The effect of resveratrol on oligodendrocyte ion channels in an ischemic myelin injury model induced by oxygen-glucose deprivation

ABSTRACT The Effect of Resveratrol on Oligodendrocyte Ion Channels in an Ischemic Myelin Injury Model Induced by Oxygen-Glucose Deprivation Objective: Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by myelin loss in the central nervous system, in which oligodendrocyte ion channel dysfunction plays a key pathogenic role. This study investigated the effects of resveratrol on Kir4.1, TRPM4, and TRPA1 ion channels in an oxygen–glucose deprivation (OGD)-induced ischemic myelin injury model. Materials and Methods: Acute brain slices (225 µm thick) obtained from 10–17-day-old BALB/c mice were divided into four groups: Control, Resveratrol (50 µM), Ischemia (OGD), and Resveratrol+Ischemia. Oligodendrocytes were identified by Olig2 immunofluorescence staining. Patch-clamp recordings were performed using the whole-cell voltage-clamp configuration. TRPA1, Kir4.1, and TRPM4 current components were isolated by the subtraction method following administration of polygodial, BaCl₂, and 9-phenanthrol, respectively. Protein expression levels of Olig2, Kir4.1, TRPM4, BCL-2, BAX, and Caspase-3 were evaluated by Western blot analysis. Results: Kir4.1 and TRPM4 current components were markedly suppressed in the ischemia group. Although current amplitudes remained reduced in the Resveratrol+Ischemia group, pharmacological modulation of ion channels was significantly preserved compared with the ischemia group (p<0.05). Western blot analysis showed reduced TRPM4 and Olig2 expression levels in the Resveratrol+Ischemia group (p<0.05), whereas no significant differences were detected in Kir4.1, BCL-2, BAX, or Caspase-3 expression levels (p>0.05). Conclusion: In acute ischemic myelin injury, the loss of Kir4.1 function appears to be largely associated with reversible post-translational mechanisms, whereas TRPM4 is reduced at both functional and protein levels. Resveratrol demonstrated neuroprotective potential by preserving the electrophysiological responsiveness of these ion channels. These findings may contribute to the development of novel neuroprotective strategies for multiple sclerosis. Keywords: İschemic myelin injury, Kir4.1, Multiple sclerosis, Oligodendrocyte, Resveratrol, TRPM4