Protective effect of valproic acid on ischemia-reperfusion induced spinal cord injury in a rat model

J Spinal Cord Med. 2024 Sep;47(5):775-782. doi: 10.1080/10790268.2023.2257854. Epub 2023 Nov 17.

Abstract

Purpose: This study aims to determine the anti-inflammatory, antioxidant, and anti-apoptotic effects of valproic acid (VPA) on rat spinal cord tissue in ischemia-reperfusion (IR) injury model created by abdominal aorta occlusion.

Materials and methods: Sprague Dawley rat (male sex) weighing 190-260 g divided into four experimental groups: control only underwent laparotomy, sham group, pre-IR injury (200 mg/kg dose), and post-IR injury (300 mg/kg) VPA. We measured serum levels of TNF-α, IL-6, IL-1β, IL-18, Total Oxidant Status (TOS) and Total Antioxidant Status (TAS), and serum Oxidative Stress Index (OSI) ratio, and tissue expression of Bax and Bcl2, Caspase3, and Bax/Bcl2 ratio.

Results: Serum IL-18 was higher in the sham than the control group(P = 0.001), and there were declines in the pre-IR treatment (P = 0.002) and the post-IR treatment when compared to sham (P = 0.001). Despite these reductions, IL-18 expression levels in both the pre- and post-IR treatment groups were higher than in the control group (P = 0.001 & P = 0.003). The favorable effects of pre-IR VPA administration on immunohistochemical biomarkers were superior to post-IR VPA administration.

Conclusions: Comparative analyses between prophylactic VPA administration and post-IR interventions revealed congruence in their anti-inflammatory and anti-apoptotic ramifications. VPA can reduce spinal cord IR injury in an aortic occlusion model of rats.

Keywords: Inflammation; Ischemia-reperfusion injury; Spinal cord; Valproic acid.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Disease Models, Animal
  • Male
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley*
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / prevention & control
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord Injuries* / complications
  • Spinal Cord Injuries* / drug therapy
  • Spinal Cord Injuries* / metabolism
  • Spinal Cord Injuries* / pathology
  • Valproic Acid* / pharmacology
  • Valproic Acid* / therapeutic use

Substances

  • Valproic Acid
  • Neuroprotective Agents
  • Antioxidants