Valproic acid ameliorates morpho-dysfunctional effects triggered by Ischiatic nerve crush injury-induced by compression model in mice: Nerve regeneration and immune-modulatory pathway

Abstract

Peripheral nerve injuries are extremely severe and may lead to permanent disability, despite the regenerative capacity of the peripheral nervous system (PNS). To date, there is no established pharmacological therapy capable of predicting functional recovery and alleviation of trauma-related symptoms such as neuropathic pain, inflammation and weakness, which are the main targets for current therapies. In this work we provide new evidence for a therapeutic use of valproic acid (VPA) upon ischiatic nerve injury. Ischiatic nerve-injured mice treated with VPA after lesion, displayed an improvement in pain and motor function associated with an increase in the number of myelinated nerve fibers, and exhibited a more organized microenvironment during regeneration. In addition, VPA treatment also promoted an immunomodulatory capacity, leading to a significant enhancement of neutrophils in the peritoneal cavity, suggesting its role on the sensory and motor recovery after ischiatic nerve injury. This highlights the physiological role of VPA during ischiatic nerve regeneration and contributes to the characterization of innovative pharmacological epigenetic therapy capable of accelerating peripheral nerve regeneration with critical impacts on the clinical practice.

Keywords

• Ischiatic nerve
• Crush injury
• Valproic acid
• Neutrophils