Carbamazepine preserves systemic ionic homeostasis and hippocampal Atp1a1 expression following pentylenetetrazol-induced seizures in rats.

Epileptogenesis involves complex neurochemical and neurovascular changes that disrupt the balance between excitatory and inhibitory neurotransmission. Carbamazepine (CBZ) is a standard antiepileptic drug known for blocking voltage-gated sodium channels; however, its potential as a molecular stabilizer of ion transporters such as Na+/K+-ATPase remains largely unexplored. In this study, we investigated the effect of CBZ on systemic ion homeostasis and hippocampal Atp1a1 expression in a rat model of PTZ-induced seizures. The male Wistar rats were divided into three groups (n = 6 per group): control, PTZ (70 mg/kg) and CBZ (50 mg/kg) + PTZ. Serial blood sampling revealed that acute PTZ induced severe systemic imbalances (hypernatremia, hypokalemia, and hypocalcemia). RT-qPCR analysis showed a significant and region-specific downregulation (60%) of mRNA Atp1a1 in the hippocampus, meanwhile in frontal cortex its levels remained stable. Histopathological examination using cresyl violet staining revealed vascular dilation, endothelial disruption, and neuronal pyknosis in the PTZ group. Pretreatment with CBZ effectively prevented systemic ion shifts, preserving hippocampal Atp1a1 mRNA expression at control levels, and preserved neurovascular integrity. Our results suggest that the neuroprotective mechanism of CBZ extends beyond Na+ channel blockade, acting as a multifaceted stabilizer of ionic homeostasis and of Na+/K+-ATPase expression in the hippocampal formation.