Probiotics Co-administered with LCM Enhance Antiepileptic Efficacy in the Experimental Post-traumatic Epilepsy Model

Abstract

The aim of the presented study was to investigate the effects of prebiotic inulin, probiotic VSL#3 (mixture of bacteria from 7 different species and 8 strains) and synbiotic (inulin + VSL#3) supplements applied together with lacosamide (LCM) on post-traumatic epilepsy (PTE). In addition, effectiveness of the relevant treatments on comorbid problems related to learning and memory, anxiety, motor performance and pain threshold that may develop together with seizures due to traumatic brain injury (TBI) and PTE was also examined using behavioral tests. In experiments, adult male Sprague-Dawley rats, divided into 6 groups, were given 30 mg/kg LCM or 1000 mg/kg inulin together with LCM as prebiotic, VSL#3 mixture containing 10 × 10⁹ CFU/kg bacterial colonies as probiotic and (inulin + VSL#3) as synbiotic for 28 days by oral gavage after mild-TBI was induced by weight-drop method and electroencephalogram electrodes were placed. In order to reveal the tendency to trauma-induced seizures, PTE was modeled by injection of 30 + 15 + 15 mg/kg pentylenetetrazole at subconvulsant doses at 30-min intervals on 7th, 14th, 21st and 28th days after TBI and seizures were scored according to Racine scale. Locomotor, cognitive and pain-related behaviors of animals other than seizures were also examined using open field, rotarod, elevated plus maze, radial arm maze, dynamic plantar and thermal plantar tests. It was determined that LCM applied alone was effective in seizure control related to PTE, but probiotic supplement in form of LCM + VSL#3 provided more effective seizure control. In addition, it was determined that probiotic VSL#3 applied together with LCM increased locomotor activity, both VSL#3 and inulin prevented the disorder in forced motor activity caused by LCM, and VSL#3 + inulin applied together with LCM increased mechanical pain threshold. It was concluded that probiotic VSL#3 combined with antiepileptic LCM provides more effective seizure control by strengthening the antiepileptic activity of LCM in management of PTE.