Resveratrol regulates the recovery of rat sciatic nerve crush injury by promoting the autophagy of Schwann cells

Resveratrol has the ability to promote functional recovery after sciatic nerve crush injury (SNCI), though the mechanism through which this occurs in not fully understood. Resveratrol can promote autophagy, a key process in Wallerian degeneration; thus, we hypothesized that resveratrol could promote recovery from SNCI by promoting Schwann cell autophagy and acceleration of Wallerian degeneration. Motor function recovery was assessed by calculating Sciatic Function Indexes (SFIs) at days 7, 14, 21, 28 post SNCI. Autophagy and myelin clearance were assessed by microtubule-associated protein light chain 3B (LC3B) and myelin protein zero (MPZ) immunofluorescence and Western blot analysis on the fourth day after SNCI. The autophagy of Schwann cells following resveratrol administration was quantified by immunofluorescence in RSC96 cells. Immunofluorescence and Transmission electron microscopy (TEM) were also used in Resveratrol treated sciatic nerve four days post-SNCI to find LC3B positive areas and typical double membrane structures represent for autophagy. The SNCI+resveratrol (crush+Res) groups recovered faster than the SNCI+vehicles (crush+V) group. On day four, almost all of the myelin had regenerated in the crush+Res rats, while the crush+V group's myelin remained intact and the expression levels of LC3-II/I was the highest. On day 28 post-injury, both the control and crush+Res groups' myelin neurofibers reached peak numbers as did the thickness of the myelin sheath. Both in vitro and in vivo immunofluorescence showed that LC3B was colocalized with Schwann cells. This is the first study to observe that resveratrol can promote recovery from SCNI by accelerating the myelin clearance process by promoting autophagy of Schwann cells.