Effect of prednisolone in a kindling model of epileptic seizures in rats on cytokine and intestinal microbiota diversity.

Epilepsy is a neurological disease characterized by spontaneous and recurrent seizures. Epileptic seizures can be initiated and facilitated by inflammatory mechanisms. As the dysregulation of the immune system would be involved in epileptogenesis, it is suggested that anti-inflammatory medications could impact epileptic seizures. These medications could potentially have a side effect by altering the structure and composition of the intestinal microbiota. These changes can disrupt microbial homeostasis, leading to dysbiosis and potentially exacerbating intestinal inflammation. We hypothesize that prednisolone may affect the development of epileptic seizures, potentially influencing the diversity of the intestinal microbiota and the regulation of pro-inflammatory cytokines in intestinal tissue. This study aimed to evaluate the effects of prednisolone treatment on epileptic seizures and investigate the effect of this drug on the bacterial diversity of the intestinal microbiota and markers of inflammatory processes in intestinal tissue. We used Male Wistar rat littermates (n = 31, 90-day-old) divided into four groups: positive control treated with 2 mg/kg of diazepam (n = 6), negative control treated with 0.9 g% sodium chloride (n = 6), and the remaining two groups were subjected to treatment with prednisolone, with one receiving 1 mg/kg (n = 9) and the other 5 mg/kg (n = 10). All administrations were performed intraperitoneally (i.p.) over 14 days. To induce the chronic model of epileptic seizures, we administered pentylenetetrazole (PTZ) 25 mg/kg i.p. on alternate days. Seizure latency (n = 6 - 10) and TNF-α and IL-1ß concentrations from intestinal samples were measured by ELISA (n = 6 per group), and intestinal microbiota was evaluated with intergenic ribosomal RNA (rRNA) spacer (RISA) analysis (n = 6 per group). The prednisolone treatment demonstrated an increase in the latency time of epileptic seizures and TNF-α and IL-1ß concentrations compared to controls. There was no statistically significant difference in intestinal microbiota diversity between the different treatments. However, there was a strong positive correlation between microbial diversity and TNF-α and IL-1ß concentrations. The administration of prednisolone yields comparable results to diazepam on increasing latency between seizures, exhibiting promise for its use in clinical studies. Although there were no changes in intestinal microbial diversity, the increase in the TNF-α and IL-1ß cytokines in intestinal tissue may be linked to immune system signaling pathways involving the intestinal microbiota. Additional research is necessary to unravel the intricacies of these pathways and to understand their implications for clinical practice.

Reduction of seizures and inflammatory markers by betamethasone in a kindling seizure model.

Epilepsy is a chronic disease characterized by an ongoing predisposition to seizures. Although inflammation has emerged as a crucial factor in the etiology of epilepsy, no approaches to anti-inflammatory treatment have been clinically proven to date. Betamethasone (a corticosteroid drug used in the clinic for its anti-inflammatory and immunosuppressive effects) has never been evaluated in attenuating the intensity of seizures in a kindling animal model of seizures. Using a kindling model in male wistar rats, this study evaluated the effect of betamethasone on the severity of seizures and levels of pro-inflammatory interleukins. Seizures were induced by pentylenetetrazole (30 mg/kg) on alternate days for 15 days. The animals were divided into four groups: a control group treated with saline, another control group treated with diazepam (2 mg/kg), and two groups treated with betamethasone (0.125 and 0.250 mg/kg, respectively). Open field test was conducted. Betamethasone treatments were effective in reducing the intensity of epileptic seizures. There were lower levels of Tumor Necrosis Factor-α and interleukin-1ß in the cortex, compared to the saline group, on the other hand, levels in the hippocampus remained similar to the control groups. There was no change in the levels of interleukin-6 in the evaluated structures. Serum inflammatory mediators remained similar. Lower quantities of inflammatory mediators in the central nervous system may have been the key to the reduced severity of seizures on the Racine scale.

Aerobic exercise, alone or combined with an anti-inflammatory drug, reduces the severity of epileptic seizures and levels of central pro-inflammatory cytokines in an animal model of epileptic seizures.

