No abstract

No abstract

Background and Aim: Epilepsy is a common brain disorder. Brain function can be affected by the intestinal microflora. The intestinal microflora have a major role in modulating immune responses, producing essential metabolites and mediating neurotransmitters. Antibiotics can affect and reduce these roles and functions by eliminating the intestinal microflora. The aim of this study was to investigate the effect of intestinal natural micro flora removal on seizure susceptibility and seizure behavior modification with the use of probiotics in male Wistar rats. Methods & Materials: This study was performed on 32 male Wistar rats with weight range 200-250 gr. The animals were randomly divided into four groups: 1. Control group; 2. Antibiotic group; 3. Probiotic group and 4. Antibiotic + probiotic group. To remove the microflora, antibiotics (neomycin, ampicillin, and metronidazole) for three weeks and for replacement of microflora, probiotics (Lactobacilli casei, Lactobacillus acidophilus and Bifidobacterium bifidum) for four weeks were administered. Seizures were performed by intraperitoneal injection of pentylentrazole. The microflora was examined by the MRS Agar medium and the Pure Plate method. The data were statistically analyzed in Graph Pad Prism V. 8. Ethical Considerations: This study was approved by the Research Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1395.176). Results: The use of antibiotics lead to decrease the number of intestinal bacteria (P<0.0001), increased the severity and stability of seizure stages (P<0.05) and decreased the time delay of seizure onset (P<0.05) compared to the control group. Probiotic consumption by modifying the intestinal microflora (P<0.0001) reduced the severity of seizure and increased the time delay of seizure onset (P<0.05). Conclusion: Elimination of microflora has the potential to induce seizures, which can be compensated by administration of probiotics.

In the present study, we aimed to evaluate the therapeutic efficacy of β-d-mannuronic acid (M2000) in a rat model of epilepsy. Pentylenetetrazole (PTZ)-induced kindling model was applied in 30 Wistar rats divided into 3 groups through a total of 14 injections, while the rats in the drug-tested group were treated with M2000. Animals were observed for various seizure stages, delay that the rats developed in stages 2 and 5, and the duration of stage 5 seizures. After the last injection, the animals were euthanized and analysis was conducted in the brain for the various gene expression profiles along with histopathology assessments. Pretreatment of animals with M2000 has significantly accelerated epilepsy outcomes promptly following the first PTZ injection (mean ± standard deviation [SD] for seizure stage in the M2000 group was 3.12 ± 1.55 vs 0.75 ± 1.03 for control, P = 0.004). Notably, the mean (±SD) on the latency phase 2 and 5 seizures was lower in the M2000 group compared with control group (79.4 ± 30.7 vs 133.0 ± 38.4, P < 0.001, and 126.1 ± 27.6 vs 233.3 ± 142.8, P = 0.001, respectively). Finally, the mean (±SD) duration of phase 5 seizures was significantly higher in the M2000 pretreated group compared with control rats (344 ± 54 vs 197 ± 94, P < 0.001). Histological findings on the hippocampus showed no significant differences among all groups. Elevated expression level of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon-γ, and cyclooxygenase-2 was seen in the PTZ-induced kindling group. An elevated expression level of IL-10 was observed in the brains of rats in the M2000 treat group. Our results indicated that rats pretreated with M2000 were predisposed to epilepsy promptly after the first PTZ injection.

Background: The KW-2449 is a novel multikinase inhibitor that inhibits FLT3, ABL, ABL-T315I, and Aurora A. FLT3 and Aurora A kinases play an important role in the pathogenesis of multiple sclerosis (MS). KW-2449 could modulate immune cells but the immunomodulatory effects of KW-2449 on experimental autoimmune encephalomyelitis (EAE) have not been investigated yet. The aim of the present study is to investigate the effects of KW-2449 on EAE mouse model. Methods: In this study, C57BL/6 EAE mice were orally treated with (10 mg/kg/day) KW-2449 solution and compared with both EAE and control mice. Following the treatment, histological analyses were performed on brain and cerebellums to evaluate the pathological score. The gene expression levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) were measured using qRT-PCR. The serum levels of TNF-α, IL-6, CCL-2 and MMP-2 were determined by using quantitative enzyme-linked immunosorbent assay (ELISA). Results: The results indicated that the clinical score, the infiltration of inflammatory cells and the demyelination in EAE mice treated with KW-2449 decreased significantly compared to control groups. KW-2449 also decreased TNF-α, IL-6, CCL-2 inflammatory cytokines and MMP-2 in both brain mRNA expressions and serum levels of EAE mice. Conclusion: The KW-2449, aging as a multi-kinase inhibitor, modulates the inflammatory responses of cytokine cascades either in brain or in plasma and reduces EAE pathogenesis manifestation.