Ocimum sanctum extract preserves neuronal echotexture and controls seizure in lithium-pilocarpine induced status epilepticus rats

Abstract

Objective: To investigate the effect of Ocimum sanctum hydroalcoholic extract (OSHE) on seizure control and neuronal injury in rats with lithium-pilocarpine-induced status epilepticus (SE). Methods: SE was induced by administering lithium chloride followed by pilocarpine 24 h later. OSHE was administered either alone or in combination with valproate (VPA) 3 days before SE induction until 14 days post-SE induction. Seizure parameters were recorded on day 1 (0-3 h), day 1-3 and day 4-14 post-SE. On day 14 post-SE, neurobehavioural tests (elevated plus maze and passive avoidance) were done followed by total antioxidant capacity, neuron-specific enolase, immunohistochemistry, and electron microscopic assessment in the hippocampus and cortex tissue. Results: OSHE+VPA provided more significant seizure protection (75%) than VPA (62.5%), OSHE (62.5%), or SE control (12.5%) (overall P=0.003). The latency to stage-3/4 seizures was increased and the number of stage-3/4 seizures was reduced in all treatment groups compared to the SE control group (P=0.002 and <0.001, respectively). The OSHE+VPA group also had better memory retention than other treatment groups (P<0.001) in the passive avoidance test. Total antioxidant capacity level was significantly higher and neuron-specific enolase was lower in the OSHE and OSHE+VPA groups compared to the SE control group. Electron microscopic study showed significant myelin sheath damage (67.5%, P<0.05) and axonal degeneration (51.8%, P<0.001) in the hippocampus of the SE control group, which were alleviated by OSHE or OSHE+VPA treatment. In immunohistochemical analysis, the OSHE, OSHE+VPA, and VPA groups had a significantly higher number of viable neurons and less neuronal loss compared to the SE control in the hippocampus (P<0.001). Conclusions: OSHE either alone or in combination with VPA shows better seizure control by preservation of neuronal echotexture and reducing oxidative stress in the hippocampus.

Keywords

• status epilepticus; ocimum sanctum; seizure protection; neuronal injury; electron microscopy