Informacja

Drogi użytkowniku, aplikacja do prawidłowego działania wymaga obsługi JavaScript. Proszę włącz obsługę JavaScript w Twojej przeglądarce.

Tytuł pozycji:

Delayed Adjunctive Treatment of Organophosphate-Induced Status Epilepticus in Rats with Phenobarbital, Memantine, or Dexmedetomidine.

Tytuł:
Delayed Adjunctive Treatment of Organophosphate-Induced Status Epilepticus in Rats with Phenobarbital, Memantine, or Dexmedetomidine.
Autorzy:
Spampanato J; Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah .
Bealer SL; Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah.
Smolik M; Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah.
Dudek FE; Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah.
Źródło:
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2020 Oct; Vol. 375 (1), pp. 59-68. Date of Electronic Publication: 2020 Sep 01.
Typ publikacji:
Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
Język:
English
Imprint Name(s):
Publication: 1999- : Bethesda, MD : American Society for Pharmacology and Experimental Therapeutics
Original Publication: Baltimore : Williams & Wilkins
MeSH Terms:
Time-to-Treatment*
Anticonvulsants/*administration & dosage
Dexmedetomidine/*administration & dosage
Isoflurophate/*poisoning
Memantine/*administration & dosage
Phenobarbital/*administration & dosage
Status Epilepticus/*drug therapy
Animals ; Anticonvulsants/therapeutic use ; Brain/drug effects ; Brain/pathology ; Cell Death/drug effects ; Dexmedetomidine/therapeutic use ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Interactions ; Electroencephalography ; Male ; Memantine/therapeutic use ; Neurons/drug effects ; Neurons/pathology ; Phenobarbital/therapeutic use ; Prohibitins ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus/chemically induced ; Status Epilepticus/pathology ; Treatment Outcome
Substance Nomenclature:
0 (Anticonvulsants)
0 (Phb protein, rat)
0 (Prohibitins)
12UHW9R67N (Isoflurophate)
67VB76HONO (Dexmedetomidine)
W8O17SJF3T (Memantine)
YQE403BP4D (Phenobarbital)
Entry Date(s):
Date Created: 20200903 Date Completed: 20201214 Latest Revision: 20211204
Update Code:
20240104
DOI:
10.1124/jpet.120.000175
PMID:
32873622
Czasopismo naukowe
Organophosphate (OP) exposure induces status epilepticus (SE), a medical emergency with high morbidity and mortality. Current standard medical countermeasures lose efficacy with time so that treatment delays, in the range of tens of minutes, result in increasingly poor outcomes. As part of the Countermeasures Against Chemical Threats Neurotherapeutics Screening Program, we previously developed a realistic model of delayed treatment of OP-induced SE using the OP diisopropyl fluorophosphate (DFP) to screen compounds for efficacy in the termination of SE and elimination of neuronal death. Male rats were implanted for electroencephalogram (EEG) recordings 7 days prior to experimentation. Rats were then exposed to DFP, and SE was induced for 60 minutes and then treated with midazolam (MDZ) plus one of three antiseizure drugs (ASDs)-phenobarbital (PHB), memantine (MEM), or dexmedetomidine (DMT)-in conjunction with antidotes. EEG was recorded for 24 hours, and brains were stained with Fluoro-Jade B for quantification of degenerating neurons. We found that PHB + MDZ induced a prolonged suppression of SE and reduced neuronal death. MEM + MDZ treatment exacerbated SE and increased mortality; however, surviving rats had fewer degenerating neurons. DMT + MDZ significantly suppressed SE with only a minimal reduction in neuronal death. These data demonstrate that delayed treatment of OP-induced SE with other ASDs, when added to MDZ, can achieve greater seizure suppression with additional reduction in degenerating neurons throughout the brain compared with MDZ alone. The effect of a drug on the severity of seizure activity did not necessarily determine the drug's effect on neuronal death under these conditions. SIGNIFICANCE STATEMENT: This study assesses the relative effectiveness of three different delayed-treatment regimens for the control of organophosphate-induced status epilepticus and reduction of subsequent neuronal death. The data demonstrate the potential for highly effective therapies despite significant treatment delay and a potential disconnect between seizure severity and neuronal death.
Competing Interests: Disclaimer: The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. Disclosures: F.E.D. has equity interest in and receives gifts (reduced cost for wireless equipment) and/or consultant fees from Epitel, Inc. and Cage Data Corporation, which are companies that make wireless recording devices. He has also received consulting fees from Neurotherapeutics Pharma, Rugen Holdings, and Neurona Therapeutics. The other authors declare no other financial interests.
(Copyright © 2020 by The Author(s).)

Ta witryna wykorzystuje pliki cookies do przechowywania informacji na Twoim komputerze. Pliki cookies stosujemy w celu świadczenia usług na najwyższym poziomie, w tym w sposób dostosowany do indywidualnych potrzeb. Korzystanie z witryny bez zmiany ustawień dotyczących cookies oznacza, że będą one zamieszczane w Twoim komputerze. W każdym momencie możesz dokonać zmiany ustawień dotyczących cookies