Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury.

Zhuofeng Ding,Xin Yang,Qulian Guo,Wen Zhou,Jiawei Cao,Changsheng Huang,Yu Zou,Yu Shen

doi:10.3389/fnins.2018.00341

Zhuofeng Ding, Xin Yang + Show 6 more

Open Access

https://doi.org/10.3389/fnins.2018.00341

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Abstract

Peripheral nerve injuries are generally associated with incomplete restoration of motor function. The slow rate of nerve regeneration after injury may account for this. Although many benefits of resveratrol have been shown in the nervous system, it is not clear whether resveratrol could promote fast nerve regeneration and motor repair after peripheral nerve injury. This study showed that the motor deficits caused by sciatic nerve crush injury were alleviated by daily systematic resveratrol treatment within 10 days. Resveratrol increased the number of axons in the distal part of the injured nerve, indicating enhanced nerve regeneration. In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. Inactivation of p300 acetyltransferase reversed the resveratrol-induced expression of VEGFs and motor repair in rats that had undergone sciatic nerve crush injury. The above results indicated that daily systematic resveratrol treatment promoted nerve regeneration and led to rapid motor repair. Resveratrol activated p300 acetyltransferase-mediated VEGF signaling in the affected ventral spinal cord, which may have thus contributed to the acceleration of nerve regeneration and motor repair.

Highlights

Peripheral nerve injuries represent a significant source of patient morbidity and disability (Asplund et al, 2009; Kawamura et al, 2010)
Rats that had received sciatic nerve crush injury did not show any reduction in body weight when compared with the sham-operated rats (Figure 1A), indicating that the treatment is not likely to cause toxicity (Johnson et al, 2011)
sciatic function index (SFI) was the most sensitive to reflect the alleviation of motor deficit, as the increase of SFI was observed as early as 3 days after the treatment, much earlier than the increase of the other two parameters

Summary

Introduction

Peripheral nerve injuries represent a significant source of patient morbidity and disability (Asplund et al, 2009; Kawamura et al, 2010). The prevalent hypothesis for this is that the injury-induced increase in axonal growth is too slow and that, by the time axons reach distal denervated nerves, the milieu has become nonpermissive for growth (Sulaiman and Gordon, 2000; Gordon et al, 2011) This long delay for axons to reach their targets is thought to prevent functional restoration (Sakuma et al, 2016). The treatment of VEGFa or VEGFb induced extensive neurite growth and mediated nerve repair (Mackenzie and Ruhrberg, 2012; Guaiquil et al, 2014). VEGFa and VEGFb, by signaling via their receptors, have direct effects in neuron cell bodies and promote axon elongation and nerve regeneration after peripheral nerve injury (Carmeliet and Storkebaum, 2002; Guaiquil et al, 2014)

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Conclusion