Endoplasmic reticulum stress produced by Thapsigargin affects the occurrence of spike-wave discharge by modulating unfolded protein response pathways and activating immune responses in a dose-dependent manner.

The Endoplasmic Reticulum (ER) is associated with many cellular functions, from post-transcriptional modifications to the proper folding of proteins, and disruption of these functions causes ER stress. Although the relationship between epileptic seizures and ER stress has been reported, the contribution of ER stress pathways to epileptogenesis is still unclear. This study aimed to investigate the possible effects of ER stress-related molecular pathways modulated by mild- and high-dose Thapsigargin (Tg) on absence epileptic activity, CACNA1H and immune responses in WAG/Rij rats. For this purpose, rats were divided into four groups; mild-dose (20 ng) Tg, high-dose (200 ng) Tg, saline, and DMSO and drugs administered intracerebroventriculary. EEG activity was recorded for 1 h and 24 h after drug administration following the baseline recording. In cortex and thalamus tissues, GRP78, ERp57, GAD153 protein changes (Western Blot), Eif2ak3, XBP-1, ATF6, CACNA1H mRNA expressions (RT-PCR), NF-κB and TNF-α levels (ELISA) were measured. Mild-dose-Tg administration resulted in increased spike-wave discharge (SWD) activity at the 24th hour compared to administration of saline, and high-dose-Tg and it also significantly increased the amount of GRP78 protein, the expression of Eif2ak3, XBP-1, and CACNA1H mRNA in the thalamus tissue. In contrast, high-dose-Tg administration suppressed SWD activity and significantly increased XBP-1 and ATF6 mRNA expression in the thalamus, and increased NF-κB and TNF-α levels. In conclusion, our findings indicate that Tg affects SWD occurrence by modulating the unfolded protein response pathway and activating inflammatory processes in a dose-dependent manner.

Neonatal Tactile Stimulation Downregulates Dendritic Spines in Layer V Pyramidal Neurons of the WAG/Rij Rat Somatosensory Cortex.

Objective: The aim of our study is to examine the effects of neonatal tactile stimulations on the brain structures that previously defined as the focus of epilepsy in the Wistar-Albino-Glaxo from Rijswijk (WAG/Rij) rat brain with genetic absence epilepsy. Methods: In the present research, morphology and density of dendritic spines were analyzed in layer V pyramidal neurons of the somatosensory cortex (SoCx) of WAG/Rij rats (nonstimulated control, tactile-stimulated, and maternal separated rats) and healthy Wistar (nonepileptic) rats. To achieve this, a Golgi-Cox method was used. Results: Dendritic spine number in layer V of the SoCx has been detected significantly higher in adult WAG/Rij rats at postnatal day 150 in comparison to nonepileptic adult control Wistar rats (p < 0.001). Moreover, quantitative analyses of dendrite structure in adult WAG/Rij rats showed a decrease in dendrite spine density of pyramidal neurons of SoCx which occurred in early neonatal exposure to maternal separation (MS) and tactile stimulation (TS) (p < 0.001). Conclusions: Our findings provide the first evidence that tactile stimulations during the early postnatal period have a long-term impact on dendrite structure in WAG/Rij rat's brain and demonstrate that neonatal tactile stimulation can regulate dendritic spines in layer V in pyramidal neurons of SoCx in epileptic brains.

Vasoactive intestinal peptide (VIP) conducts the neuronal activity during absence seizures: GABA seems to be the main mediator of VIP.

