The effects of leptin and cannabinoid CB1 receptor agonist/antagonist in cerebral tissues of epileptic rats.

OBJECTIVE: In this study, the effects of leptin, cannabinoid-1 (CB1) receptor agonist ACEA and antagonist AM251, and the interactions between leptin and CB1 receptor agonist/antagonist on oxidant and antioxidant enzymes in the cerebrum, cerebellum, and pedunculus cerebri tissue samples were investigated in the penicillin-induced epileptic model. METHODS: Male Wistar albino rats (n=56) were included in this study. In anesthetized animals, 500 IU penicillin-G potassium was injected into the cortex to induce epileptiform activity. Leptin (1 µg), ACEA (7.5 µg), AM251 (0.25 µg), and the combinations of the leptin+ACEA and leptin+AM251 were administered intracerebroventricularly (i.c.v.) after penicillin injections. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were measured in the cerebral tissue samples and plasma with the ELISA method. RESULTS: MDA levels increased, while SOD and GPx levels decreased after penicillin injection in the cerebrum and cerebellum. The efficacy of penicillin on SOD, MDA and GPx levels was further enhanced after leptin or AM251 injections. Whereas, ACEA decreased the MDA levels and increased GPx levels compared with the penicillin group. Administration of AM251+leptin did not change any oxidation parameter compared with the AM251. Furthermore, co-administration of ACEA and leptin significantly increased oxidative stress compared with the ACEA-treated group by increasing MDA and decreasing GPx levels. CONCLUSION: It was concluded that leptin reversed the effect of ACEA on oxidative stress. Co-administration of AM251 and leptin did not change oxidative stress compared with the AM251-treated group suggesting AM251 and leptin affect oxidative stress using the same pathways.

The role of HCN channels on the effects of T-type calcium channels and GABAA receptors in the absence epilepsy model of WAG/Rij rats.

In this study we used ivabradine (IVA), a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, to identify its effect on spike-wave discharges (SWDs); and aimed to determine the role of IVA on the effects of T-type calcium channel blocker NNC 55-0396, GABAA receptor agonist muscimol and antagonist bicuculline in male WAG/Rij rats. After tripolar electrodes for electrocorticogram (ECoG) recordings were placed on the WAG/Rij rats' skulls, 5, 10, and 20 mg/kg IVA were intraperitoneally administered for 7 consecutive days and ECoG recordings were obtained on days 0th, 3rd, 6th, and 7th for three hours before and after injections. While acute injection of 5, 10, and 20 mg/kg IVA did not affect the total number and the mean duration of SWDs, subacute administration (7 days) of IVA decreased the SWDs parameters 24 hours after the 7th injection. Interestingly, when IVA was administered again 24 hours after the 6th IVA injection, it increased the SWDs parameters. Western-blot analyses showed that HCN1 and HCN2 expressions decreased and HCN4 increased in the 5-month-old WAG/Rij rats compared to the 1-month-old WAG/Rij and 5-month-old native Wistar rats, while subacute IVA administration increased the levels of HCN1 and HCN2 channels, except HCN4. Subacute administration of IVA reduced the antiepileptic activity of NNC, while the proepileptic activity of muscimol and the antiepileptic activity of bicuculline were abolished. It might be suggested that subacute IVA administration reduces absence seizures by changing the HCN channel expressions in WAG/Rij rats, and this affects the T-type calcium channels and GABAA receptors.

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.

The electrophysiological and behavioral evaluation of the peptide hemopressin and cannabinoid CB1 receptor agonist and antagonist in pentylenetetrazol model of epilepsy in rats.

