Nesfatin­1 exerts anticonvulsant effect by reducing oxidative stress in experimental epilepsy model.

Neuropeptides play an important role in the pathogenesis of epilepsy. In the present study, the effect of nesfatin­1, a neuropeptide, was investigated on penicillin­induced epilepsy model. Epileptiform activity was induced by an injection of penicillin into the somatomotor cortex at 56 albino Wistar rats. Nesfatin­1 (i.c.v.) was administered at five different doses (12.5, 25, 50, 100, and 200 pmol) 30 min after a penicillin administration. Astressin 2B, a corticotropin­releasing factor (CRF) receptor antagonist, was administered 10 minutes later the effective dose of nesfatin­1 (50 pmol, i.c.v.). Superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) levels in cerebrum were analysed by ELISA method. Nesfatin­1, at the doses of 25, 50 and 100 pmol, significantly reduced the frequency of epileptiform activity. However, none of the doses of nesfatin­1 had any effect on the amplitude of epileptiform activity. Astressin 2B alone did not show any effect on epileptiform activity. In addition, astressin 2B had no effect on the anticonvulsant effect of nesfatin­1. Nesfatin­1 (at the doses of 25, 50, 100 pmol) did not alter SOD and GSH levels, but significantly increased the GPx and GR levels. Nesfatin­1 (at a dose of 50 pmol) significantly decreased the MDA level in the cerebrum. Nesfatin­1 shows anticonvulsant effect and astressin 2B did not affect the anticonvulsant effect of nesfatin­1. We suggest that nesfatin­1 has oxidative stress­mediated anticonvulsant effect in the penicillin­induced epileptic activity.

Physical exercise and 5-hydroxytryptophan, a precursor for serotonin synthesis, reduce penicillin-induced epileptiform activity.

AIM: Previous studies have shown that 5- hydroxytryptophan (5-HTP) and exercise play an important role in the synthesis of serotonin independently. The effects of the treadmill exercise and 5- hydroxytryptophan (5-HTP) on seizure mechanisms created by epileptiform activity with penicillin model were investigated in rats. METHOD: A total of 28 male albino Wistar rats were randomly divided into four groups: exercise (Ex), Control (Cnt), 5-hydroxytryptophan (5htp) and 5-hydroxytryptophan + exercise (5htpEx) groups. Treadmill exercise and gavage (25 mg/kg/day) were administered five days a week for ten weeks. Electrocorticogram data were recorded for 3 h at the end of the protocol using the Power-Lab data acquisition system. Spike frequency, amplitude, and latency time were analyzed offline. The significant differences among the groups were evaluated by one-way analysis of variance (ANOVA). RESULTS: Spike frequency was observed at the highest level from the 20th minute in the Cnt group, and this continued until the end of the recording. The 5-HTP alone group did not affect epileptiform activity. At the 80th minute of penicillin injection, the epileptiform activity in the 5htpEx group decreased significantly compared with the Cnt, and this significance continued until the 110th minute. There was no statistical difference in the amplitude values of the groups. The 5htpEx group was significantly higher than both the Cnt and Ex group in the seizure latency times. CONCLUSIONS: It was determined that exercise reduced the spike number and delayed seizure significantly by potentiating the effect of 5-HTP. Given that 5-HTP used in combination with exercise can perform useful actions such as reducing seizure sensitivity and consequently improving the quality of life for individuals with epilepsy, it may be a potential candidate for the treatment of epilepsy in nonpharmacological methods.

The effects of moderate running exercise and L-tyrosine on penicillin-induced epileptiform activity in rats.

Regular exercise and amino acid supplementation, popular approaches toward the reduction of epileptic seizures, have been extensively researched. This study was conducted to evaluate the effects of treadmill exercise and L-tyrosine treatment on the frequency and amplitude of epileptiform activity in rats. A total of 32 male albino Wistar rats were randomly divided into four groups: control, exercise, L-tyrosine, and exercise + L-tyrosine. L­tyrosine was supplemented by oral gavage (500 mg/kg/day, 2.5 mL solution). The treatments were performed 5 days a week for 10 weeks. The rats were anesthetized and then administered 500 IU penicillin into the left cerebral cortex using a microinjector and electrocorticogram (ECoG) activity was recorded for 3 hours using a Power Lab data acquisition system. The frequency and the amplitude of the ECoG recordings were analyzed offline. Compared to the control group, spike frequency decreased significantly in all other groups. There was no statistically significant difference between the groups in terms of spike amplitude and latency. In this study, the effects of regularly administered treadmill exercise and L-tyrosine use on epileptiform activity were examined and evaluated together for the first time. The results of this study showed that regular exercise and L-tyrosine use decreased epileptiform activity. Further research and clinical trials are needed to investigate the extent to which L-tyrosine and physical activity interfere with the epileptic state by investigating different doses of L-tyrosine and different severity/ time/type of exercise protocols.

The interaction between P2X7Rs and T-type calcium ion channels in penicillin-induced epileptiform activity.

