Bromocriptine Mesylate Protects against Status Epilepticus and Temporal Lobe Epilepsy: Neurobehavioral, Histopathological and Neurochemical Evidences

Background: Dopamine (DA) plays a major role in the control of epileptic seizures arising in the limbic system, through D1/D2 receptor-mediated signaling.

Objective: The study was intended to investigate whether bromocriptine mesylate (BRC), a dopamine (D2) receptor agonist, has an anti-seizure property, attenuates oxidative stress and neuronal morphological alterations against pilocarpine induced status epilepticus (SE) in mice, using sodium valproate (SVP) as comparator AED.

Materials and Methods: SVP (300 mg/kg) and BRC (6 &10 mg/kg) were administered orally once daily for a period of 4 weeks followed by pilocarpine (300 mg/kg, i.p) to induce SE. The convulsions were monitored for 2 hrs post pilocarpine injection. At 2 hrs post pilocarpine injection hippocampal malondialdehyde, glutathione reduced, glutathione peroxidase, glutathione reductase and catalase activities were measured. While hippocampal histopathological assessment of neuronal injury was performed 24 hrs post pilocarpine injection.

Results: We report that SVP (300 mg/kg) and BRC (6 &10 mg/kg) were able to reduce seizure severity score (P<0.001, P<0.01, P<0.05), attenuate oxidative damage in lipids and proteins, restore depletion in hippocampal glutathione reduced, glutathione peroxidase and glutathione reductase activities compared to toxic/pilocarpine control. Contrary catalase levels were strengthened as like pilocarpine control. In addition SVP (300 mg/kg) and BRC (6 & 10 mg/kg) protected against degeneration in hippocampal CA1, CA2, CA3 & DG regions (P<0.001, P<0.01, P<0.05) compared to pilocarpine control.

Conclusions: The present study highlights the prominent dysregulation of dopaminergic system in seizures and perspectives for the development of novel therapeutic approaches acompassing dopaminergic drugs in amelioration of epileptic seizures especially status-epilepticus and temporal lobe epilepsy.