Absence epilepsy is classified as a childhood generalized epilepsy syndrome with distinctive electroencephalographic patterns. The Wistar Albino Glaxo originating from Rijswijk (WAG/Rij) strain is a very well validated animal model of absence epilepsy that also shows behavioral deficits. In addition to the gastrointestinal system, VIP is highly expressed throughout numerous brain regions, and it plays crucial roles as a neurotransmitter and as a neuromodulatory, neurotrophic and neuroprotective factor in both the central and peripheral nervous systems. In this study, adult WAG/Rij rats were divided into two groups (n = 10): a group that was administered VIP (25 ng/kg i.p.) every 2 days for 15 days and an age-matched control group that was administered physiological saline. Electrical brain activity and behavior (depressive- like behavior, learning and memory and anxiety) were investigated in both groups. In addition, the extracellular concentrations of GABA and glutamate and the GABA/glutamate ratio were measured by high-performance liquid chromatography in microdialysate samples collected from the somatosensorial cortex of WAG/Rij rats. Our results demonstrated that VIP treatment significantly suppressed the total duration and number of spike wave discharges in WAG/Rij rats. However, VIP had no significant effect on behavior. VIP increased the extracellular concentration of GABA and the GABA/glutamate ratio in the somatosensory cortex. In conclusion, VIP has suppressive effects on absence seizures, possibly by increasing the GABA concentration and inducing the transformation of glutamate to GABA in the somatosensory cortex of WAG/Rij rats.

Age dependent effects of Retigabine on absence seizure in WAG/Rij rats; an experimental study.

Retigabine (RTG, Ezogabine, DC23129) is the first neuronal potassium channel opener in the treatment of epilepsy and exerts its effects through the activation of neuronal KCNQ2/3 potassium channels; in higher doses, it acts also on sodium and voltage-gated calcium channels. The aim of this study was to investigate possible age-dependent therapeutic effects of RTG on spike-and-wave discharges (SWD) in an animal model of absence epilepsy using WAG/Rij rats. In this study, 6- and 12-month-old WAG/Rij rats were used. For both age categories, three sub-groups that consisted of one control group (n=7) by the administration of 20% DMSO (control) and two study groups by the administration of 5 mg/kg (n=7) and 15 mg/kg RTG (n=7) were designed. EEG electrodes were placed onto the skull of anaesthetized animals; and baseline EEG was recorded for one hour after a recovery period from surgery. Then, the pre-determined two distinct doses of RTG and 20% DMSO were administered as a solvent via intraperitoneal injections, and EEG was recorded for 3 hours. After injection, both doses of RTG increased the total SWD number and duration of SWD in the first and second hours in 12-month-old rats. These parameters were elevated compared to 6-month-old rats. Age-dependent effects of RTG were observed in SWD activity. Pro-epileptic effects in middle-aged WAG/Rij rats were demonstrated in both RTG doses. Differences in the distribution of KCNQ2/3 channels and switch of GABAergic system from inhibitory to excitatory with age might contribute to increased SWD activity in middle-aged rats.

Agmatine has beneficial effect on harmaline-induced essential tremor in rat.

Essential tremor (ET) is one of the most prevalent movement disorders and the most common cause of abnormal tremors. However, it cannot be treated efficiently with the currently available pharmacotherapy options. The pathophysiology of harmaline-induced tremor, most commonly used model of ET, involves various neurotransmitter systems including glutamate as well as ion channels. Agmatine, an endogenous neuromodulator, interacts with various glutamate receptor subtypes and ion channels, which have been associated with its' beneficial effects on several neurological disorders. The current study aims to assess the effect of agmatine on the harmaline model of ET. Two separate groups of male rats were injected either with saline or agmatine (40 mg/kg) 30 min prior to single intraperitoneal injection of harmaline (20 mg/kg). The percent duration, intensity and frequency of tremor and locomotor activity were evaluated by a custom-built tremor and locomotion analysis system. Pretreatment with agmatine reduced the percent tremor duration and intensity of tremor induced by harmaline, without affecting the tremor frequency. However, it did not affect the decreased spontaneous locomotor activity due to harmaline. This pattern of ameliorating effects of agmatine on harmaline-induced tremor provide the first evidence for being considered as a treatment option for ET.

Etanercept rescues cognitive deficits, depression-like symptoms, and spike-wave discharge incidence in WAG/Rij rat model of absence epilepsy.

