Decanoic acid mitigates ischemia reperfusion injury by modulating neuroprotective, inflammatory and oxidative pathways in middle cerebral artery occlusion model of stroke in rats

Abstract

Objective: Amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) is an ionotropic transmembrane receptor for glutamate. AMPA receptor blockers have been reported to prevent neurological damage and enhance the post stroke recovery in rats. Decanoic acid, a medium-chain fatty acid, has been reported to exhibit non-competitive AMPA receptor antagonism. This study evaluated the effect of decanoic acid administered before and after ischemia reperfusion injury on neurological damage and post stroke recovery in rats. Methods: Middle cerebral artery occlusion (MCAo) was performed by using the intraluminal method to induce focal cerebral ischemia. Decanoic acid (120 mg/kg) was administered orally for 1 day (5-10 min post reperfusion) in one group and for 2 days (24 h pre and 5-10 min post reperfusion) in the other group. Effect on neurological damage and post stroke recovery was assessed by neurobehavioral parameters, MRI and TTC staining along with inflammatory, oxidative, apoptotic, and neuroprotective biomarkers. Results: Decanoic acid significantly reduced the MCAo induced neurological damage and infarct size. Decanoic acid treatment increased the motor coordination and grip strength. Furthermore, levels of inflammatory (TNFα, IL-1β and IL-6), oxidative stress (MDA), apoptotic (TUNEL positive cells) and neurological injury (GFAP) biomarkers were reduced after decanoic acid treatment. Anti-inflammatory cytokine (IL-10) and neuroprotective markers (NT-3, BDNF and TrkB) were found to be significantly increased with decanoic acid treatment. Conclusion: This study showed protective effects of decanoic acid against ischemia reperfusion injury in rats. Anti-inflammatory, antioxidant, neuroprotective, and anti-apoptotic properties may be responsible for the beneficial effects of decanoic acid observed in the study.