Abstract / Summary
Epilepsy is a long-term neurological condition marked by neuronal excitotoxicity, oxidative stress, and inflammation of the nervous system. This study seeks to explore the neuroprotective and anti-seizure properties of Resveratrol (RSV) and the molecular processes involved in a pentylenetetrazol (PTZ)-induced kindling epilepsy model, with a focus on ion channels, apoptosis, and SIRT1 pathway. A total of thirty-two Wistar albino rats were assigned into four groups: Sham, RSV, PTZ, and PTZ + RSV. Following kindling induction via PTZ (35 mg/kg, 3 days/week) or equivalent saline administration for control groups, subsequent RSV treatment (5 mg/kg/day, i.p.) or saline was administered for 28 days. Brain tissues were harvested 24 h after the final injection. Epileptic activity was captured through the use of electrocorticography (ECoG), while tissue damage to the hippocampus was evaluated via hematoxylin-eosin (H&E) staining. Molecular levels of SIRT1, Caspase-3, and S100B protein were assessed via immunofluorescence, whereas SERCA2a, CACNA1G, HCN2, Caspase-3, Caspase-9, and SIRT1 gene expression levels were measured through qPCR analysis. RSV treatment greatly extended the initial myoclonic jerk delay ( p = 0.0001) and lowered both the seizure phase and total spike count compared to the PTZ group. Microscopic examination revealed that RSV maintained tissue health by reducing neuronal deterioration and inflammation in the hippocampal CA1 area. Immunofluorescence analysis revealed that RSV treatment restored SIRT1 levels, which were previously diminished by PTZ, and significantly reduced the elevated markers of apoptosis and glial activation. Furthermore, qPCR analysis demonstrated that RSV treatment significantly reversed PTZ-induced gene expression alterations by upregulating the expressions of SERCA2α, CACNA1G, HCN2, and SIRT1 ( p < 0.0001), while downregulating the expressions of Caspase-3 and Caspase-9. RSV exerts significant neuroprotective effects in the PTZ kindling model by modulating the SIRT1-mediated stress response and preventing neuronal apoptosis. Notably, this study provides the first in vivo evidence that RSV modulates SERCA2a, CACNA1G, and HCN2 ion channel gene expressions to control intracellular calcium balance and neuronal excitability during epileptogenesis.