Mustafa Ayyildiz

The effect of ethanol on lipid peroxidation and glutathione level in the brain stem of rat.

The effects of ethanol consumption on the levels of lipid peroxidation (TBARS) and reduced glutathione (GSH) in the brain stem of male rats were investigated. The rats randomly divided into eight groups: control, 10%, 25%, 35% ethanol-consuming groups and four groups given vitamin E. Brain stem GSH levels were significantly decreased by 39.74%, 61.57%, 78.23% in rats consuming 10%, 25% and 35% ethanol, respectively. The level of TBARS was increased six-fold, 12-fold and 17-fold in these groups when compared with the control group. The administration of vitamin E (100 mg/kg/day, i.p) to ethanol-consuming rats for 20 days caused a significant increase in glutathione levels and a significant decrease in lipid peroxidation.

Evidence that sodium nitroprusside possesses anticonvulsant effects mediated through nitric oxide.

The effect of sodium nitroprusside (SNP) on epileptiform activity elicited by administration of penicillin (500 units) into the somatomotor cortex was studied in anaesthetized rats. No epileptiform activity was observed after intracortical microinjection of SNP (5 and 20 nM). Microinjection of penicillin into the somatomotor cortex induced epileptiform activity in electrocorticograms (ECoG). Epileptiform discharges elicited by penicillin were significantly decreased by SNP. The effect of SNP appeared within 1 min of application and lasted for 2-5 min. The inhibitory effect of SNP on epileptiform activity could be prevented by pretreatment with methylene blue (20 nM), a soluble guanylate cyclase inhibitor. Prior injection of haemoglobin (5 microliter), a nitric oxide (NO) scavenger, prevented the anticonvulsant effect of SNP. These results suggest that NO may be an endogenous anticonvulsant substance.

The Effects of Ascorbic Acid on Penicillin-induced Epileptiform Activity in Rats

Summary:  Purpose: Epileptic seizure results from excessive discharge in a population of hyperexcitable neurons. A number of studies help to document the effects of active oxygen free radical scavengers such as α‐tocopherol or ascorbic acid (vitamin C). In the present study, we examined the effects of ascorbic acid, at the six different doses, on penicillin‐induced epileptiform activity.

The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats.

Purpose:  Several results support the conclusion that the cannabinoid system has a role in generation and cessation of epileptic seizures. The aim of this study was to evaluate the effects of intracerebroventricular AM‐251 [N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide], a CB1‐receptor antagonist, and ACEA (arachidonyl‐2‐chloroethylamide), a CB1‐receptor agonist, on penicillin‐induced epileptiform activity in rats.

The effect of leptin on penicillin-induced epileptiform activity in rats.

Leptin is an adipose tissue-derived peptide hormone, which acts as a satiety factor to reduce appetite by interactions with hypothalamic neurons. The other possible physiological functions of leptin are still unclear. In this study, we have evaluated dose-dependent effect of leptin on penicillin-induced epileptiform activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was induced by microinjection of penicillin into the left sensorymotor cortex. Thirty minutes after penicillin injection, 1, 2 or 10 microg of leptin was administrated intracerebroventricularly (i.c.v.). Leptin (1, 2 or 10 microg) alone did not significantly change the spike amplitudes in non-penicillin pretreated control animals. One or two micrograms of leptin significantly increased the frequency of epileptiform activity in the penicillin-pretreated animals. The high dose of leptin (10 microg) did not significantly change either amplitude or frequency of epileptiform activity. One microgram i.c.v. leptin was the most effective dose in changing of frequency on penicillin-induced epileptiform activity. The proconvulsant effects of leptin appeared 90 min after leptin (1 and 2 microg) injection. These data indicate that leptin increases the frequency of penicillin-induced epileptic activity. We speculate that this action of leptin might suggest that leptin may be a proconvulsant substance.

Platelet gel does not improve peripheral nerve regeneration: an electrophysiological, stereological, and electron microscopic study.

Although use of platelet gel (PG) for promoting tissue regeneration is a popular approach because of its capacity to accelerate tissue regeneration, to our knowledge, its effects on peripheral nerve have still not been elucidated. Therefore, the aim of this study was to investigate effects of PG on sciatic nerve regeneration using electrophysiology, stereology, and electron microscopy. The study was performed using five groups of rats: sham operated (Sham), collagen tube conduit (CT), collagen tube conduit plus platelet gel (CT + PG), autogenous nerve graft (ANG), and primary repair (PR) groups. Gap length for CT and CT + PG groups is 1 cm. Electrophysiology showed that nerve conduction velocity was not different among experimental groups; the amplitude of compound action potential of PR group was significantly higher than other groups. Examination of the nerves showed that Sham group not only had a larger axon diameter but also a thicker myelin sheath. A higher number of myelinated axon was found in both ANG and PR groups in comparison to Sham, CT, and CT+PG groups. There is no significant difference between morphological quantities of CT+PG and CT group. It was expected that regeneration degree of the nerve fibers of CT+PG group would be better than CT group, which was the control group permitting to disclose the presence of a positive effect of PG on nerve regeneration, but this was not the case. Therefore, our results suggest that PG does not improve axon regeneration after microsurgical reconstruction of a nerve gap by collagen tubes.

