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Introduction: The effects of edaravone against pentylenetetrazole (PTZ)-induced epilepsy in male albino rats were investigated. Edaravone is a well-known commercial drug used in the treatment of strokes and amyotrophic lateral sclerosis (ALS). Antioxidant and free radical scavenging activities of edaravone have been reported in patients with ALS., Methods: In this study, the experimental groups were as follows: sham, control, 5 mg/kg edaravone, and 10 mg/kg edaravone. Behavioral assessment, determination of biochemical markers, apoptosis, nitric oxide (NO), and mRNA and protein expression of cyclooxygenase-II (COX-II) were carried out. Seizure incidence, including generalized tonic-clonic seizure (GTCS) and minimal clonic seizure (MCS), was directly associated with PTZ administration in rats., Results: Edaravone supplementation substantially increased MCS and GTCS latency in rats, and biochemical markers were significantly altered in the brain tissue of PTZ-treated rats. Edaravone treatment normalized altered biochemical markers compared with the untreated control. Apoptosis and NO levels were significantly reduced by more than 50% compared to their respective controls. COX-II mRNA was increased by 130% in PTZ-treated rats, while edaravone supplementation reduced mRNA and protein expression of COX-II by more than 20% and 40%, respectively. Immunohistochemistry indicated that COX-II protein expression was reduced by 13.2% and 33.7% following supplementation with 5 and 10 mg/kg edaravone, respectively., Conclusion: Taken together, our results suggest that edaravone functions by downregulating the levels of COX-II and NO and is a potential candidate for the treatment of PTZ-induced epilepsy., (© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Purpose: Lamotrigine (LTG) is a broad-spectrum antiepileptic drug that is widely used in clinic. However, the effect of LTG on cognition and neurodegeneration during epilepsy treatment remains controversial. In this study, we compared the cognitive effects of LTG and sodium valproate in pentylenetetrazole (PTZ)-kindled animal model, and the dose dependency was tested for LTG., Methods: PTZ-kindled animals were divided into the following treatment groups: control group, treated with 3.5 mL/kg of 0.9% sodium chloride; low-dose LTG group, treated with 12.5 mg/kg of LTG; middle-dose LTG group, treated with 25 mg/kg of LTG; high-dose LTG group, treated with 50 mg/kg of LTG; VPA group, treated with 300 mg/kg of VPA. The Morris Water Maze (MWM) test commenced from the 10th day of treatment. Hippocampal cell apoptosis was determined by TUNEL staining after two weeks of treatment., Results: Compared to the vehicle-treated control group, escape latency was significantly reduced in the middle- and high-dose LTG- and VPA-treated groups on the 3rd and 4th day of the MWM test (p < .05), and spatial probe frequency was significantly improved in the middle- and high-dose LTG- and VPA-treated groups (p < .05). Furthermore, the immunohistochemical score of TUNEL positive cells significantly decreased in the hippocampal CA1 region in the middle- and high-dose LTG- and VPA-treated groups (p < .05)., Conclusion: Our data suggests that LTG may ameliorate epilepsy-induced cognitive impairment and neuronal cell apoptosis during epilepsy treatment. LTG may ameliorate cognitive impairment and neuronal cell apoptosis during epilepsy treatment., (© 2016 The Authors Synapse Published by Wiley Periodicals, Inc.)

