Background: Alteration in electrophysiology, leading to cardiac dysfunction and subsequently
a nontraumatic death is a complication of epilepsy known as “SUDEP” (Sudden Unexpected
Death in Epilepsy).
Aims: The present study was designed to understand the molecular changes and cardiac parameters
during different phases of epileptogenesis in lithium-pilocarpine (Li-pilo) rat model of epilepsy.
Methods: The animals were exposed to Li-pilo to induce Spontaneous Recurrent Seizures (SRS). Noninvasive
blood pressure and electrocardiography was recorded at 7th, 28th and 75th day following pilocarpine
administration, considered as latent, initial and late SRS phases, respectively. The serum biochemistry,
cardiac histopathology, protein and mRNA expressions were studied, following electrocardiography
on day 75.
Results: The mean arterial pressure decreased during the latent phase, thereafter it progressively increased
during the initial and the late SRS phases, as compared to the basal and the latent phase. Histopathological
analysis of the heart sections indicated hypertrophy, degenerative changes and fibrous
tissue deposition in epileptic animals, along with increased levels of lactate dehydrogenase and creatine
kinase-MB in the serum. The expression of HIF-1α, phospho-S6, phospho-mTOR, TGF-β, collagen
I and Na+/K+-ATPase α1 proteins, and mRNA levels of HIF-1α, mTOR, Rps6, Scn1b, Scn3b,
Nav1.5 and TGF-β were increased in the cardiac tissue of epileptic animals, as compared to control.
Conclusion: Our results conclusively showed that Li-pilo-induced SRS leads to cardiac dysfunction
via mTOR pathway upregulation, thus suggested the regulatory control of mTOR pathway as a potential
target for SUDEP management.