Epilepsy is a chronic neurological disorder and there is increasing evidence about the role of inflammation in epileptogenesis. These findings have spurred the search for new immunomodulatory approaches that can improve prognosis. Using an animal model of chemically-induced epileptic seizures, we tested exercise alone as non-pharmacological therapy, and exercise combined with an anti-inflammatory drug. Five groups were used: sedentary, diazepam, aerobic exercise alone, aerobic exercise combined with an anti-inflammatory drug, and naive control. Our goal was to compare the severity of the epileptic seizures between groups as well as seizure latency in a pentylenetetrazole-induced paradigm. Cytokine levels (IL-1ß, TNF-α, and IL-10) were measured. Both exercise groups showed a reduction in seizure severity and lower levels of pro-inflammatory cytokines in the cortex, while the levels of cytokines in the hippocampus remained unaffected.

Parameters of Oxidative Stress and Behavior in Animals Treated with Dexametasone and Submitted to Pentylenetetrazol Kindling.

BACKGROUND AND PURPOSE: Oxidative stress (OS) is defined as an excessive production of reactive oxygen species that cannot be neutralized by the action of antioxidants, but also as an alteration of the cellular redox balance. The relationship between OS and epilepsy is not yet fully understood. The objective of this study was to evaluate the effect of dexamethasone on OS levels and memory in the kindling model induced by pentylenetetrazole. METHODS: The animals were divided in six groups: control group that received no treatment, vehicle group treated with vehicle, diazepam group, and groups treated with dexamethasone (1, 2 and 4 mg/kg). Treated animals received pentylenetetrazole in alternated days for 15 days. Inhibitory avoidance test was conducted in 2 hours and OS was evaluated after animal sacrifice. RESULTS: Regarding the treatment with dexamethasone, there was no significant difference when compared to the control groups in relation to the inhibitory avoidance test. On OS levels, there was a decrease in catalase activity levels in the hippocampus and an increase in thiobarbituric acid reactive substances and glutathione peroxidase levels in the hippocampus. CONCLUSIONS: The anticonvulsant effect of dexametasone remains uncertain. Immunological mechanisms, with the release of cytokines and inflammatory mediators, seem to be the key to this process. The mechanisms that generate OS are probably related to the anticonvulsant effects found.

Inflammatory signs and epileptic crisis in patients admitted in an emergency unit.

OBJECTIVE: To evaluate inflammatory signs presented in medical records of patients with a main diagnosis of epileptic seizures, admitted in an emergency unit. METHOD: Cross-sectional and retrospective study. The sample was composed of 191 medical records, from children, adolescents, adults, and elders, with a clinical diagnosis of epileptic seizures, admitted between June 2016 and June 2017 at the emergency unit of a hospital in Porto Alegre/RS. RESULTS: The prevalent inflammatory signs were tachypnea (33.5%) and/or fever (27.2%) associated with leukocytosis (P=0.030). Children/adolescents had seizures less frequently (P=0.010) and these were due to fever (P=0.000). Adults presented seizures more frequently (P=0.006), which were related to medication/intoxication (P=0.000). In elders, seizures occurred due to metabolic or circulatory abnormalities (P=0.000), less often due to fever (P=0.005). CONCLUSION: Seizures are related to fever and tachypnea, being caused by different etiologies according to age, being more frequent in adults. Fever is related to leukocytosis, regardless of age.

Effect of dexamethasone on seizures and inflammatory profile induced by Kindling Seizure Model.

The objective of this study was to evaluate the effect of dexamethasone, on the severity of seizures and levels of pro-inflammatory interleukins in animals with kindling model induced by pentylenetetrazole (20 mg/kg) in alternated days for 15 days of treatment. The animals were divided into five groups: control group given saline, a group treated with diazepam (2 mg/kg) and groups treated with dexamethasone (1, 2 and 4 mg/kg). Open field test was conducted. The treatment with dexamethasone decreased the severity of seizures, also decreased TNF-alpha and Interleukin 1 beta levels in the hippocampus and TNF-alpha level in the serum.