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

BACKGROUND AND PURPOSE: Research 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. METHODS: Twenty-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. RESULTS: PB 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. CONCLUSIONS: Our 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.

Probiotic supplementation alleviates absence seizures and anxiety- and depression-like behavior in WAG/Rij rat by increasing neurotrophic factors and decreasing proinflammatory cytokines.

AIM: Epilepsy is one of the most common chronic brain disorders that affect millions of people worldwide. In the present study, we investigated the effects of probiotic supplementation on absence epilepsy and anxiety-and depression-like behavior in WAG/Rij rats. MATERIAL AND METHOD: Fourteen male WAG/Rij rats (absence-epileptic) and seven male Wistar rats (nonepileptic) were used. The effects of probiotic VSL#3 (12.86 bn living bacteria/kg/day for 30 day/gavage) on absence seizures, and related psychiatric comorbidities were evaluated in WAG/Rij rats. Anxiety-like behavior was evaluated by the open-field test and depression-like behavior by the forced swimming test. In addition, the brain tissues of rats were evaluated histopathologically for nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], SRY sex-determining region Y-box 2 [SOX2] and biochemically for nitric oxide [NO], tumor necrosis factor-alpha [TNF-α] ,and Interleukin-6 [IL-6]. RESULTS: Compared to Wistar rats, WAG/Rij rats exhibited anxiety- and depression-like behavior, and had lower BDNF, NGF and SOX2 immunoreactivity, and higher TNF-α, IL-6 levels in brain tissue. VSL#3 supplementation reduced the duration and number of spike-wave discharges (SWDs) and exhibited anxiolytic or anti-depressive effect. VSL#3 supplement also increased the NGF immunoreactivity while decreasing IL-6, TNF-α and NO levels in WAG/Rij rat brain. CONCLUSION: The findings of the present study showed that neurotrophins, SOX2 deficiency, and pro-inflammatory cytokines may play a role in the pathogenesis of absence epilepsy. Our data support the hypothesis that the probiotics have anti-inflammatory effect. The present study is the first to show the positive effects of probiotic bacteria on absence seizures and anxiety- and depression-like behavior.