Maternal seizure has adverse effects on brain histology as well as on learning and memory ability in progeny. An enriched environment (EE) is known to promote structural changes in the brain and improve cognitive and motor deficits following a variety of brain injuries. Whether EE treatment in early postnatal periods could restore cognitive impairment induced by prenatal maternal seizure is unknown. Adult female Sprague-Dawley rats were randomly separated into two groups and were injected intraperitoneally either saline or pentylenetetrazol (PTZ) for 30 days. Then the fully kindled rats and control animals were allowed to mate. PTZ administration was continued until delivery, while the control group received saline at the same time. After weaning at postnatal day 22, one-half of the male offspring in the control and in the prenatal maternal group were given the environmental enrichment treatment through all the experiments until they were tested. Morris water maze testing was performed at 8 weeks of age. Western blot and synaptic ultrastructure analysis were then performed. We found that EE treatment reversed spatial learning deficits induced by prenatal maternal seizure. An EE also reversed the changes in synaptic ultrastructure following prenatal maternal seizure. In addition, prenatal maternal seizure significantly decreased phosphorylation states of cAMP response element binding (CREB) in the hippocampus, whereas EE reversed this reduced expression. These findings suggest that EE treatment on early postnatal periods could be a potential therapy for improving cognitive deficits induced by prenatal maternal seizure., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Although its effect on cognitive functions has been one of the hot topics in the present neuroscience research, the mechanism of epilepsy related cognitive impairment is not clearly revealed. Intracellular Ca(2+) plays an important role in regulating many cellular functions including learning and memory, this experiment was therefore conducted, in which, we observed the behaviors of chronic epileptic rats kindled by pentylenetetrazol (PTZ) through Morris water maze (MWM), examined the concentration of intracellular free calcium ([Ca(2+)](i)) with flow cytometry, and tested the expression of calcium/calmodulin-dependent protein kinase IIalpha (CaMKII(alpha)) and cAMP-response element binding protein (CREB) in hippocampus of those rats using western blot and reverse transcription-polymerase chain reaction (RT-PCR). The results demonstrate impaired ability of spatial learning and memory, increased concentration of [Ca(2+)](i), decreased expression levels of total CaMKII(alpha), phosphorylated CaMKII(alpha) (P-CaMKII(alpha)) and phosphorylated CREB (P-CREB) and decreased levels of CaMKII(alpha) mRNA and CREB mRNA of the epileptic rats compared with the normal control rats. Moreover, Nimodipine, an inhibitor of voltage-dependent L-type Ca(2+) channels (VDCCs), reduced the Racine's stage, improved the ability of spatial learning and memory, reversed the effect of Ca(2+) influx and expression levels of CaMKII(alpha) and CREB of the epileptic rats. We concluded that Ca(2+) influx, CaMKII(alpha) and CREB expression levels in hippocampus of chronic epileptic rats may be related with their impaired spatial learning and memory.

Objective: The changes of transcription factors CREB and glutamate receptor N-methyl-D-aspartate (NMDA) receptor subtype NR1 expressing in hippocampus and the relationship between CREB or NR1 expression change and learning or memory deficit after epilepsy. Exploring the role of CREB and NR1 in impairment of cognitive function after epilepsy., Methods: Status epilepticus (SE) and chronic epilepsy (CEP) rats were kindled by using pentylenetetrazol (PTZ) as the convulsant. The function changes of learning and memory in different types of epileptic model rats were examined by alternative electro-stimulus Y-maze test. RT-PCR detection was used to analyze NR1 and CREB mRNA expression in hippocampus tissues. Immunocytochemistry technique was used to analyze CREB protein (pCREB) expression in hippocampus tissue., Results: The results of alternative electro-stimulus Y-maze test (AESYT) showed that the total error (TE) in SE rats were higher than corresponding control rats at 1 d and 10 d after epilepsy (P < 0.05), there were no difference at 30 d after epilepsy (P > 0.05); In CEP rats, the TE in AESYT were higher than corresponding control rats at 1 d, 10 d and 30 d after epilepsy (P < 0.05). It was showed that expression of NR1 mRNA in hippocampus was significantly decreased in SE group and CEP group (P < 0.05) comparing with corresponding control group at 24 h after epilepsy, there were no significant difference between any two groups at 30 d after epilepsy (P > 0.05). The expression of CREB mRNA in hippocampus was significantly decreased in SE group (P < 0.05) at 24 h after epilepsy, and there was no significant difference in CEP group. At 30 d after epilepsy, the expression of CREB mRNA was decreased only in CEP group, but no difference in SE group. It was observed that pCREB positive neurons were distributed in CA1, CA3 and DG of rat hippocampus. The expression of pCREB positive cellular nucleus significantly decreased in SE group and CEP group comparing with control group at 24 h after epilepsy., Conclusion: The change of learning and memory after epilepsy is related to the expression of NR1 and CREB in hippocampus. The epilepsy seizures to SE and CEP rats could result in the impairment of learning and memory, and be followed by the decreases in expression of NR1 and CREB mRNA and level of CREB protein. It shows that NR1 and CREB may be involved in the pathophysiological process of learning and memory deficit.

