Cannabidiol Modulates Hippocampal Neuronal Morphology and Attenuates Reactive Astrogliosis in Animal Model of Epilepsy

Intractable form of epilepsy is a major challenge worldwide, and despite an increasing number of medical therapies in the treatment of epilepsy, about one in three patients continues to experience seizures. This study evaluated the effects of cannabidiol on neuronal morphology and astrocytes in the hippocampus of epileptic rats. Adult Wistar rats (150-180 g) were grouped into acute, latent, and chronic phases of epilepsy. Each group was further subdivided into five subgroups A-E of eight rats each. Subgroups A, the control received corresponding vehicle volumes for the entire phases of epileptogenesis. Epilepsy was induced in subgroups B, C, D, and E by intraperitoneal administration of lithium chloride (127 mg/kg) 24 hours before pilocarpine (30 mg/kg). Seizures were allowed to last for 45 minutes and then terminated by diazepam (10 mg/kg). Subgroups C and D received 5 mg/kg and 10 mg/kg of cannabidiol respectively orally daily while subgroups E received 10mg/kg of sodium valproate. At the end of the three phases, the rats were sacrificed and their hippocampi were processed for histological and immunohistochemical assessment. Data were analysed using Analysis of Variance followed by the Newman-Keuls test for multiple comparisons. The Cornu Ammonis 1 and dentate gyrus across all phases of epilepsy showed loss of pyramidal neurons, dispersed granule cells, and glial fibrillary acidic protein expression in subgroups B. The expression wasremediated by cannabidiol. The increase in degenerating neurons in Subgroup B was significantly reversed by cannabidiol across the three phases. The study concluded that cannabidiol ameliorated chemically induced epilepsy.

Key Words: cannabidiol, epilepsy, hippocampus, pyramidal neurons, astrocytes