Comparative anticonvulsant efficacy in the corneal kindled mouse model of partial epilepsy: Correlation with other seizure and epilepsy models

Rowley, Nicole M.; White, H. Steve

doi:10.1016/j.eplepsyres.2010.09.002

Cited by 102 publications

(132 citation statements)

References 15 publications

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“…1. Twice-daily doses of VPA (200 mg/kg) and CBZ (20 mg/kg) were based on the ED 50 of these drugs in male mice in the maximal electroshock seizure test (Bialer et al, 2004;Rowley and White, 2010). For reference, a correlative analysis between mouse maximal electroshock ED 50 values and human steady state plasma levels has previously been described (Bialer et al, 2004).…”

Section: Methodsmentioning

confidence: 99%

“…There was no further drug administration (VEH or ASD) after 7 DPI. Animals were tested 15 DPI, 8 days after the last administration of VEH or ASD, for their ability to maintain balance on a rotating rod (6 rpm) for 1 minute over three consecutive trials, as previously described (Dunham and Miya, 1957;Rowley and White, 2010;Umpierre et al, 2014). The average latency (seconds) to fall off the rotarod was calculated from the three trials, with the group means calculated for each study under investigation.…”

Section: Methodsmentioning

confidence: 99%

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Evaluating an Etiologically Relevant Platform for Therapy Development for Temporal Lobe Epilepsy: Effects of Carbamazepine and Valproic Acid on Acute Seizures and Chronic Behavioral Comorbidities in the Theiler’s Murine Encephalomyelitis Virus Mouse Model

Barker‐Haliski

Dahle

Heck

et al. 2015

J Pharmacol Exp Ther

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Central nervous system infections can underlie the development of epilepsy, and Theiler's murine encephalomyelitis virus (TMEV) infection in C57BL/6J mice provides a novel model of infectioninduced epilepsy. Approximately 50-65% of infected mice develop acute, handling-induced seizures during the infection. Brains display acute neuropathology, and a high number of mice develop spontaneous, recurrent seizures and behavioral comorbidities weeks later. This study characterized the utility of this model for drug testing by assessing whether antiseizure drug treatment during the acute infection period attenuates handlinginduced seizures, and whether such treatment modifies associated comorbidities. Male C57BL/6J mice infected with TMEV received twice-daily valproic acid (VPA; 200 mg/kg), carbamazepine (CBZ; 20 mg/kg), or vehicle during the infection (days 0-7). Mice were assessed twice daily during the infection period for handling-induced seizures. Relative to vehicle-treated mice, more CBZ-treated mice presented with acute seizures; VPA conferred no change. In mice displaying seizures, VPA, but not CBZ, reduced seizure burden. Animals were then randomly assigned to acute and long-term follow-up. VPA was associated with significant elevations in acute (day 8) glial fibrillary acidic protein (astrocytes) immunoreactivity, but did not affect NeuN (neurons) immunoreactivity. Additionally, VPA-treated mice showed improved motor performance 15 days postinfection (DPI). At 36 DPI, CBZ-treated mice traveled significantly less distance through the center of an open field, indicative of anxiety-like behavior. CBZ-treated mice also presented with significant astrogliosis 36 DPI. Neither CBZ nor VPA prevented long-term reductions in NeuN immunoreactivity. The TMEV model thus provides an etiologically relevant platform to evaluate potential treatments for acute seizures and disease modification.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Evaluating an Etiologically Relevant Platform for Therapy Development for Temporal Lobe Epilepsy: Effects of Carbamazepine and Valproic Acid on Acute Seizures and Chronic Behavioral Comorbidities in the Theiler’s Murine Encephalomyelitis Virus Mouse Model

Barker‐Haliski

Dahle

Heck

et al. 2015

J Pharmacol Exp Ther

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“…infusion of PTZ is the most sensitive model for determining seizure threshold. Kindling, an experimental model for temporal lobe epilepsy, is defined by progressive increases in electrographic and behavioral seizures (11). It is commonly caused by repeated application of subconvulsive electrical stimulation via corneal electrodes.…”

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confidence: 99%

“…Here, we examined the acute effects of cefepime and meropenem on the susceptibility of mice to seizures induced by either pentylenetetrazol (PTZ) (10) or corneal stimulation using lowcurrent electroconvulsive shocks (11). The most popular and widely used animal seizure model is the traditional PTZ test.…”

mentioning

confidence: 99%

Convulsive Liability of Cefepime and Meropenem in Normal and Corneal Kindled Mice