This study endeavoured to assess the effect of hemopressin (Hp), a nano peptide obtained from the alpha chain of hemoglobin, on chronic epileptic activity and its potential correlation with cannabinoid receptor type 1 (CB1). Male Wistar albino rats (230-260 g) were used. The kindling process was conducted by administering a sub-convulsant dose of pentylenetetrazol (PTZ) (35 mg/kg, i.p) three times a week for a maximum of 10 weeks. Tripolar electrodes and external cannula guides for intracerebroventricular (i.c.v) injections were surgically implanted in the skulls of kindled rats. On the day of the experiment, doses of Hp, AM-251, and ACEA were administered prior to the PTZ injections. Electroencephalography recordings and behavioural observations were conducted simultaneously for 30 min after the PTZ injection. The administration of Hp (0.6 µg, i.c.v) resulted in a decrease in epileptic activity. The CB1 receptor agonist ACEA (7.5 µg, i.c.v) showed an anticonvulsant effect, but the CB1 receptor antagonist AM-251 (0.5 µg, i.c.v) displayed a proconvulsant effect. The co-administration of Hp (0.6 µg, i.c.v) and ACEA (7.5 µg, i.c.v) and of Hp (0.6 µg, i.c.v) and AM-251 (0.5 µg, i.c.v) produced an anticonvulsant effect. However, when AM-251 was administered prior to Hp, it produced a proconvulsant impact that overrode Hp's intended anticonvulsant effect. Interestingly, the co-administration of Hp (0.03 µg) + AM-251 (0.125 µg) unexpectedly exhibited an anticonvulsant effect. Electrophysiological and behavioural evaluations demonstrated the anticonvulsant effect of Hp in the present model, highlighting the possibility that Hp may act as an agonist for the CB1 receptor.

THE effect of general anesthetics on genetic absence epilepsy in WAG/Rij rats.

AIM: To establish safe and straightforward anesthesia used in experiments, we examined the effect of ketamine, ketamine/xylazine, urethane, chloral hydrate, pentobarbital, isoflurane, dexmedetomidine, and dexmedetomidine/ketamine on epileptiform activity in genetic absence epilepsy (WAG\Rij) rats. MATERIALS AND METHOD: Sixty-three male WAG/Rij rats weighing (170-190 g) were used. Tripolar electrodes were inserted into the skull. After ECoG activities were recorded for each animal for 2 hours as controls, , the anesthetic substances were administered and the recording continued for another 2 hours. All the anesthetic substances were administered intraperitoneally except isoflurane, which was administered by inhalation.The PowerLab system was used for electrophysiological activity recording and analysis. RESULTS: The administration of ketamine (90 mg/kg), ketamine/xylazine (90/10 mg/kg), urethane (1.25 g/kg), chloral hydrate (175 mg/kg), pentobarbital (50-90 mg/kg), isoflurane (induction 5%, maintaining 3-4%), dexmedetomidine (0.5-1 mg/kg), and dexmedetomidine/ketamine (50/90 mg/kg), significantly decreased the total number of SWD, the total number of spikes, and the SWD duration (p < 0,05). The mean duration of SWD was not affected in pentobarbital (50-90 mg/kg), isoflurane (induction 5%, maintaining 3-4%), dexmedetomidine (0.5-1 mg/kg), and Dexmedetomidine/ketamine (50/90 mg/kg) groups (p > 0.05). Time scale showed a significant decrease in the total number of SWD in the first 20 minutes (P < 0.001) for all groups except dexmedetomidine (0.5-1 mg/kg), and dexmedetomidine/ketamine (50/90 mg/kg) groups (p > 0.05). CONCLUSION: The anesthetics we used significantly reduced the epileptiform activity immediately after the administration, except dexmedetomidine and dexmedetomidine/ketamine groups, so we recommend using dexmedetomidine and Dexmedetomidine/ketamine in electrophysiological studies accompanied by anesthetics.

Vortioxetine increases absence-like seizures in WAG/Rij rats but decreases penicillin- and pentylenetetrazole-induced seizures in Wistar rats.

AIM: Depression is the major psychiatric disorder in patients with epilepsy. Vortioxetine is a novel antidepressant drug for the treatment of major depressive disorders. In the present study, effects of vortioxetine were evaluated in different experimental epilepsy models of rats. MATERIALS AND METHODS: Fifty-six adult male Wistar rats and 28 WAG/Rij rats were divided into 12 groups of 7 rats each. Experiments were conducted with penicillin (500 IU, i.c.) and pentylenetetrazole models (50 mg/kg, intraperitoneally (i.p.)) in Wistar rats and genetic absence epileptic WAG/Rij rats. The vortioxetine (1, 5, or 10 mg/kg, i.p.) was evaluated in these three models. All groups were compared with their control groups. RESULTS: In the penicillin-induced seizure model, 1, 5, or 10 mg/kg vortioxetine administration significantly decreased mean spike frequency. In the pentylenetetrazole-induced seizure model, 1, 5, or 10 mg/kg vortioxetine demonstrated a significant dose-dependent decrease in mean spike frequency, an increase in the latency to minor and major seizures, and a decrease in total duration of major seizure and convulsion stage. In genetic absence epileptic WAG/Rij rats, 1 mg/kg vortioxetine caused no significant alteration in the number and duration of SWDs compared to the controls, while 5 and 10 mg/kg doses of vortioxetine increased the number and duration of SWDs. Amplitude of the epileptiform activity did not change in any of the experimental epilepsy models. CONCLUSION: The results of this study suggested that vortioxetine has anticonvulsant activity in penicillin- and pentylenetetrazole-induced seizure models. However, it exhibited proconvulsant activity in the absence epileptic WAG/Rij rats.

