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Resveratrol Pretreatment Decreases Ischemic Injury and Improves Neurological Function Via Sonic Hedgehog Signaling After Stroke in Rats

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Abstract

Resveratrol has neuroprotective effects for ischemic cerebral stroke. However, its neuroprotective mechanism for stroke is less well understood. Beneficial actions of the activated Sonic hedgehog (Shh) signaling pathway in stroke, such as improving neurological function, promoting neurogenesis, anti-oxidative, anti-apoptotic, and pro-angiogenic effects, have been noted, but relatively little is known about the role of Shh signaling in resveratrol-reduced cerebral ischemic injury after stroke. The present study tests whether the Shh pathway mediates resveratrol to decrease cerebral ischemic injury and improve neurological function after stroke. We observed that resveratrol pretreatment significantly improved neurological function, decreased infarct volume, enhanced vitality, and reduced apoptosis of neurons in vivo and vitro after stroke. Meanwhile, expression levels of Shh, Ptc-1, Smo, and Gli-1 mRNAs were significantly upregulated and Gli-1 was relocated to the nucleus. Intriguingly, in vivo and in vitro inhibition of the Shh signaling pathway with cyclopamine, a Smo inhibitor, completely reversed the above effects of resveratrol. These results suggest that decreased cerebral ischemic injury and improved neurological function by resveratrol may be mediated by the Shh signaling pathway.

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Acknowledgments

This work was supported by grants from the National Nature Science Foundation of China (grant no. 81071119) and the National Key Clinical Specialties Construction Program of China for Neurology (The First Affiliated Hospital of Chongqing Medical University No. [2014]27).

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    Authors and Affiliations

    1. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, 400016, Chongqing, China

      Pingping Yu, Li Wang, Fanren Tang, Li Zeng, Luling Zhou, Xiaosong Song, Wei Jia, Jixiang Chen & Qin Yang

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    1. Pingping Yu
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    Pingping Yu and Li Wang contributed equally to this work and they are co-first authors.

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    Yu, P., Wang, L., Tang, F. et al. Resveratrol Pretreatment Decreases Ischemic Injury and Improves Neurological Function Via Sonic Hedgehog Signaling After Stroke in Rats. Mol Neurobiol 54, 212–226 (2017). https://doi.org/10.1007/s12035-015-9639-7

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