Anticonvulsant Effects of Carbamazepine on Spontaneous Seizures in Rats with Kainate‐induced Epilepsy: Comparison of Intraperitoneal Injections with Drug‐in‐food Protocols

Grabenstatter, Heidi L.; Clark, Shawn P.; Dudek, F. Edward

doi:10.1111/j.1528-1167.2007.01263.x

Cited by 56 publications

(67 citation statements)

References 16 publications

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“…In the kainic acid model, some anti-epileptic drugs were proven effective when administered after the chemoconvulsant. For instance, a single intraperitoneal administration of topiramate or carbamazepine can reduce the frequency of spontaneous seizures but the anti-ictogenic effect is short-lasting (Grabenstatter et al, 2005(Grabenstatter et al, , 2007. The daily oral administration of carbamazepine however appears more effective since its effect is long-lasting and may even completely block seizure occurrence (Ali et al, 2012;Grabenstatter et al, 2007).…”

Section: Effect Of Anti-epileptic Drugs On Spontaneous Seizuresmentioning

confidence: 99%

“…For instance, a single intraperitoneal administration of topiramate or carbamazepine can reduce the frequency of spontaneous seizures but the anti-ictogenic effect is short-lasting (Grabenstatter et al, 2005(Grabenstatter et al, , 2007. The daily oral administration of carbamazepine however appears more effective since its effect is long-lasting and may even completely block seizure occurrence (Ali et al, 2012;Grabenstatter et al, 2007). However, it is unclear if non-convulsive seizures are also blocked since no study has been performed so far on kainic-acid treated animals implanted with depth electrodes and treated with anti-epileptic drugs for multiple consecutive days.…”

Section: Effect Of Anti-epileptic Drugs On Spontaneous Seizuresmentioning

confidence: 99%

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Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration

Lévesque

Avoli

Bernard

2016

Journal of Neuroscience Methods

210

182

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In order to understand the pathophysiology of temporal lobe epilepsy (TLE), and thus to develop new pharmacological treatments, in vivo animal models that present features similar to those seen in TLE patients have been developed during the last four decades. Some of these models are based on the systemic administration of chemoconvulsants to induce an initial precipitating injury (status epilepticus) that is followed by the appearance of recurrent seizures originating from limbic structures. In this paper we will review two chemically-induced TLE models, namely the kainic acid and pilocarpine models, which have been widely employed in basic epilepsy research. Specifically, we will take into consideration their behavioral, electroencephalographic and neuropathologic features. We will also evaluate the response of these models to anti-epileptic drugs and the impact they might have in developing new treatments for TLE.

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Section: Effect Of Anti-epileptic Drugs On Spontaneous Seizuresmentioning

confidence: 99%

Section: Effect Of Anti-epileptic Drugs On Spontaneous Seizuresmentioning

confidence: 99%

Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration

Lévesque

Avoli

Bernard

2016

Journal of Neuroscience Methods

210

182

View full text Add to dashboard Cite

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“…Rats were continuously monitored with traditional wired EEG beginning 2 months after epileptogenic kainate administration Rats were treated with either drug‐containing food or food without the drug on day 1 and then observed through day 3 32, 38. On day 4, the rats were crossed over to the other treatment (i.e., placebo if the first treatment was celecoxib), and observed through day 6.…”

Section: Resultsmentioning

confidence: 99%

“…A repeated‐measure, crossover protocol was used with 100 mg/kg/day Celecoxib in custom‐made food (Bio‐serv) 38. The 100 mg/kg/day dose of Celecoxib would be equivalent to five injections of 20 mg/kg/day 39.…”

Section: Methodsmentioning

confidence: 99%

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Staged anticonvulsant screening for chronic epilepsy

Berdichevsky

Saponjian

Park

et al. 2016

Ann Clin Transl Neurol

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ObjectiveCurrent anticonvulsant screening programs are based on seizures evoked in normal animals. One‐third of epileptic patients do not respond to the anticonvulsants discovered with these models. We evaluated a tiered program based on chronic epilepsy and spontaneous seizures, with compounds advancing from high‐throughput in vitro models to low‐throughput in vivo models.MethodsEpileptogenesis in organotypic hippocampal slice cultures was quantified by lactate production and lactate dehydrogenase release into culture media as rapid assays for seizure‐like activity and cell death, respectively. Compounds that reduced these biochemical measures were retested with in vitro electrophysiological confirmation (i.e., second stage). The third stage involved crossover testing in the kainate model of chronic epilepsy, with blinded analysis of spontaneous seizures after continuous electrographic recordings.ResultsWe screened 407 compound‐concentration combinations. The cyclooxygenase inhibitor, celecoxib, had no effect on seizures evoked in normal brain tissue but demonstrated robust antiseizure activity in all tested models of chronic epilepsy.InterpretationThe use of organotypic hippocampal cultures, where epileptogenesis occurs on a compressed time scale, and where seizure‐like activity and seizure‐induced cell death can be easily quantified with biomarker assays, allowed us to circumvent the throughput limitations of in vivo chronic epilepsy models. Ability to rapidly screen compounds in a chronic model of epilepsy allowed us to find an anticonvulsant that would be missed by screening in acute models.

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Regression of Epileptogenesis by Inhibiting Tropomyosin Kinase B Signaling following a Seizure

Krishnamurthy

Huang

Harward

et al. 2019

Annals of Neurology

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Objective Temporal lobe epilepsy (TLE) is a devastating disease in which seizures persist in 35% of patients despite optimal use of antiseizure drugs. Clinical and preclinical evidence implicates seizures themselves as one factor promoting epilepsy progression. What is the molecular consequence of a seizure that promotes progression? Evidence from preclinical studies led us to hypothesize that activation of tropomyosin kinase B (TrkB)–phospholipase‐C‐gamma‐1 (PLCγ1) signaling induced by a seizure promotes epileptogenesis. Methods To examine the effects of inhibiting TrkB signaling on epileptogenesis following an isolated seizure, we implemented a modified kindling model in which we induced a seizure through amygdala stimulation and then used either a chemical–genetic strategy or pharmacologic methods to disrupt signaling for 2 days following the seizure. The severity of a subsequent seizure was assessed by behavioral and electrographic measures. Results Transient inhibition of TrkB‐PLCγ1 signaling initiated after an isolated seizure limited progression of epileptogenesis, evidenced by the reduced severity and duration of subsequent seizures. Unexpectedly, transient inhibition of TrkB‐PLCγ1 signaling initiated following a seizure also reverted a subset of animals to an earlier state of epileptogenesis. Remarkably, inhibition of TrkB‐PLCγ1 signaling in the absence of a recent seizure did not reduce severity of subsequent seizures. Interpretation These results suggest a novel strategy for limiting progression or potentially ameliorating severity of TLE whereby transient inhibition of TrkB‐PLCγ1 signaling is initiated following a seizure. ANN NEUROL 2019;86:939–950

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Anticonvulsant Effects of Carbamazepine on Spontaneous Seizures in Rats with Kainate‐induced Epilepsy: Comparison of Intraperitoneal Injections with Drug‐in‐food Protocols

Cited by 56 publications

References 16 publications

Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration

Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration

Staged anticonvulsant screening for chronic epilepsy

Regression of Epileptogenesis by Inhibiting Tropomyosin Kinase B Signaling following a Seizure

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