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 Role of NMDA Receptors in the Effect of Purinergic P2X7 Receptor on Spontaneous Seizure Activity in WAG/Rij Rats With Genetic Absence Epilepsy.

P2X7 receptors (P2X7Rs) are ATP sensitive cation channels and have been shown to be effective in various epilepsy models. Absence epilepsy is a type of idiopathic, generalized, non-convulsive epilepsy. Limited data exist on the role of P2X7Rs and no data has been reported regarding the interaction between P2X7Rs and glutamate receptor NMDA in absence epilepsy. Thus, this study was designed to investigate the role of P2X7 and NMDA receptors and their possible interaction in WAG/Rij rats with absence epilepsy. Permanent cannula and electrodes were placed on the skulls of the animals. After the healing period of the electrode and cannula implantation, ECoG recordings were obtained during 180 min before and after drug injections. P2X7R agonist BzATP, at doses of 50 µg and 100 µg (intracerebroventricular; i.c.v.) and antagonist A-438079, at doses of 20 µg and 40 µg (i.c.v.) were administered alone or prior to memantine (5 mg/kg, intraperitoneal; i.p.) injection. The total number (in every 20 min), the mean duration, and the amplitude of spike-wave discharges (SWDs) were calculated and compared. Rats were decapitated and the right and left hemisphere, cerebellum, and brainstem were separated for the measurements of the advanced oxidation protein product (AOPP), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), glutathione peroxide (GPx), and glutathione reductase (GR). BzATP and A-438079 did not alter measured SWDs parameters, whereas memantine reduced them, which is considered anticonvulsant. BzATP did not alter the anticonvulsant effect of memantine, while A-438079 decreased the effect of memantine. Administration of BzATP increased the levels of SOD and GR in cerebrum hemispheres. A-438079 did not alter any of the biochemical parameters. Memantine reduced the levels of MDA, GSH, and GR while increased the level of CAT in the cerebrum. Administration of BzATP before memantine abolished the effect of memantine on MDA levels. The evidence from this study suggests that P2X7Rs does not directly play a role in the formation of absence seizures. P2X7Rs agonist, reduced the antioxidant activity of memantine whereas agonist of P2X7Rs reduced the anticonvulsant action of memantine, suggesting a partial interaction between P2X7 and NMDA receptors in absence epilepsy model.

Effects of vitamin D and paricalcitol on epileptogenesis and behavioral properties of WAG/Rij rats with absence epilepsy.

AIM: Vitamin D (Vit D) has been considered as a neurosteroid and has a pivotal role in neuroprotection including epilepsy. Vit D regulator acts via a Vit D receptor (VDR). WAG/Rij rats have a genetically epileptic model of absence epilepsy with comorbidity of depression. The aim of the present study was to investigate the effect of Vit D and paricalcitol (PRC) on WAG/Rij rats. MATERIAL AND METHODS: Sixty-three male WAG/Rij rats and seven male Wistar rats were used. The effects of acute and chronic treatment with Vit D (5.000 and 60.000 IU/kg, i.p) and PRC (0.5, 5 and 10 µg/kg, i.p) on absence seizures, and related psychiatric comorbidity were investigated in WAG/Rij rats. Depression-like behavior was assayed by using the forced swimming test (FST) and; anxiety-like behavior by using the open field test (OFT). RESULTS: Acute Vit D treatments (5.000 and 60.000 IU/kg) similarly reduced the number and duration of spike-wave discharges (SWDs) and showed anxiolytic-antidepressive effect whereas there were no significant changes in other measured parameters between the daily and the bolus dose of Vit D. Acute administration of PRC (0.5, 5 and 10 µg/kg) showed anti-convulsive and anxiolytic-antidepressive effect. The dose (0.5 µg/kg) of PRC was the most effective dose. Chronic treatment was more effective than acute therapy in all parameters. CONCLUSION: The results of the present study demonstrate that Vit D and PRC have antiepileptic and anxiolytic-antidepressive effects on the absence epilepsy in WAG/Rij rats.

