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.

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.

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 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.

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.

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.

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 Effect of Chronic Swimming Exercise and Vitamin E Supplementation on Bone Element Metabolism in Epileptic Rats.

Introduction: This study aimed to investigate the effects of chronic swimming exercise and vitamin E administration on elemental levels in the bone tissue of epileptic rats. Methods: Forty-eight rats were divided into six groups: Control, Swimming, Swimming + vitamin E, Swimming + Epilepsy, Swimming + Epilepsy + vitamin E, and Epilepsy. Vitamin E was administered to the animals chronically by gavage at a dose of 500 mg/kg every other day for 3 months. Epileptiform activity was induced with penicillin in animals 24 hours after the last vitamin E intake. The exercise program consisted of daily 30-minute swimming sessions. At the end of the treatment period, the levels of calcium, chromium, copper, iron, magnesium, manganese, lead, and zinc (µg/gram tissue) in bone tissue samples were measured using an atomic emission device. Results: The results showed that all epileptic groups had significantly lower bone chromium levels compared to the control groups (p<0.05). The epileptic, and epileptic swimming groups had the lowest levels of bone calcium, magnesium, and zinc (p<0.05). Vitamin E administration resulted in a significant increase in bone calcium, magnesium, and zinc levels in the epileptic swimming group with vitamin E compared to the epileptic and epileptic swimming groups. (p<0.05). Conclusion: The findings of the study show that the administration of vitamin E improves calcium, magnesium, and zinc metabolism in the deteriorated bone tissue of the epileptic rat model.

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 interactions of nitric oxide and acetylcholine on penicillin-induced epilepsy in rats.

The aim of this study was to investigate the interaction between nitric oxide (NO) and acetylcholine (ACh) in penicillin-induced experimental epilepsy. Adult male Wistar rats weighing 220 ± 35 g were used in the experiments. The epileptiform activity was induced by microinjection of penicillin (200 IU/1 µl) into the left sensorymotor cortex. Electrocorticogram was recorded by using Ag/AgCl ball electrodes. Sodium nitroprusside (SNP), a NO donor, given intracortically 30 min after penicillin significantly reduced the spike frequency whereas ACh increased the epileptiform activity for 5 min. Atropine, an antagonist for muscarinic receptors, was given intracortically 30 min after penicillin and did not significantly affect epileptiform activity for 30 min. SNP given after atropine significantly suppressed the epileptiform activity. ACh given 10 min after Nω-nitro-L: -arginine methyl ester (L-NAME), a nonspecific nitric oxide synthase inhibitor, did not have a significant effect on spike frequency. When ACh and SNP were administered together, penicillin induced epileptiform activity and spike frequency were significantly suppressed from the 10th minute onwards. It can be concluded that ACh increases the penicillin-induced epileptiform activity while co-administration of ACh and SNP produces a potent anticonvulsant effect as compared to SNP alone.

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.

Periaqueductal grey stimulation induced panic-like behaviour is accompanied by deactivation of the deep cerebellar nuclei.

Until recently, the cerebellum was primarily considered to be a structure involved in motor behaviour. New anatomical and clinical evidence has shown that the cerebellum is also involved in higher cognitive functions and non-motor behavioural changes. Functional imaging in patients with anxiety disorders and in cholecystokinin tetrapeptide-induced panic-attacks shows activation changes in the cerebellum. Deep brain stimulation of the dorsolateral periaqueductal grey (dlPAG) and the ventromedial hypothalamus (VMH) in rats has been shown to induce escape behaviour, which mimics a panic attack in humans. We used this animal model to study the neuronal activation in the deep cerebellar nuclei (DCbN) using c-Fos immunohistochemistry. c-Fos expression in the DCbN decreased significantly after inducing escape behaviour by stimulation of the dlPAG and the VMH, indicating that the DCbN were deactivated. This study demonstrates that the DCbN are directly or indirectly involved in panic attacks. We suggest that the cerebellum plays a role in the selection of relevant information, and that deactivation of the cerebellar nuclei is required to allow inappropriate behaviour to occur, such as panic attacks.

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 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.

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. METHODS: In the first set of experiments, 30 min after penicillin injection, AM-251, at doses of 0.125, 0.25, 0.5, and 1 µg, was administered intracerebroventricularly (i.c.v.). In the second set of experiments, 30 min after penicillin injection, ACEA, at doses of 2.5, 5, 7.5, and 15 µg (i.c.v.), was administered. In the third set of experiments, AM-251, at doses of 0.125 and 0.25 µg (i.c.v.), was administered 10 min before ACEA (7.5 µg, i.c.v.) injection. RESULTS: ACEA, at a dose of 7.5 µg, significantly decreased the frequency of penicillin-induced epileptiform activity without changing the amplitude. ACEA, at doses of 2.5, 5, and 15 µg, had no impact on either frequency or amplitude of epileptiform activity. AM-251, at doses of 0.25 and 0.50 µg, significantly increased the frequency of epileptiform activity. AM-251, at a dose of 0.25 µg (i.c.v.), was the most effective in changing the frequency of penicillin-induced epileptiform activity, and it also caused status epilepticus-like activity. AM-251, at doses of 0.125 and 0.25 µg, 10 min before ACEA (7.5 µg), reversed the anticonvulsant action of ACEA. DISCUSSION: The results of the present study provide electrophysiologic evidence for the role of CB1 receptors in regulating the frequency of epileptiform activity in the model of penicillin-induced epilepsy. To elucidate the precise mechanism of cannabinoid action in the brain during seizure, more advanced electrophysiologic and neurochemical studies are required.

The effect of alpha-tocopherol in the acute ethanol intake and its withdrawal on penicillin-induced epilepsy.

The present study was designed to investigate the influence of acute ethanol intake and its withdrawal on the anticonvulsant effect of alpha-tocopherol in penicillin-induced epileptiform activity. Ethanol-treated rats received a daily dose of 3 g/kg or 9.0 g/kg of 30% ethanol solution for 3 days. Thirty minutes after penicillin injection (500 units, i.c.) the most effective dose of alpha-tocopherol (500 mg/kg) was administered intramuscularly (i.m.). Acute administration of ethanol, in a dose of 3 g/kg, did not change either frequency or amplitude of penicillin-induced epileptiform activity, while dose of 9 g/kg ethanol significantly decreased the mean frequency of penicillin-induced epileptiform ECoG activity in the ethanol-treated group. Ethanol (9 g/kg) withdrawal also caused an increase in the amplitude of epileptiform ECoG activity in the withdrawal group. The results suggest that acute administration of high dose ethanol (9 g/kg) and alpha-tocopherol have some limited anticonvulsive effects in penicillin-induced epileptiform activity in rats.

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.

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.

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.