Abstract: Mild brief hypoxia can protect against neuronal damage induced by epileptic seizures, at least in part by inhibiting apoptosis. Further elucidation of the antiepileptic mechanisms and optimization of the conditioning protocols are required before this strategy can be considered for clinical intervention. In this study, we compared the effects of different hypoxic preconditioning protocols on spontaneous recurrent seizures (SRS), intracellular free calcium concentration ([Ca2+]i), and apoptosis rate following pilocarpine-induced status epilepticus (SE). Male Sprague Dawley rats were subjected to either chronic intermittent hypobaric hypoxia (CIHH) or chronic intermittent normobaric hypoxia (CINH) (both for 6h/day×28 consecutive days) prior to pilocarpine-induced SE. The possible anticonvulsant and neuroprotective effects of CIHH and CINH were compared by video monitoring of behavioral seizure activity (frequency, delay), Nissl staining and Fluoro-Jade B (FJB) staining to examine changes in the morphology of hippocampal pyramidal neurons, and flow cytometry to detect the quantification of [Ca2+]i and cell apoptosis. Both hypoxic preconditioning protocols reduced the frequency and severity of SRS, suppressed post-ictal [Ca2+]i elevations, and inhibited neuronal apoptosis in the rat hippocampus compared to pilocarpine alone, but CIHH was more effective than CINH. Thus, mild hypoxic pretreatment, particularly when delivered as CIHH, may be a novel strategy for the clinical prevention and treatment of epilepsy. [Copyright &y& Elsevier]

Highlights: [•] Oxidative stress was induced in hippocampus of amygdala kindling rats. [•] Nrf2 and Nrf2-dependent gene products were significantly increased after seizure. [•] Nrf2-dependent gene products can protect the cells against oxidative damage. [•] To activate Nrf2-ARE signal pathway may be a new direction for treatment of epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Although its effect on cognitive functions has been one of the hot topics in the present neuroscience research, the mechanism of epilepsy related cognitive impairment is not clearly revealed. Intracellular Ca2+ plays an important role in regulating many cellular functions including learning and memory, this experiment was therefore conducted, in which, we observed the behaviors of chronic epileptic rats kindled by pentylenetetrazol (PTZ) through Morris water maze (MWM), examined the concentration of intracellular free calcium ([Ca2+] i ) with flow cytometry, and tested the expression of calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) and cAMP-response element binding protein (CREB) in hippocampus of those rats using western blot and reverse transcription-polymerase chain reaction (RT-PCR). The results demonstrate impaired ability of spatial learning and memory, increased concentration of [Ca2+] i , decreased expression levels of total CaMKIIα, phosphorylated CaMKIIα (P-CaMKIIα) and phosphorylated CREB (P-CREB) and decreased levels of CaMKIIα mRNA and CREB mRNA of the epileptic rats compared with the normal control rats. Moreover, Nimodipine, an inhibitor of voltage-dependent L-type Ca2+ channels (VDCCs), reduced the Racine''s stage, improved the ability of spatial learning and memory, reversed the effect of Ca2+ influx and expression levels of CaMKIIα and CREB of the epileptic rats. We concluded that Ca2+ influx, CaMKIIα and CREB expression levels in hippocampus of chronic epileptic rats may be related with their impaired spatial learning and memory. [Copyright &y& Elsevier]

Highlights: [•] Oxidative stress was induced in PTZ kindling mice. [•] Metformin attenuated the intensity of seizures during PTZ kindling. [•] Metformin ameliorated learning and memory impairment induced by epileptic seizures. [•] Metformin reduced the brain oxidative stress in PTZ kindling mice. [Copyright &y& Elsevier]