Abstracts

Rationale: Studies have associated the brain inflammation as a causative factor for neural excitability and decreased neurogenesis in epilepsy. Thymoquinone (TQ), active constituent of Nigella sativa seeds has anti-inflammatory and neuroprotective roles. Aim of the present study was to investigate the effects of thymoquinone on frequency of spontaneous recurrent motor seizures (SRMS) and aberrant mossy fiber sprouting and neuroprotection in kainic acid model of chronic temporal lobe epilepsy in middle aged rats. Methods: Status epilepticus was induced in 12 months old Wistar rats by injecting kainic acid (0.5µg) into the lateral ventricles steriotaxically and were divided into two groups: i) Lesion only (LO) - Remained without any treatment, ii). Lesioned and treated with TQ for 3 weeks (10mg/kg, ip, L+TQ, n=6 in both groups). These rats were video monitored (between 3.0 and 3.5 month post lesion period) for frequency of spontaneous recurrent motor seizures(SRMS) analysis. After quantifying seizure frequency, rats in both groups were sacrificed along with age matched normal control rats (NC, n=6)., brain was dissected, brain sections were immunostained with ZnT3 immunostaining to stain mossy fibers. Density of aberrantly sprouted mossy fiber were quantified by image-J software. Number of neurons in the dentate hilus and CA3 region were quantified. Data were analyzed with one way ANOVA or Student's t-test. Results: TQ treatment reduced the SRMS frequency significantly compared to control group (4±0.1 seizures/day in LO vs 1.5±0.2 in TQ treated group) seizures/day, Student's t-test, P<0.001). Treatment with TQ suppressed the aberrant mossy fiber sprouting significantly compared to LO group in septal and temporal hippocampus (30-40%, P<0.001). Number of neurons in the dentate hilus and CA3 regions in septal and temporal hippocampus was significantly more in TQ treated group compared to LO (20-30% in both regions, P<0.001). Conclusions: Our data suggest that treatment with thymoquinone reduces SRMS frequency which may be due to decreased aberrant mossy fibers sprouting. Enhanced neuronal survival in dentate hilus and CA3 region due to neuroprotective role of thymoquinone immediately after kainic acid induced lesion in the hippocampus might have limited the mossy fiber sprouting. Results of the present experiment signifies the use of TQ as new antiepileptic drug to treat temporal lobe epilepsy in humans in future.