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.

Swimming exercise decreases the absence-like epileptic activity in WAG/Rij rats.

AIM: The aim of the present study was to evaluate the effects of long (60 min/day), moderate (30 min/day) and short (15 min/day) term daily swimming exercise programs for 90 days on durations and the spike-wave discharges (SWDs) seen in the electrocorticographic (ECoG) recordings of WAG/Rij rats with absence epilepsy. MATERIALS AND METHODS: Thirty-five adult male rats were divided into 5 groups as; Group 1: Control, Group 2: Sham (daily exposed to shallow water), Group 3: 15 min/day swimming exercise, Group 4: 30 min/day swimming exercise, Group 5: 60 min/day swimming exercise. After 90 days of swimming exercise program; ECoG recordings were taken for 2 h. Total number and cumulative length of SWDs in the recordings were used for evaluation of the seizures. RESULTS: Both of the SWD parameters were significantly decreased in all swimming exercise groups compared to control and sham groups. The moderate swimming group (30 min/day) was found the most effective exercise program considering both of the SWD parameters of absence epilepsy. CONCLUSION: The results of the present study provide electrophysiologic evidence for the role of swimming exercise on the modulation of genetic absence epilepsy seizures in WAG/Rij rats.

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.

The effect of serotonin on penicillin-induced epileptiform activity.

OBJECTIVE: This study was aimed at examining the epileptiform activity of the 5-HT2 serotonin receptor agonist and antagonist, and 5-hydroxytryptophan (5-HTP) in penicillin-induced epilepsy in albino Wistar rats. METHODS: For this purpose, 90 albino male Wistar rats were used in this study. Epileptiform activity was induced by an injection of penicillin, an agonist of GABAA receptor, (500 IU, i.c.) into the somatomotor cortex. Thirty minutes after the injection of penicillin, 2,5-dimethoxy-4-iodoamphetamine (DOI, an agonist of 5-HT2 receptor) (0.5, 1, 2 and 4 mg/kg, i.p.), methysergide, an antagonist of 5-HT2 receptor, (1, 10, 20, 50 and 100 µM, i.c.v.) and 5-HTP, precursor of 5-HT, (25, 50, 75 and 100 mg/kg, i.p.) were administered, respectively. RESULTS: DOI, at the doses of 1 and 2 mg/kg, significantly decreased penicillin-induced epileptiform activity (p < 0.05). Methysergide, at the doses of 20, 50 and 100 µM, significantly increased the mean spike frequency of penicillin-induced epileptiform activity (p < 0.05). The doses of 50, 75 and 100 mg/kg of 5-HTP decreased the mean spike frequency of penicillin-induced epileptiform activity (p < 0.05). The mean of amplitude of penicillin-induced epileptiform activity did not significantly change in any of the groups (p > 0.05). CONCLUSION: The electrophysiological data from the present study suggest that serotonin 5-HT2 receptors have an important role in controlling penicillin-induced epileptiform activity in the rat.

Interaction between urethane and cannabinoid CB1 receptor agonist and antagonist in penicillin-induced epileptiform activity.

Previous experimental studies have shown that various anesthetics alter the effects of cannabinoid agonists and antagonists on the cardiac response to different stimuli. Since no data have shown an interaction between urethane and cannabinoid signaling in epilepsy, we examined the suitability of urethane with regard to testing the effects of a cannabinoid CB1 receptor agonist and an antagonist on penicillin-induced epileptiform activity in rats. Permanent screw electrodes for electrocorticographic (ECoG) recordings, and a permanent cannula for administration of the substances to the brain ventricles, were placed into the cranium of rats. Epileptiform activity was induced by injection of penicillin through the cannula in conscious animal. The CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA; 7.5 µg) and the CB1 receptor antagonist [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide] (AM-251; 0.25 µg) were administered intracerebroventricularly 30 minutes after the penicillin application in urethane-anesthetized and conscious animals. Urethane completely eliminated spontaneous ictal events in ECoG recordings and reduced the frequency and total amount of epileptiform activity. It did not alter either the proconvulsant effects of AM-251 or the anticonvulsant effects of ACEA on penicillin-induced epileptiform activity. The electrophysiological evidence suggests that there is no possible interaction between urethane and cannabinoid CB1 receptors in this experimental model of epilepsy.

