 信号通路尚不清楚。我们旨在研究 SAH 早期皮层中 Shh 信号通路的激活情况,并评估沙蟾毒精(Shh 信号通路的特异性抑制剂)对 Shh 信号通路调节的影响,以及评估沙蟾毒精对 SAH 的影响。我们发现,SAH 后皮层中 Shh 信号通路上调,阻断 Shh 信号通路会增加细胞凋亡。与对照组相比,沙蟾毒精处理后,早期脑损伤包括脑水肿、血脑屏障损伤和皮层细胞凋亡明显加重。我们的结果表明,SAH 后大脑中 Shh 信号通路应该被激活,并且在 SAH 发展中发挥有益作用,可能通过诱导抗氧化和解毒酶来抑制脑氧化应激。