Electrophysiological, histopathological, and biochemical evaluation of the protective effect of probiotic supplementation against pentylenetetrazole‐induced seizures in rats

Abstract

Background and purposeResearch on the relationship between the gut microbiome and epilepsy is accumulating. The present study was conducted to evaluate the effect of probiotic supplementation on pentylenetetrazole (PTZ)‐induced seizures in rats.MethodsTwenty‐one adult male Wistar albino rats were included. The animals were divided into three groups of seven rats. Group 1 was a control group, whereas Group 2 rats received PTZ treatment and Group 3 rats had PTZ+PB (probiotic) treatment. For 6 weeks, Groups 1 and 2 were given saline (1 ml), whereas Group 3 had probiotic supplement. In the 5th week, tripolar electrodes were attached to the rats. Electrophysiological, behavioral, biochemical, and immunohistochemical evaluations were performed in the 6 weeks after the treatment.ResultsPB treatment significantly reduced seizures. In the PTZ group, expression levels of brain‐derived neurotrophic factor, nerve growth factor (NGF), and Sox2 (SRY sex‐determining region Y‐box 2) in rat brains decreased significantly compared to the control group, whereas the expression levels of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), total oxidant status (TOS), and nitric oxide (NO) levels increased. In the PTZ+PB group, NGF expression increased significantly compared to the PTZ group, whereas TNF‐α, IL‐6, TOS, and NO levels decreased. In histopathological examination, an abundance of necrotic neurons was notable in the PTZ group, which was less in the PTZ+PB group. In addition, body weight of the group supplemented with probiotics decreased after the treatment.ConclusionsOur results suggest that probiotic supplementation may alleviate seizure severity and exert neuroprotective effects by reducing neuroinflammation and oxidative stress and altering the expression of neurotrophins in epileptogenic brains.

Effect of dietary supplementation with Lactobacillus helveticus R0052 on seizure thresholds and antiseizure potency of sodium valproate in mice

“…For example, Wang et al ( 2022 ) found that probiotic supplementation reduced spontaneous seizure in the kainic acid-induced epilepsy model and the effect was accompanied with decreased level of inflammatory cytokines (IL-1 β, IL-6, and TNF-α), lipid peroxidation, DNA damage, and increased total antioxidant ability in the hippocampus. Decreased brain levels of IL-6, TNF-α, and nitric oxide following probiotic treatment were also reported in WAG/Rij rats (Aygun et al 2022b ) and in rats subjected to the PTZ seizure test (Aygun et al 2022a ). In a study by Wang et al ( 2019b ), L. helveticus R0052 exhibited anti-inflammatory properties by downregulating TLR2, TLR4, TLR5, NF-κB, and TNF-α transcription in liver, decreasing proinflammatory cytokines (IL-2, IL-6, IL-12, IL-17, TNF-α, RANTES, and MIP-3α) in serum, and enhancing the intestinal barrier of d -galactosamine-treated rats.…”

“…The second study showed that administration of probiotics after birth may decrease rotavirus-associated seizures in neonates (Yeom et al 2019 ). In animal studies, probiotics treatment reduced acute penicillin- (Kızılaslan et al 2022 ) and PTZ-induced seizures (Aygun et al 2022a ; Kilinc et al 2021 ), suppressed development of PTZ-induced kindling (Bagheri et al 2019 ; Tahmasebi et al 2020 ), ameliorated spontaneous seizures after kainic acid-induced status epilepticus (Wang et al 2022 ), and alleviated absence seizures in WAG/Rij rats with absence epilepsy (Aygun et al 2022b ).…”

The interplay between microbiota and brain-gut axis in epilepsy treatment

“…The intervention resulted in a decrease in epileptic activity levels, a significant reduction in seizure severity, and a partial improvement in spatial learning and memory in the epileptic rats. Importantly, the probiotic treatment also led to decreased concentrations of pro-inflammatory cytokines IL-6 and TNF-α, reduced levels of nitric oxide (NO) and malondialdehyde (MDA), increased total antioxidant capacity (TAC), and elevated levels of GABA in the brain tissue (Bagheri et al, 2019;Aygun et al, 2022a;Aygun et al, 2022b). Additional research utilizing animal models of epilepsy has corroborated the anti-seizure effects of probiotics.…”

Role of Short Chain Fatty Acids in Epilepsy and Potential Benefits of Probiotics and Prebiotics: Targeting “Health” of Epileptic Patients

“…VSL#3 reduced seizure severity and decreased proinflammatory cytokines that increase BBB permeability, elevate CNS cytokine levels, and increase neuronal excitability. VSL#3 also restored the increased total oxidant status in the brain [ 157 ]. The most recent study using VSL#3 induced focal seizures in rats via penicillin G. VSL#3 increased the latency and decreased the spike frequency of focal seizures, while decreasing proinflammatory cytokines and oxidative factors such as NO [ 158 ].…”