Effects of Ginkgo biloba extract on brain oxidative condition after cisplatin exposure.

PURPOSE: The purpose of this study was to evaluate the efficacy of Ginkgo biloba extract (EGb 761) on oxidative events of brain in cisplatin-administrated rats. METHODS: Rats were divided into four experimental groups: 1) control (n=6); 2) cisplatin (8 mg/kg, intraperitoneally one dose, n=6); 3) EGb 761 (100 mg/kg intraperitoneally for 15 days, n=6); and 4) cisplatin + EGb 761 (n=6). After drug administration, rats were sacrificed and brain tissues were removed. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels were evaluated in brain tissues. RESULTS: Single dose cisplatin administration significantly increased NO and GSH levels, but decreased MDA levels in brain tissue samples. EGb 761 treatment reversed the effects of cisplatin on NO and GSH levels, but did not affect the decreased MDA levels. CONCLUSION: Results of the study indicate that oxidative stress can be an important pathogenetic mechanism of cisplatin-induced neurotoxicity. EGb 761, an standardized extract of G. biloba leaves that has antioxidant properties, may improve the oxidative stress-related neurological side effects of cisplatin.

The effects of treadmill exercise on penicillin-induced epileptiform activity.

INTRODUCTION: The aim of this study was to evaluate the effects of short-, moderate- and long-duration treadmill exercise (15, 30 and 60 min) on the mean frequency and amplitude of penicillin-induced epileptiform activity in rats. MATERIAL AND METHODS: In this study, 32 rats were assigned to 15, 30, and 60 min running exercise groups and the control group, each consisting of 8 rats. According to the specified protocol, the rats were submitted to running exercises at the same hour of each day for 90 days. After the exercise program, the rats were administered (500 IU/2.5 µl) of penicillin into the left cortex by the microinjection method. An electrocorticogram (ECoG) recording was performed for 3 h using a data acquisition system. The frequency and the amplitude of the recordings were analyzed. RESULTS: Short-duration treadmill exercise (15 min) caused a decrease in the frequency of penicillin-induced epileptiform activity at 70 min after penicillin injection (p < 0.001). The mean frequency of epileptiform activity decreased at 90 min after penicillin injection in the 30 and 60 min treadmill exercise groups (p < 0.01). The mean amplitude of epileptiform activity was not changed in any of the exercise groups compared to the control (p > 0.05). CONCLUSIONS: The results of the present study demonstrate for the first time that short-, moderate- and long-duration treadmill exercises decreased the frequency of penicillin-induced epileptiform activity. These findings may contribute to improving the quality of life in epileptic patients.

Long-term ascorbic acid administration causes anticonvulsant activity during moderate and long-duration swimming exercise in experimental epilepsy.

The benefits of regular exercise on brain health are undeniable. Long-term exercise increases the production of reactive oxygen species in brain. Therefore, athletes often consume antioxidant supplements to remedy exercise-related damage and fatigue during exercise. The aim of this study is to evaluate the role of ascorbic acid in the effects of different intensities of swimming exercise on the brain susceptibility to experimental epilepsy in rats. Ascorbic acid was administered intraperitoneally (ip) during three different swimming exercise programme for 90 days (15 min, 30 min, 90 min/day). The anticonvulsant activity regarding the frequency of epileptiform activity appeared in the 80 min after 500 units intracortical penicillin injection in 30 min and 90 min/day exercise groups. The administration of ascorbic acid (100 mg/kg, ip) did not alter the anticonvulsant properties seen in the in short-duration (15 min/day) swimming exercise group. The amplitude of epileptiform activity also became significant in the 110 and 120 min after penicillin injection in the moderate (30 min/day) and long duration (60 min/day) groups, respectively. The results of the present study provide electrophysiologic evidence that long-term administration of ascorbic acid causes anticonvulsant activities in the moderate and long-duration swimming exercise. Antioxidant supplementation such as ascorbic acid might be suggested for moderate and long-duration swimming exercise in epilepsy.

The effect of hemostatic agents and tissue adhesive on injured peripheral nerve healing in rats - Part I. Electrophysiological study.