Pro-inflammatory cytokines have been shown to be associated with the development of seizures in the WAG/Rij rat model of absence epilepsy. Importantly, WAG/Rij rats also exhibit cognitive deficits and depression-like behaviors. It is possible that pro-inflammatory cytokines mediate these comorbid conditions of absence epilepsy given their well-established effects on cognition and affective responses. The current study investigated the potential therapeutic effect of etanercept (tumor necrosis factor inhibitor) on cognitive impairment, depression-like behavior, and spike-wave discharges (SWDs) typically observed in the WAG/Rij rats. Eight-month-old male WAG/Rij rats and Wistar controls were tested in Morris water maze (MWM), passive avoidance (PA), forced swimming, sucrose preference, and locomotor activity tests, and electroencephalogram (EEG) recordings were taken from a separate group of WAG/Rij rats after 8 weeks of etanercept or vehicle treatment. Consistent with earlier work, WAG/Rij rats exhibited cognitive deficits and depression-like behavior. From these, the cognitive deficits and despair-like behavior were rescued by etanercept administration, which also reduced the frequency of SWDs without affecting their duration. Our results support the hypothesis that pro-inflammatory cytokines mediate the absence seizures and comorbid symptoms of absence epilepsy.

Effects of leptin, ghrelin and neuropeptide y on spike-wave discharge activity and certain biochemical parameters in WAG/Rij rats with genetic absence epilepsy.

This study aimed to evaluate the effects of leptin, ghrelin and neuropeptide-Y on the development of nonconvulsive seizure activity and their role on combating oxidative stress and cytokines produced by the systemic immune response in the WAG/Rij rat model for genetic absence epilepsy. Current study showed that all three peptides aggravated spike wave discharges activity and affected the oxidative stress in WAG/Rij rats without any significant changes in the levels of IL-1ß, IL-6 and TNF-α except leptin that only induced an increment in the concentration of IL-1ß. Our results support the modulatory role of these endogenous peptides on absence epilepsy.

Neonatal Tactile Stimulations Affect Genetic Generalized Epilepsy and Comorbid Depression-Like Behaviors.

Recent studies suggest that development of absence epilepsy and comorbid depression might be prevented by increased maternal care of the offspring, in which tactile stimulation induced by licking/grooming and non-nutritive contact seem to be crucial. In this study, we aimed to evaluate the effect of neonatal tactile stimulations (NTS) on absence epilepsy and depression-like behaviors in adulthood. Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat pups with a genetic predisposition to absence epilepsy were divided into tactile stimulation (TS) group, deep touch pressure (DTP) group, maternal separation (MS) group or control group. Between postnatal day 3 and 21, manipulations (TS, DTP, and MS) were carried out for 15 min and three times a day. Animals were submitted to locomotor activity, sucrose consumption test (SCT) and forced swimming test (FST) at five months of age. At the age of six months, the electroencephalogram (EEG) recordings were conducted in order to quantify the spike-wave discharges (SWDs), which is the hallmark of absence epilepsy. The TS and DTP groups showed less and shorter SWDs in later life in comparison to maternally separated and control rats. SWDs' number and total duration were significantly reduced in TS and DTP groups whereas mean duration of SWDs was reduced only in DTP group (p < 0.05). TS and DTP also decreased depression-like behaviors measured by SCT and FST in adult animals. In the SCT, number of approaches was significantly higher in TS and DTP groups than the maternally separated and control rats. In the FST, while the immobility latency of TS and DTP groups was significantly higher, only TS group showed significantly decreased immobility and increased swimming time. The results showed that NTS decreases both the number and length of SWDs and the depression-like behaviors in WAG/Rij rats probably by increasing arousal level and causing alterations in the level of some neurotrophic factors as well as in functions of the neural plasticity in the developing rat's brain.

The lower expression of parvalbumin in the primary somatosensory cortex of WAG/Rij rats may facilitate the occurrence of absence seizures.