The effects of ethanol consumption on the lipid peroxidation and glutathione levels in the right and left brains of rats

The effects of ethanol consumption on the levels of lipid peroxidation and reduced glutathione (GSH) in the cerebral hemispheres of male rats were investigated. The rats were randomly divided into eight groups: control, 10%, 25%, 35% ethanol-consuming groups, and four groups given vitamin E. The level of lipid peroxidation increased 34.32% (right brain), 35.67% (left brain) in 10% ethanol-consuming rats; 32.05% (right brain), 31.81% (left brain) in 25% ethanol-consuming rats; and 33.45% (right brain), 39.72% (left brain) in 35% ethanol-consuming rats. The GSH level of the right and left brains significantly decreased: 19.39%, 19.56%; 27.58%, 29.34%; 35.34%, 33.22% in rats consuming 10%, 25%, and 35% ethanol, respectively. These effects were partly antagonized by administration of vitamin E (100 mg/kg/day i.p.) to ethanol-consuming rats for 20 days. The results suggested that the cerebral hemispheres of adult rats are susceptible to the oxidative neurotoxic effects of ethanol, which may be blocked by vitamin E

The effect of melatonin and platelet gel on sciatic nerve repair: An electrophysiological and stereological study

Nerve regeneration after surgical reconstruction is far from optimal, and thus effective strategies for improving the outcome of nerve repair are being sought. In this experiment, we verified if postoperative intraperitoneal melatonin (MLT) administration after intraoperative platelet gel application improves peripheral nerve regeneration. In adult male rats, 1‐cm long sciatic nerve defects were repaired using four different strategies: autologous nerve graft repair followed by MLT (NM, n = 5), collagen conduit repair followed by MLT (CM, n = 5), platelet gel‐enriched collagen conduit repair followed by MLT (CGM, n = 6), and platelet gel‐enriched collagen conduit (CG, n = 5) repair followed by no substance administration. Sham operated animals were used as controls (Cont, n = 5). Ninety days after surgery, the nerve regeneration outcome was comparatively assessed by means of electrophysiological and stereological analysis. Electrophysiology revealed no significant differences between the experimental and the sham control groups. Stereological analysis showed no significant differences among the experimental groups regarding axon size and myelin thickness, but the axon number was significantly lower in the CM compared to Cont and NM group. Moreover, there was no significant difference between number of axons in CG and Cont groups, between CGM and CM, and between CM and NM. Although it was observed that platelet gel have a positive effect on nerve regeneration, but a combination of local platelet gel with MLT does not have the same effect on nerve repair.

The involvement of nitric oxide in the anticonvulsant effects of α-tocopherol on penicillin-induced epileptiform activity in rats

A variety of animal seizure models exist which help to document the effects of alpha-tocopherol (Vitamin E) and specify its action. In the present study, we provide further evidence for the functional involvement of NO in the anticonvulsant effects of alpha-tocopherol on penicillin-induced epileptiform electrocorticographical (ECoG) activity in rats. The epileptiform ECoG activity was induced by microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, the most effective dose of alpha-tocopherol (500 mg/kg) was administrated intramuscularly (i.m.). Alpha-tocopherol decreased the frequency of penicillin-induced epileptiform ECoG activity without changing the amplitude. The effect of systemic administration of nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and NO substrates, L-arginine and sodium nitro prusside (SNP) on anticonvulsive effects of alpha-tocopherol was investigated. The administration of L-NAME (60 mg/kg, i.p.) did not influence the frequency of epileptiform ECoG activity while administration of L-arginine (500 mg/kg, i.p.) and SNP (6 mg/kg, i.p.) significantly decreased in the penicillin-treated group. The administration of L-NAME (60 mg/kg, i.p.) 10 min after alpha-tocopherol (500 mg/kg, i.m.) application reversed the anticonvulsant effects of alpha-tocopherol. The administration of L-arginine (500 mg/kg, i.p.) and SNP (6 mg/kg, i.p.) did not affect the frequency of epileptiform ECoG activity in alpha-tocopherol supplemented group. L-arginine and SNP did not provide an additional anticonvulsant effect in alpha-tocopherol supplemented group. These results support the involvement of the nitric oxide pathway in the anticonvulsant effect of alpha-tocopherol on the penicillin-induced epileptiform ECoG activity.

The role of nitric oxide in the inhibitory effect of ghrelin against penicillin-induced epileptiform activity in rat

Ghrelin, a gastric peptide with key action on food intake, has been recently recognized as a potential antiepileptic agent. In the present study, we investigated the involvement of nitric oxide in the effect of ghrelin on penicillin-induced epileptiform activity in rat. Thirty minutes after penicillin injection, ghrelin, at doses of 0.5, 1, 2 microg, was administered intracerebroventricularly (i.c.v.). Ghrelin, at a dose of 1 microg, significantly decreased the mean frequency of epileptiform activity without changing the amplitude whereas other doses of ghrelin (0.5 and 2 microg) did not alter either the mean of frequency or amplitude of epileptiform activity. The effects of systemic administration of nitric oxide synthase (NOS) inhibitors, non-selective N(G)-nitro-l-arginine methyl ester (l-NAME), selective neuronal NOS inhibitor, 7-nitroindazole (7-NI) and NO substrate, l-arginine on the anticonvulsive effects of ghrelin were investigated. The administration of l-NAME (60 mg/kg, i.p.), 15 min before ghrelin (1microg) application, reversed the anti-epileptiform effects of ghrelin whereas 7-NI (40 mg/kg, i.p.) did not influence it. The present study provides electrophysiological evidence that the intracerebroventricular injection of ghrelin has an inhibitory effect against epileptiform activity in the penicillin model of epilepsy. The anti-epileptiform activity of ghrelin was reversed by nonspecific nitric oxide synthase inhibitor l-NAME, but not selective neuronal nitric oxide synthase inhibitor 7-NI, indicating that ghrelin requires activation of endothelial-NOS/NO route in the brain.