BACKGROUND: In the practice of maxillofacial surgery, bleeding and nerve injury have common problems. In the control of bleeding, hemostatic agents and tissue adhesives have been frequently used. The effect of these hemostatic agents and tissue adhesives on the injured neural tissues has not been known. OBJECTIVES: In this study, we aimed to investigate the effects of hemostatic agents and tissue adhesive on injured nerve tissues. MATERIAL AND METHODS: Forty-two rats randomly divided into seven groups: Control, Oxidized Regenerated Cellulose (ORC), Gelatine Sponge (GS), Bovine Collagen (BC), Ankaferd BloodStopper (ABS), Glutaraldehyde Surgical Adhesive (BioGlue®) and N-butil-2 cyanoacrylate (Glubran®2). The left sciatic nerves were crushed and surrounded by hemostatic agents and tissue adhesives. At the end of 12 weeks, the surgical site was reopened and electrophysiological recordings were performed. RESULTS: In the ORC, GS, and BC groups, the compound action potential (CAP) values were lower compared to the control group (p < 0.05). Although the values of CAP in the ABS group were higher than in the control group while CAP values in the BioGlue and Glubran®2 groups were lower than the control group, there was no statistical significance between the experimental and control groups (p > 0.05). In the ORC, BC, GS, and Glubran®2 groups, the nerve conduction velocities (NCV) values were lower than in the control group (p < 0.05). In the ABS and BioGlue groups, NCV values were lower compared to the control group but no significant differences were found (p > 0.05). CONCLUSIONS: The present study provides evidence that ABS is the most suitable hemostatic agent due to its favorable effect on the healing of injured neural tissues. BioGlue is also a suitable surgical agent with no adverse effects.

The interaction between ghrelin and cannabinoid systems in penicillin-induced epileptiform activity in rats.

The majority of experimental and clinical studies show that ghrelin and cannabinoids are potent inhibitors of epileptic activity in various models of epilepsy. A number of studies have attempted to understand the connection between ghrelin and cannabinoid signalling in the regulation of food intake. Since no data show a functional interaction between ghrelin and cannabinoids in epilepsy, we examined the relationship between these systems via penicillin-induced epileptiform activity in rats. Doses of the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) (2.5 and 7.5 µg), the CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide (AM-251) (0.25 and 0.5 µg) and ghrelin (0.5 and 1 µg) were administered intracerebroventricularly (i.c.v.) 30 minutes after the intracortical (i.c.) application of penicillin. In the interaction groups, the animals received either an effective dose of ACEA (7.5 µg, i.c.v.) or a non-effective dose of ACEA (2.5 µg, i.c.v.) or effective doses of AM-251 (0.25, 0.5 µg, i.c.v.) 10 minutes after ghrelin application. A 1 µg dose of ghrelin suppressed penicillin-induced epileptiform activity. The administration of a 0.25 µg dose of AM-251 increased the frequency of penicillin-induced epileptiform activity by producing status epilepticus-like activity. A 7.5 µg dose of ACEA decreased the frequency of epileptiform activity, whereas a non-effective dose of ACEA (2.5 µg) did not change it. Effective doses of AM-251 (0.25, 0.5 µg) reversed the ghrelin's anticonvulsant activity. The application of non-effective doses of ACEA (2.5 µg) together with ghrelin (0.5 µg) within 10 minutes caused anticonvulsant activity, which was reversed by the administration of AM-251 (0.25 µg). The electrophysiological evidence from this study suggests a possible interaction between ghrelin and cannabinoid CB1 receptors in the experimental model of epilepsy.

Comparison between flexible collagen and vein conduits used for size-discrepant nerve repair: an experimental study in rats.

Primary nerve repair is the gold standard in nerve reconstruction. When primary repair is not possible for injured nerves, conduit-assisted repair methods are frequently used. As conduits, autologous vein segments or allogenic biodegradable products can be used. However, their effectiveness when used in a nerve defect where a size discrepancy exists has not been compared. In this study, either a vein graft or a synthetic collagen conduit was used to bridge 10-mm defects between size-discrepant tibial and peroneal nerves in a rat model. After 90 days, nerve regeneration was evaluated using electrophysiological and histological methods. It can be concluded based on the results of this study that bridging a 10-mm nerve gap with synthetic collagen conduits and autologous vein grafts yielded similar results in small-to-large nerve coaptations, with the vein graft being slightly more effective.