Absence epilepsy (AE) is classified as a genetic generalized epilepsies. WAG/Rij strain of rats are regarded one of the most validated models of absence epilepsy. Studies point out the existence of hyperexcitable focus in somatosensory cortex of these rats, which has been attributed to the deficits in the GABAergic system. In the current study, we studied the changes of calcium binding proteins (CaBPs) in somatosensory cortex (S1) of the 2 and 8 month-old WAG/Rij rats and their age-matched Wistar Albino controls by investigating the expression levels of CaBPs (calbindin, calretinin and parvalbumin) in western blotting. Since WAG/Rij rats showed the low expression level of parvalbumin (PV) in western blots in comparison to Wistar Albino rats, we selectively investigated the number of PV positive neurons using the immunofluorescence staining method in order to confirm this decrement in the perioral region of somatosensory cortex (S1po). The most critical finding of this study was the age- independent reduction in the expression level of PV in the somatosensory cortex of epileptic rats as demonstrating western blotting. Nevertheless, no significant difference was found among numbers of PV + neuron in the S1po region by immunofluorescence staining concerning both of age and strain dependency. These results suggest that the disruption in the activity of the PV-expressing GABAergic interneurons might be involved in the generation of rather than the age-dependent increase in the SWDs in WAG/Rij rats.

Antagonism of adenosinergic system decrease SWD occurrence via an increment in thalamic NFkB and IL-6 in absence epilepsy.

Epilepsy is a major pathological condition, characterized by recurrent seizures and affecting approximately 1% of the population. Many studies have shown a relationship between epilepsy and inflammation. The adenosinergic system contributes to inflammation and epilepsy by regulating the release of neurotransmitters through its various receptors. This study investigates the effect of agonist and antagonist of adenosinergic system on seizure activity and cytokine levels in the WAG/Rij strain, a genetic animal model of absence epilepsy. The WAG/Rij rats used in our study were assigned to saline, Tween 20, adenosine, and caffeine groups. Tripolar electrodes were implanted on the skull, and EEG activities recorded for 3 h. ELISA was used to determine the NFkB, TNF-α, IL-1ß, and IL-6 levels in the cortical and thalamic brain regions, as well as the TNF-α, IL-1ß, and IL-6 levels in the blood samples. Administration of caffeine to rats resulted in a decreased SWD number at 30 and 60 min as determined by EEG recording after baseline (p < .05), and a significant increase in NFkB and IL-6 levels in the thalamic tissue (p < .05). Administration of adenosine to rats did not change seizures and cytokine levels. Our results show that an increase in thalamic IL-6 and NFkB levels may related with a decrement in absence epilepsy. This study clearly shows the contribution of adenosinergic system in absence seizure in WAG/Rij rats. These results also support the importance of the thalamus on occurrence of SWD in the thalamocortical loop.

Decreased ERp57 Expression in WAG/Rij Rats Thalamus and Cortex: Possible Correlation with Absence Epilepsy.

BACKGROUND: The role of intracellular proteins in the pathogenesis of absence epilepsy were mentioned. These proteins are thought to be related to energy generation, signal transduction, inflammation processes and membrane conductance. OBJECTIVES: The investigation of protein profile of the genetically epileptic rat brains was the main subject of this study. METHODS: For this, a 2D-gel electrophoresis based comparative proteome analysis was performed using thalamus tissue of genetic absence epileptic WAG/Rij and age matched Wistar rats. Regulated spots displaying differences in their abundance were identified using MALDI-TOF/TOF. Among the six spots (DHRS9, BR44, HINT1, CREM, SPRE and PDIA3/ERp57) the highest mascot score was attributed to ERp57 a neuroprotective/neurodegenerative system associated protein. Western Blot analyses were performed to validate changes occurring at ERp57 in thalamus and also identify changes in fronto-parietal cortex. RESULTS: Reductions in the expression levels of ERp57 were detected in the thalamic and the fronto-parietal brain regions of the WAG/Rij rats in comparison to Wistar rats. CONCLUSION: Such difference might be associated with the pathogenic mechanisms dictating the absence epilepsy. Lower levels of ERp57 may be playing an important role in the development of spontaneous seizures activity seen in the absence epileptic WAG/Rij rats strain.

The Effects of Adenosinergic Modulation on Cytokine Levels in a Pentylenetetrazole-Induced Generalized Tonic-Clonic Seizure Model.

