Resveratrol ameliorates autophagic flux to promote functional recovery in rats after spinal cord injury

Abstract

Resveratrol is known to improve functional recovery after spinal cord injury, but the exact mechanism involved is yet unclear. The aim of this study was to clarify whether resveratrol can exert neuroprotective effects via activating neuronal autophagic flux, in view of the underlying role of the autophagic flux mediated by resveratrol on neuronal apoptosis after spinal cord injury, and identify the role of the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/ p70 ribosomal protein S6 kinase (p70s6k) signal pathway in the autophagic flux mediated by resveratrol. The results obtained strongly indicate that resveratrol improved functional recovery in Sprague–Dawley rats after acute spinal cord injury, preserved their motor neurons, alleviated the neuronal apoptosis, and ameliorated neuronal autophagic flux. After blocking the autophagic flux, the neuroprotective effects of resveratrol were eliminated. Furthermore, it was proved that resveratrol can activate the LKB1/AMPK/mTOR/p70s6k pathway in vivo and in vitro, and the LKB1/AMPK/mTOR/p70s6k pathway plays a vital role in activating the autophagic flux mediated by resveratrol in PC12 cells. Thus, resveratrol enables to ameliorate neuronal autophagic flux via the LKB1/AMPK/mTOR/p70s6k pathway to alleviate apoptosis, and finally ameliorating functional recovery after acute SCI in SD rats.