Evaluation of the effects of lactobacillus rhamnosus administration on penicillin-induced epileptiform activity in rats

Epilepsy is a neurological disease with a high prevalence that can be seen in one out of every hundred people, which is not yet fully treatable and impairs quality of life. In addition to antiepileptic drugs used in the treatment of epilepsy, many new studies are carried out to understand the mechanism and develop new drugs for treatment. The view that microbiota may also be effective in the mechanisms of epilepsy has gained importance. The main mechanism in the treatment of epilepsy is to strengthen the GABAergic system. Lactobacillus rhamnosus, a probiotic bacterium found in the microbiota, has been shown in studies to produce gamma-aminobutyric acid (GABA) in the colon. Therefore, our study aimed to investigate the effect of L. rhamnosus bacteria, a natural member of the microbiota, on experimental epilepsy and free radical formation in rats. In this study, 70 adult Wistar rats were used. Test animals were divided into three basic groups: sham, control (penicillin), and L. rhamnosus (LBR). LBR groups were given 1 mL of 1x1010 cfu/mL LBR daily by gavage for 4 and 10 weeks. While the rats were under anesthesia with urethane, the part of the skull above the left cortex was removed and electrodes were placed in the somatomotor area. After the intracortical injection of penicillin, ECoG recording was performed for 120 minutes. Besides, these recordings were converted into data and analyzed by a software program. Experimental analyses were evaluated regarding latency, spike-wave frequency, and amplitude of initial epileptiform activity. Furthermore, to evaluate the effects of L. rhamnosus probiotic supplement on GABA levels and antioxidant mechanisms, serum and brain tissue samples were taken from the experimental groups and the ELISA test method was employed. GABA, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) values in serum and brain tissue samples were measured by the ELISA test method. It was observed that the epileptiform activity initiation latency was prolonged in the groups in which LBR and DZM were applied together. It has been shown that LBR dramatically reduces the frequency of total epileptiform activity spikes compared to the control group. A similar decrease was observed in the epileptiform activity spike wave amplitude of LBR. This relevance was noticed to be more remarkable, especially in the LBR10 and LBR-DZM-10 groups. When the CAT, SOD, and GPx levels of the samples taken from the LBR-applied groups were compared with the control group, no significant relationship was found between them. While the serum GABA level from the LBR-treated groups was similar to the control group, the GABA level of the LBR4 group in the brain tissue was found to be higher than the control group. In conclusion, it is thought that probiotics may have an important antiepileptic effect in developing and treating epilepsy. Evaluation of the correlation between neurodegenerative diseases and probiotics will be possible with further clinical and experimental studies. Keywords: Electrocorticography, Epilepsy, GABA, Lactobacillus rhamnosus, Rat, Oxidative Stress