OBJECTIVE: It has been suggested that the adenosinergic system and cytokines play a role in the pathogenesis of epilepsy. Although the role of the adenosinergic system in the modulation of seizure activity is well known, the mechanism of this modulation needs to be described in detail. We performed this study to determine the contribution of the proinflammatory cytokines to the generalized seizure activity during adenosine and caffeine treatment. METHODS: We induced generalized tonic-clonic seizures with the administration of 60 mg/kg pentylenetetrazole (PTZ) in male Wistar Albino rats. Adenosine (500 mg/kg) or caffeine (5 mg/kg) was administered before PTZ injection. We monitored seizure activity and then determined the TNF-α, IL-1ß, and IL-6 levels in the cortical and thalamic brain regions of rats by ELISA. RESULTS: Adenosine pretreatment significantly extended seizure latency (p < 0.05), but did not affect seizure duration and entry time to stage 4 seizure. Caffeine pretreatment did not change seizure latency and seizure duration. PTZ treatment did not change brain cytokine levels significantly (p > 0.05) compared to the control group. Whereas adenosine pretreatment decreased brain TNF-α, IL-1ß, and IL-6 levels significantly (p < 0.05), caffeine pretreatment reduced brain cytokine levels slightly but nonsignificantly (p > 0.05). CONCLUSION: Our results show that there is a clear relation between adenosinergic system and brain tissue cytokine levels. Our findings indicated that TNF-α, IL-1ß, and IL-6 participate in the pathogenesis of generalized seizures, and the inhibition of TNF-α, IL-1ß, and IL-6 with adenosinergic modulation may decrease seizure severity.

Changes in electroencephalographic characteristics and blood-brain barrier permeability in WAG/Rij rats with cortical dysplasia.

PURPOSE: This study investigated the effects of cortical dysplasia (CD) on electrophysiology and blood-brain barrier (BBB) permeability in WAG/Rij rats with genetic absence epilepsy. METHODS: Pregnant WAG/Rij rats were exposed to 145cGy of gamma-irradiation on embryonic day 17 to induce CD. An electroencephalogram was recorded from cortices subdurally in the offspring of the pregnant animals. Horseradish peroxidase (HRP) was used as determinant of BBB permeability. RESULTS: A massive tissue loss in the cerebral cortex was seen in WAG/Rij rats with CD (p<0.05). There was a significant decrease in the number and duration of spike-and-wave discharges (SWDs) and an increase in the frequency of SWDs in the WAG/Rij rats with CD when compared with the properties of SWDs in intact WAG/Rij rats (p<0.01). Ultrastructurally, the accumulation of HRP reaction products in the cerebral cortex and thalamus of WAG/Rij rats was significantly higher than that of control values (p<0.01). The accumulation of HRP reaction products in the cerebral cortex and thalamus regions of WAG/Rij rats with CD increased and was higher than that of the control and WAG/Rij animals (p<0.01). CONCLUSION: In our study, we showed that number and duration of SWDs decreased and SWD frequency increased in WAG/Rij rats with CD, suggesting a shift in seizure pattern. The association of these alterations with significant loss of cortical thickness and increased BBB permeability to HRP tracer may represent a causal relation of the EEG abnormalities with cerebral structural changes in these animals.

The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-Α, Il-1ß, Il-6, Fgf-2, galanin levels and oxidative stress in an experimental generalized convulsive seizure model.

