Academic Journal
Combination of antiseizure medications phenobarbital, ketamine, and midazolam reduces soman‐induced epileptogenesis and brain pathology in rats
| العنوان: | Combination of antiseizure medications phenobarbital, ketamine, and midazolam reduces soman‐induced epileptogenesis and brain pathology in rats |
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| المؤلفون: | Lumley, Lucille A., Marrero‐Rosado, Brenda, Rossetti, Franco, Schultz, Caroline R., Stone, Michael F., Niquet, Jerome, Wasterlain, Claude G. |
| المساهمون: | National Institute of Neurological Disorders and Stroke |
| المصدر: | Epilepsia Open ; volume 6, issue 4, page 757-769 ; ISSN 2470-9239 2470-9239 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2021 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Objective Cholinergic‐induced status epilepticus (SE) is associated with a loss of synaptic gamma‐aminobutyric acid A receptors (GABA A R) and an increase in N‐methyl‐D‐aspartate receptors (NMDAR) and amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPAR) that may contribute to pharmacoresistance when treatment with benzodiazepine antiseizure medication is delayed. The barbiturate phenobarbital enhances inhibitory neurotransmission by binding to a specific site in the GABA A R to increase the open state of the channel, decrease neuronal excitability, and reduce glutamate‐induced currents through AMPA/kainate receptors. We hypothesized that phenobarbital as an adjunct to midazolam would augment the amelioration of soman‐induced SE and associated neuropathological changes and that further protection would be provided by the addition of an NMDAR antagonist. Methods We investigated the efficacy of combining antiseizure medications to include a benzodiazepine and a barbiturate allosteric GABA A R modulator (midazolam and phenobarbital, respectively) to correct loss of inhibition, and ketamine to reduce excitation caused by increased synaptic localization of NMDAR and AMPAR, which are NMDA‐dependent. Rats implanted with transmitters to record electroencephalographic (EEG) activity were exposed to soman and treated with atropine sulfate and HI‐6 one min after exposure and with antiseizure medication(s) 40 minutes after seizure onset. Results The triple therapy combination of phenobarbital, midazolam, and ketamine administered at 40 minutes after seizure onset effectively prevented soman‐induced epileptogenesis and reduced neurodegeneration. In addition, dual therapy with phenobarbital and midazolam or ketamine was more effective than monotherapy (midazolam or phenobarbital) in reducing cholinergic‐induced toxicity. Significance Benzodiazepine efficacy is drastically reduced with time after seizure onset and inversely related to seizure duration. To overcome pharmacoresistance in severe ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/epi4.12552 |
| الاتاحة: | http://dx.doi.org/10.1002/epi4.12552 https://onlinelibrary.wiley.com/doi/pdf/10.1002/epi4.12552 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/epi4.12552 |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.A8D598A8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/epi4.12552 |
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