Limited information exists on the link between purinergic class P2X7 receptors (P2X7Rs) and calcium ion channels in epilepsy; no data has been reported regarding the interaction between P2X7Rs and T-type calcium ion channels in epilepsy. Thus, this study is an evaluation of the role that T-type calcium ion channels play in the effect of P2X7Rs on penicillin-induced epileptiform activity. In the first set of experiments, P2X7R agonist BzATP (at 25-, 50-, 100- and 200-µg doses), P2X7R antagonist A-438079 (at 5-, 10-, 20- and 40-µg doses) and T-type calcium ion channel antagonist, NNC-550396 were administered for electrophysiological analyses 30 min after penicillin injection (2.5 µl, 500 IU). In the second set of experiments, the effective doses of these substances were used for biochemical analyses. Malondialdehyde (MDA), advanced oxidation protein product (AOPP), glutathione (GSH), glutathione reductase (GR), glutathione peroxide (GPx), catalase (CAT) and superoxide dismutase (SOD) levels were measured in the cerebrum, cerebellum and brainstem of rats. BzATP (100 µg, icv) increased the mean frequency of epileptiform activity, whereas A-438079 (40 µg, icv) and NNC-550396 (30 µg, ic) reduced it. Both A-438079 and NNC-550396 reversed BzATP's proconvulsant action. BzATP increased lipid peroxidation and protein oxidation; it also altered other antioxidant enzymes measured in this study, which were all then reversed via A-438079 and NNC-550396, at least in the cerebrum. The electrophysiological and biochemical analysis of present study suggest that P2X7Rs and its interaction with T-type calcium ion channels play an important role in the experimental model of epilepsy.

Proconvulsant Effect of Papaverine on Penicillin-Induced Epileptiform Activity in Rats.

AIM: Papaverine is a vasodilator agent that is an opium alkaloid. It exhibits its effects by inhibiting the phosphodiesterase enzyme. Papaverine administration is widely used to avoid symptomatic vasospasm after subarachnoid hemorrhage. We aimed, in this research, to study the effects of papaverine on the epileptic discharges stimulated by penicillin. MATERIAL AND METHODS: Adult female Wistar rats (220±30 g) were included in this research (n=30). Rats were anesthetized with urethane (1.25 g/kg) and then the left cerebral cortex was reached by opening a burr hole with a drill. Penicillin G sodium salt (500 IU)(200 IU/1 µl) was injected into the left lateral ventricle to produce epileptiform activity. Thirty minutes before penicillin G sodium injection, papaverine was administered at doses of 5, 10, 20 or 40 mg/kg intraperitoneally. RESULTS: There was no significant difference in spike frequency between the control group and the groups given 5 mg/kg, 10 mg/ kg or 40 mg/kg papaverine, while 20 mg/kg papaverine significantly increased the spike frequency (p < 0.05). CONCLUSION: Papaverine augments the epileptiform activity produced by penicillin injection. It is important to remember that papaverine might induce convulsions in patients who have epilepsy. More research is required to understand the mechanisms of the proconvulsant influence of papaverine in epilepsy.

Protective effects of melatonin and omega-3 on the hippocampus and the cerebellum of adult Wistar albino rats exposed to electromagnetic fields.

The purpose of the study was to investigate the effects of pulsed digital electromagnetic radiation emitted by mobile phones on the central nervous system of the adult Wistar albino rats. The study evaluated structural and functional impacts of four treatment arms: electromagnetic field (EMF) exposed; EMF exposed + melatonin treated group (EMF + Mel); EMF exposed + omega-3 (ω3) treated group (EMF + ω3); and control group (Cont). The 12-weeks-old rats were exposed to 900 MHz EMF for 60 min/day (4:00-5:00 p.m.) for 15 days. Stereological, biochemical and electrophysiological techniques were applied to evaluate protective effects of Mel and ω3. Significant cell loss in the CA1 and CA2 regions of hippocampus were observed in the EMF compared to other groups (p < 0.01). In the CA3 region of the EMF + ω3, a significant cell increase was found compared to other groups (p < 0.01). Granular cell loss was observed in the dentate gyrus of the EMF compared to the Cont (p < 0.01). EMF + ω3 has more granular cells in the cerebellum than the Cont, EMF + Mel (p < 0.01). Significant Purkinje cell loss was found in the cerebellum of EMF group compared to the other (p < 0.01). EMF + Mel and EMF + ω3 showed the same protection compared to the Cont (p > 0.05). The passive avoidance test showed that entrance latency into the dark compartment was significantly shorter in the EMF (p < 0.05). Additionally, EMF had a higher serum enzyme activity than the other groups (p < 0.01). In conclusion, our analyses confirm that EMF may lead to cellular damage in the hippocampus and the cerebellum, and that Mel and ω3 may have neuroprotective effects.

Postlaminectomy Bone and Scar Formations in Presence of Ankaferd Blood Stopper and Bitter Melon (Momordica Charantia): An Experimental Study.

AIM: A quantitative model of postlaminectomy was designed in rats. The effects of Momordica Charantia (MC) and Ankaferd blood stopper (ABS) on the bone and scar formation after laminectomy were concurrently evaluated. MATERIAL AND METHODS: Eighteen adult Wistar albino rats underwent lumbar laminectomy at L2-L3 vertebral levels, and were randomly assigned to one of three groups of six rats each. The Treatment group received MC and ABS treatment and the Control group was left untreated. Rats were sacrificed 4 weeks after treatment. Then; the lumbar spine was excised en-block, fixed and decalcified. Sections were stained with hematoxylin and eosin (H&E) and Masson"s trichrome, and evaluated for peridural fibrosis (PF), new bone formation, and vascular proliferation. RESULTS: Total volume of new bone in the MC group was significantly increased in comparison to the Control group (p < 0.05). Also; there was highly significant increase in terms of the total volume of fibrous tissue in the MC and ABS groups when compared with the Control group (p < 0.01). Besides; there was a highly significant difference between the MC and the Control groups (p < 0.01) in point of total volume of vessel. CONCLUSION: Both MC and ABS are not convenient to prevent the PF formation and MC may promote new bone formation and angiogenesis after lumbar laminectomy in rats.