The objective of this study is to examine the effects of the endogenous ligands leptin, ghrelin, and neuropeptide Y (NPY) on seizure generation, the oxidant/antioxidant balance, and cytokine levels, which are a result of immune response in a convulsive seizure model. With this goal, Wistar rats were divided into 5 groups-Group 1: Saline, Group 2: Saline+PTZ (65mg/kg), Group 3: leptin (4mg/kg)+PTZ, Group 4: ghrelin (80µg/kg)+PTZ, and Group 5: NPY (60µg/kg)+PTZ. All injections were delivered intraperitoneally, and simultaneous electroencephalography (EEG) records were obtained. Seizure activity was scored by observing seizure behavior, and the onset time, latency, and seizure duration were determined according to the EEG records. At the end of the experiments, blood samples were obtained in all groups to assess the serum TNF-α, IL-1ß, IL-6, FGF-2, galanin, nitric oxide (NOÖ¹), malondialdehyde (MDA), and glutathione (GSH) levels. The electrophysiological and biochemical findings (p<0.05) of this study show that all three peptides have anticonvulsant effects in the pentylenetetrazol (PTZ)-induced generalized tonic-clonic convulsive seizure model. The reduction of the levels of the pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 caused by leptin, ghrelin, and NPY shows that these peptides may have anti-inflammatory effects in epileptic seizures. Also, leptin significantly increases the serum levels of the endogenous anticonvulsive agent galanin. The fact that each one of these endogenous peptides reduces the levels of MDA and increases the serum levels of GSH leads to the belief that they may have protective effects against oxidative damage that is thought to play a role in the pathogenesis of epilepsy. Our study contributes to the clarification of the role of these peptides in the brain in seizure-induced oxidative stress and immune system physiology and also presents new approaches to the etiology and treatment of tendency to epileptic seizures.

Effects of gestational and lactational exposure to low dose mercury chloride (HgCl2) on behaviour, learning and hearing thresholds in WAG/Rij rats.

We investigated the effects of inorganic mercury exposure during gestational/lactational periods on the behaviour, learning and hearing functions in a total of 32, 5-week-old and 5-month-old WAG/Rij rats (equally divided into 4 groups as 5-week and 5-month control mercury exposure groups). We evaluated the rats in terms of locomotor activity (LA), the Morris-water-maze (MWM) test and the passive avoidance (PA) test to quantify learning and memory performance; we used distortion product otoacoustic emission (DPOAE) tests to evaluate hearing ability. There were no significant differences between the 5-week-old rat groups in LA, and we detected a significant difference (p < 0.05) in the HgCl2-treated group in PA, MWM and DPOAE tests compared with the control group. The HgCl2-treated 5-week-old group exhibited worse emotional memory performance in PA, worse spatial learning and memory performances in MWM. There were no significant differences between the groups of 5-month-old rats in LA, MWM or PA. However, the DPOAE tests worsened in the mid- and high-frequency hearing thresholds. The HgCl2-treated 5-month-old group exhibited the most hearing loss of all groups. Our results convey that mercury exposure in young rats may worsen learning and memory performances as well as hearing at high-frequency levels. While there was no statistically significant difference in the behavior and learning tests in adult rats, the DPOAE test produced poorer results. Early detection of effects of mercury exposure provides medicals team with an opportunity to determinate treatment regimens and mitigate ototoxicity. DPOAE test can be used in clinical and experimental research investigating heavy metal ototoxicity.

Comparative proteomic approach in rat model of absence epilepsy.

The aim of this study was to investigate cellular proteins in the pathogenesis of the genetic rat model of absence epilepsy. Protein spots were identified with peptide mass fingerprinting analysis using matrix-assisted laser desorption ionization time of flight mass spectrometry. Data were gathered from the frontoparietal cortex and thalamus of Wistar Albino Glaxo/Rij (WAG/Rij) and Wistar by using two-dimensional gel electrophoresis (2D-PAGE). Six proteins (Clathrin light chain-A protein, Transmembrane EMP24 Domain-Containing Protein, Stathmin-4, Myosin Light Chain4, Rheb, phosphoserine phosphatase) were found to be differentially expressed in the frontoparietal cortex of WAG/Rij and Wistar rats in both age groups. Another set of six proteins (Protein FAM89A and Oasl1, Gemin2, NuDEL1, Pur-beta, 3-alpha HSD) were found to be differentially expressed in the thalamus of WAG/Rij and Wistar rats. Findings from the frontoparietal cortex suggest the presence of altered serine metabolism and increased vesicular trafficking in the frontoparietal cortex of WAG/Rij rats compared with Wistar rats. These differences in the protein levels might reflect the crucial role of these proteins and related pathways in the generation of absence seizures. In the thalamic specimens, age-dependent changes in protein expression were remarkable, suggesting that this phenomenon may be a precursor or a consequence of absence seizures. Our findings further highlight the potential role of the mTOR signaling pathway in absence epilepsy.