Tanaka

Takechi

Watanabe

et al. 2014

Antimicrob Agents Chemother

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bWe have reported significantly higher convulsion prevalence in patients treated with cefepime than in those treated with meropenem. Additionally, cefepime-associated convulsions were found only in patients with brain disorders, not renal failure. Here, we compared the convulsive liability of cefepime and meropenem administered intravenously in normal and corneal kindled mice with low seizure thresholds. We used the proconvulsive test in normal mice following pentylenetetrazol (PTZ) injection and electroconvulsive shock at low-stimulus currents and in corneal kindled mice. We also measured electroencephalogram (EEG) activity 1 min after antibiotic injections. Intravenous injection of cefepime and meropenem at 250 or 500 mg/kg of body weight had no effect on PTZ-induced convulsions in normal mice. However, in convulsions induced by electroconvulsive shock at low-stimulus currents, mean seizure stage following cefepime administration at 500 mg/kg was significantly higher than that following saline injection. Additionally, EEG spikes were recorded for mice that were given cefepime (500 mg/kg). In corneal kindled mice following cefepime injection, mean seizure stage was significantly higher than that following meropenem injection. The convulsive liability of cefepime is significantly higher than that of meropenem in normal and corneal kindled mice. In patients with low seizure thresholds, convulsive liability of cefepime may be assumed.

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“…Nowadays, the two fundamental tests enable to examine initially an anticonvulsant activity: the maximal electroshock (MES) test -model of tonic-clonic seizures in humans, and subcutaneous pentylenetetrazole (scPTZ) testmodel of absence epilepsy 21,22 . It should be noticed that in spite of significant advances that have been made in epilepsy research during last years, the MES and scPTZ screens are still recognized as the ''gold standards'' in the early stages of testing of new anticonvulsants.…”

Section: Pharmacologymentioning

confidence: 99%

Synthesis and anticonvulsant activity of new N-mannich bases derived from benzhydryl- and isopropyl-pyrrolidine-2,5-dione

Rybka

Obniska

Rapacz

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Synthesis and anticonvulsant properties of 26 new N-Mannich bases of 3-benzhydryl-(5-17) and 3-isopropyl-pyrrolidine-2,5-diones (18-30) have been described. Initial anticonvulsant screening for these compounds was evaluated in mice after intraperitoneal administration in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizures tests. The acute neurological toxicity was determined by applying the rotorod test. The in vivo results in mice showed that the majority of 3-benzhydryl-pyrrolidine-2,5-dione derivatives revealed effectiveness, while 3-isopropyl-pyrrolidine-2,5-dione derivatives were practically devoid of activity. The quantitative evaluation in both tests revealed that the most active were N-[{4-(3-chlorophenyl)-piperazin-1-yl}-methyl]-3-benzhydryl-pyrrolidine-2,5-dione (9) with ED 5 0 value ¼42.71 mg/kg (MES), ED 5 0 value4150 mg/kg (scPTZ), and N-[{4-(3-trifluoromethylphenyl)-piperazin-1-yl}-methyl]-3-benzhydryl-pyrrolidine-2,5-dione (13) with ED 5 0 value ¼101.46 mg/kg (MES) and ED 5 0 value ¼72.59 mg/kg (scPTZ). These molecules showed higher potency and lower neurotoxicity than the reference antiepileptic drugs (ethosuximide and valproic acid). To explain the probable mechanism of action of selected active derivatives (9 and 13), their influence on Na v 1.2 and L-type calcium channel was evaluated in vitro.

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Comparative anticonvulsant efficacy in the corneal kindled mouse model of partial epilepsy: Correlation with other seizure and epilepsy models

Cited by 102 publications

References 15 publications

Evaluating an Etiologically Relevant Platform for Therapy Development for Temporal Lobe Epilepsy: Effects of Carbamazepine and Valproic Acid on Acute Seizures and Chronic Behavioral Comorbidities in the Theiler’s Murine Encephalomyelitis Virus Mouse Model

Evaluating an Etiologically Relevant Platform for Therapy Development for Temporal Lobe Epilepsy: Effects of Carbamazepine and Valproic Acid on Acute Seizures and Chronic Behavioral Comorbidities in the Theiler’s Murine Encephalomyelitis Virus Mouse Model

Convulsive Liability of Cefepime and Meropenem in Normal and Corneal Kindled Mice

Synthesis and anticonvulsant activity of new N-mannich bases derived from benzhydryl- and isopropyl-pyrrolidine-2,5-dione

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