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Midazolam in a Rodent Model of Organophosphate Exposure
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May 24 2019
Source: Epilepsia. 60(7):1387-1398
Details:
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Alternative Title:Epilepsia
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Personal Author:
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Description:Objective:
Exposure to organophosphates (OPs) and OP nerve agents (NAs) causes status epilepticus (SE) and irreversible brain damage. Rapid control of seizure activity is important to minimize neuronal injury and the resulting neurological and behavioral disorders; however, early treatment will not be possible after mass release of OPs or NAs.
Methods:
We utilized a delayed-treatment model of OP exposure in adult rats by administration of diisopropyl fluorophosphate (DFP) to study the relationship between the antiseizure and neuroprotective effects of the “standard-of-care” benzodiazepine, midazolam (MDZ), when given at 30, 60, and 120 min after SE onset. After electroencephalogram (EEG) recordings, neural damage in serial brain sections was studied with Fluoro-Jade B staining.
Results:
DZ-induced seizure suppression was equivalent in magnitude regardless of treatment delay (i.e., seizure duration). When assessed globally (i.e., normalized across 10 different brain regions) for each treatment delay, MDZ administration only resulted in non-significant reductions in neuronal death. However, when data for MDZ treatment were combined from all three delay times, a small but significant reduction in global neuronal death was detected when compared to vehicle treatment, which indicated that the substantive MDZ-induced seizure suppression only led to a small reduction in neuronal death.
Significance:
In conclusion, MDZ significantly reduced DFP-induced SE intensity when treatment was delayed 30, 60, and even up to 120 min; however, this reduction in seizure intensity had no detectable effect on neuronal death at each individual delay time. These data show that although MDZ suppressed seizures, additional neuroprotective therapies are needed to mitigate the effects of OP exposure.
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Pubmed ID:31125451
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Pubmed Central ID:PMC6662604
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Document Type:
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Funding:(A120-B.P2009-2)/National Institute of Allergy and Infectious Diseases/International ; W81XWH-18-C-0181/U.S. Army Medical Research Institute of Chemical Defense/International ; W81XWH-14-C-0119/U.S. Army Medical Research Institute of Chemical Defense/International ; 27303C0140/ES/NIEHS NIH HHS/United States ; W81XWH-16-C-0140/U.S. Army Medical Research Institute of Chemical Defense/International ; ... More +
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