Intraventricular administration of gabapentin in the rat increases flurothyl seizure threshold

Oommen, Joseph; Kraus, Alli C.; Fisher, Robert S.

doi:10.1016/j.neulet.2007.02.051

Cited by 15 publications

(11 citation statements)

References 25 publications

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“…1) as has been previously described (Ferland and Applegate, 1999, Franck, et al, 1989, Hashimoto, et al, 2006, Oommen, et al, 2007, Papandrea, et al, 2009, Samoriski and Applegate, 1997, Stafstrom, et al, 1992); however, concentrations of flurothyl necessary for generalized seizure expression are also reported (Table 1). All C57BL/6J (B6) mice tested in the repeated-flurothyl model had a high initial latency to generalized seizure expression compared to DBA/2J (D2) mice, which significantly decreased over the course of eight repeated flurothyl exposures, plateauing on seizure trial 5 (Fig.…”

Section: Resultsmentioning

confidence: 89%

Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity

et al. 2015

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Significant differences in seizure characteristics between inbred mouse strains highlight the importance of genetic predisposition to epilepsy. Here, we examined the genetic differences between the seizure-resistant C57BL/6J (B6) mouse strain and the seizure-susceptible DBA/2J (D2) strain in the phospho-Erk and Fos pathways to examine seizure-induced neuronal activity to uncover potential mechanistic correlates to these disparate seizure responsivities. Expression of neural activity markers was examined following 1, 5, or 8 seizures, or after 8 seizures, a 28 day rest period, and a final flurothyl rechallenge. Two brain regions, the hippocampus and ventromedial nucleus of the hypothalamus (VMH), had significantly different Fos expression profiles following seizures. Fos expression was highly robust in B6 hippocampus following one seizure and remained elevated following multiple seizures. Conversely, there was an absence of Fos (and phospho-Erk) expression in D2 hippocampus following one generalized seizure that increased with multiple seizures. This lack of Fos expression occurred despite intracranial electroencephalographic recordings indicating that the D2 hippocampus propagated ictal discharge during the first flurothyl seizure suggesting a dissociation of seizure discharge from Fos and phospho-Erk expression. Global transcriptional analysis confirmed a dysregulation of the c-fos pathway in D2 mice following 1 seizure. Moreover, global analysis of RNA expression differences between B6 and D2 hippocampus revealed a unique pattern of transcripts that were co-regulated with Fos in D2 hippocampus following 1 seizure. These expression differences could, in part, account for D2’s seizure susceptibility phenotype. Following 8 seizures, a 28 day rest period, and a final flurothyl rechallenge, ~85% of B6 mice develop a more complex seizure phenotype consisting of a clonic-forebrain seizure that uninterruptedly progresses into a brainstem seizure. This seizure phenotype in B6 mice is highly correlated with bilateral Fos expression in the VMH and was not observed in D2 mice, which always express clonic-forebrain seizures upon flurothyl retest. Overall, these results illustrate specific differences in protein and RNA expression in different inbred strains following seizures that precede the reorganizational events that affect seizure susceptibility and changes in seizure semiology over time.

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Section: Resultsmentioning

confidence: 89%

Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity

et al. 2015

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“…20 min later, PTZ (90 mg/kg, i.p.) was administered, then rats were placed individually in plexiglas boxes (30 9 30 9 40 cm) and observed for a period of 30 min and the latency (seconds) to the first generalized tonic-clonic seizure (GTCS) was measured [14,15].…”

Section: Methodsmentioning

confidence: 99%

“…injection of various doses of PTZ to groups of 10 animals. The animals were then observed for 30 min after injection and the latency (seconds) to the first generalized tonic-clonic seizure was measured [14,15] and the dose inducing this type of seizure in 97% of the animals (CD 97 ) was calculated in rats (90 mg/kg) according to the method of Litchfield and Wilcoxon [16].…”

Section: Ptz-induced Seizure Testmentioning

confidence: 99%

Modulation of Anticonvulsant Effects of Cannabinoid Compounds by GABA-A Receptor Agonist in Acute Pentylenetetrazole Model of Seizure in Rat

et al. 2011

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Cannabinoid system plays an important role in controlling neuronal excitability and brain function. On the other hand, modulation of gamma-aminobutyric acid (GABA) transmission is one of the initial strategies for the treatment of seizure. The aim of the present study was to evaluate possible interaction between cannabinoidergic and GABAergic systems in pentylenetetrazole (PTZ)-induced acute seizure in rat. Drugs were administered by intracerebroventricular (i.c.v.) administration 20 min before a single intraperitoneal (i.p.) injection of PTZ and the latency to the first generalized tonic-clonic seizure was measured. Both the cannabinoid receptor agonist WIN55212-2 (10, 30, 50 and 100 μg/rat) and the GABA-A receptor agonist isoguvacine (IGN; 10, 30 and 50 μg/rat) significantly increased the latency of seizure occurrence. Moreover, the fatty acid amide hydrolase inhibitor URB597 showed no anticonvulsive effect while the monoacyl glycerol lipase (MAGL) inhibitor URB602 (10, 50 and 100 μg/rat) protected rats against PTZ-induced seizure. Moreover, co-administration of IGN and cannabinoid compounds attenuated the anticonvulsant action of both WIN55212-2 and IGN in this model of seizure. Our data suggests that exogenous cannabinoid WIN55212-2 and MAGL inhibitor URB602 imply their antiseizure action in part through common brain receptorial system. Moreover, the antagonistic interaction of cannabinoids and IGN in protection against PTZ-induced seizure could suggest the involvement of GABAergic system in their anticonvulsant action.

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“…On the fifth day of infusion, the dye had spread to both hemispheres of the brain, but was localized mainly in the periventricular white matter and the ipsilateral cortex. Gabapentin concentrations in the blood were less than 1μg/mL 92. Treatment with i.c.v.…”

Section: Introductionmentioning

confidence: 91%

“…delivery was conducted by delivery of gabapentin or saline continuously to the ventricles for 5 days with a bilateral osmotic pump; the effectiveness of this approach was assessed by its ability to suppress flurothyl-induced seizures in rats. 92 Methylene blue dye was added to the saline solution to visualize the approximate fluid volume of distribution. On the fifth day of infusion, the dye had spread to both hemispheres of the brain, but was localized mainly in the periventricular white matter and the ipsilateral cortex.…”

Section: Introductionmentioning

confidence: 99%

Nanotechnology for Delivery of Drugs to the Brain for Epilepsy

2009

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Epilepsy results from aberrant electrical activity that can affect either a focal area or the entire brain. In treating epilepsy with drugs, the aim is to decrease seizure frequency and severity while minimizing toxicity to the brain and other tissues. Antiepileptic drugs (AEDs) are usually administered by oral and intravenous (IV) routes, but these drug treatments are not always effective. Drug access to the brain is severely limited by a number of biological factors, particularly the blood-brain barrier (BBB), which impedes the ability of AEDs to enter and remain in the brain. To improve the efficacy of AEDs, new drug delivery strategies are being developed; these methods fall into the three main categories: drug modification, BBB modification, and direct drug delivery. Recently, all three methods have been improved through the use of drug-loaded nanoparticles.

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Intraventricular administration of gabapentin in the rat increases flurothyl seizure threshold

Cited by 15 publications

References 25 publications

Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity

Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity

Modulation of Anticonvulsant Effects of Cannabinoid Compounds by GABA-A Receptor Agonist in Acute Pentylenetetrazole Model of Seizure in Rat

Nanotechnology for Delivery of Drugs to the Brain for Epilepsy

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