Effects of linoleic acid on generalized convulsive and nonconvulsive epileptic seizures.

BACKGROUND/AIM: To comparatively investigate the effects of linoleic acid on convulsive and nonconvulsive epileptic seizures. MATERIALS AND METHODS: Rats were divided into 3 groups: convulsive epileptic rats receiving only pentylentetrazole (PTZ) injections (group 1), convulsive epileptic rats receiving PTZ and linoleic acid (group 2), and Wistar Albino Glaxo rats from Rijswijk with genetic absence epilepsy receiving linoleic acid (group 3). The duration and severity of convulsive activity were determined in groups in which convulsive seizures were induced by PTZ. In group 3, intravenous linoleic acid was administered after 1-h baseline electroencephalography (EEG) recordings. The EEG recordings were analyzed. RESULTS: When groups 1 and 2 were compared, the delay in onset of minor seizures and the decrease in the number of rats developing major seizures were found statistically significant. When the mean spike-wave discharge number and duration values for the rats in group 3 were compared to baseline values, a statistically significant increase was found in the 1st and 6th hours and there was no significant difference in the 24th hour. CONCLUSION: While our study shows that linoleic acid may be effective in the treatment of generalized convulsive epilepsy along with conventional antiepileptic drugs used in epilepsy treatment, it reports that linoleic acid is not appropriate in the treatment of nonconvulsive epilepsies.

The effects of vagal nerve stimulation in focal cerebral ischemia and reperfusion model.

AIM: This study aimed to investigate the effects of VNS in transient middle cerebral artery occlusion and reperfusion (MCAO/R) rat model of ischemia based on behavioral, morphological, and molecular approaches. MATERIAL AND METHODS: Wistar albino rats were divided into 3 groups: ischemia-reperfusion (I/R), I/R+VNS, and sham (for I/R). Each group was further divided into two subgroups for the assessment of neurological deficits and infarct area, or biochemical parameters related to oxidative stress. RESULTS: The infarct area and neurological scores were significantly lower in I/R+VNS group compared with the I/R group. MDA levels were significantly higher in I/R group compared to control and I/R+VNS groups in the cortical and subcortical specimens. There were also betweengroup differences in terms of GSH levels. GSH levels were higher in sham group compared with and I/R and I/R+VNS groups in cortical specimens whereas these levels for lower in I/R group compared to control and I/R+VNS groups in the subcortical specimens. SOD activity was higher in control group compared to I/R and I/R+VNS groups both in the cortical and subcortical specimens. There was no difference between I/R and I/R+VNS groups in neither cortical nor subcortical specimens. CONCLUSION: The neuroprotective and antioxidant properties of VNS suggest its efficacy as a potential anti-ischemic treatment.

Age-dependent decline in learning and memory performances of WAG/Rij rat model of absence epilepsy.

Recent clinical studies revealed emotional and cognitive impairments associated with absence epilepsy. Preclinical research with genetic models of absence epilepsy however have primarily focused on dysfunctional emotional processes and paid relatively less attention to cognitive impairment. In order to bridge this gap, we investigated age-dependent changes in learning and memory performance, anxiety-like behavior, and locomotor activity of WAG/Rij rats (a valid model of generalized absence epilepsy) using passive avoidance, Morris water maze, elevated plus maze, and locomotor activity cage. We tested 5 month-old and 13 month-old WAG/Rij rats and compared their performance to age-matched Wistar rats. Results revealed a decline in emotional and spatial memory of WAG/Rij rats compared to age-matched Wistar rats only at 13 months of age. Importantly, there were no significant differences between WAG/Rij and Wistar rats in terms of anxiety-like behavior and locomotor activity at either age. Results pointed at age-dependent learning and memory deficits in the WAG/Rij rat model of absence epilepsy.