Supriya Sharma
CSIR-Institute of Himalayan Bioresource Technology, India
Title: Investigating the Cardiovascular Changes in Rat Model of Lithium-Pilocarpine Induced Spontaneous Recurrent Seizures
Biography
Biography: Supriya Sharma
Abstract
Background: Epilepsy is a chronic neurological condition that is mainly characterized by occurrence of spontaneous recurrent seizures. Study has also shown that temporal lobe seizure lead to development of ventricular fibrillation, shortening or prolongation of QT intervals, producing prolongation in the action potential, propensity to malignant tachyarrhythmia’s thus risking cardiac damage. These cardiac repercussions often lead to life-threatening condition known as “Sudden Death in Epilepsy or SUDEP”.
Methods: The present study was envisaged to understand the cardiac changes during different phases of epileptogenesis and molecular changes in rat lithium-pilocarpine (Li-pilo) model of epilepsy. The animals were exposed to Li-pilo for induction of spontaneous recurrent seizures (SRS). Non-invasive blood pressure and electrocardiography was recorded at 7th, 28th and 75th day after pilocarpine administration, considered as latent, initial SRS and late SRS phases, respectively. Following electrocardiography on the day 75, blood was collected for serum biochemistry and animals were sacrificed for cardiac histopathology, specific protein levels and gene expression.
Findings: Latent mean arterial pressure decreased as compared to the basal, whereas it was increased during initial and late SRS phases. Prolonged QTc interval was observed during late SRS as that of basal and latent phase. A significant increase in the serum level of lactate dehydrogenase and creatine kinase was observed in epileptic animals, along with hypertrophy, degenerative changes and fibrosis in heart sections. Increase in the expression of TGF-β, S6 ribosomal, phospho-S6 ribosomal, HIF-1α, Na+/K+-ATPase α1, collagen I, mTOR and phospho-mTOR proteins was observed in the cardiac tissue. The cardiac mRNA level of HIF-1α, mTOR, Rps6, Scn1b, Scn3b, Nav1.5 and TGF-β was also increased as compared to control.
Conclusion: The results concluded 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.