Neuroprotective effect of crocetin against epileptiform activity induced by microinjection of penicillin into the somatosensory cortex of the brain: Role of GABAA-benzodiazepine receptor, oxidative stress and inflammation.

Crocetin, a major compound of saffron, exhibits various biological activities, including neuroprotective properties. Our study sought to evaluate the effect of crocetin on epileptiform discharges in the primary somatosensory cortex (S1) neurons following microinjection of penicillin in urethane anesthetized rats. Electrocorticographic (ECoG) recordings were performed for a 180-min period. The frequency and amplitude of spikes were recorded in 30-min intervals for 180-min. The areas under the curve (AUC) of the above-mentioned spike alterations were calculated. Biochemical parameters of the cerebrum were also determined. Intraperitoneal (IP) injection of crocetin and intracerebroventricular (ICV) administration of diazepam and flumazenil (an agonist and an antagonist of GABAA-benzodiazepine receptors, respectively) were done before penicillin administration. Infusion of penicillin (500 IU/2.5 μL) into the S1 of the brain triggered epileptiform activity with spike wave patterns. Prior administration of crocetin (20 and 40 mg/kg, IP) and diazepam (4 μg/μL, ICV) alleviated the frequency and amplitude of spikes. Microinjection of flumazenil (4 μg/μL) prevented the reducing effects of crocetin (40 mg/kg) and diazepam (4 μg/μL). The AUC results supported the impact of the aforementioned treatments. On the other hand, IP urethane injection and intracortical penicillin microinjection reduced superoxide dismutase (SOD) activity and total antioxidant capacity (TAC) content, while it simultaneously increased malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) levels. Crocetin (20 and 40 mg/kg) ameliorated biochemical alterations. These results showed that crocetin could reduce penicillin-induced epileptiform activity through GABAA-benzodiazepine receptor, as well as anti-oxidative and anti-inflammatory mechanisms.