AUTHOR=Krishnan Jishnu K. S. , Moffett John R. , Puthillathu Narayanan , Johnson Erik A. , Namboodiri Aryan M. 

TITLE=Isoflurane-lipid emulsion injection as an anticonvulsant and neuroprotectant treatment for nerve agent exposure

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1466351

DOI=10.3389/fphar.2024.1466351

ISSN=1663-9812

ABSTRACT=We have shown that briefly inhaled isoflurane rapidly halts convulsions and protects the central nervous system (CNS) from organophosphate-induced neuronal loss when administered at 5% for 5 minutes, even as late as 1 hour after the nerve agent exposure. In the current study we investigated if an injectable form of isoflurane was as effective as inhaled isoflurane. We used a mixture of 10% isoflurane dissolved in an IV-compatible lipid-water emulsion for intravenous administration. Rats with an implanted jugular vein cannula were infused with 1000 microliters of the 10% isoflurane-lipid emulsion (ILE) mixture at a rate of 200 microliters per minute, which achieved full anesthesia lasting approximately 10 minutes. When administered 30 minutes after a highly lethal dose of the organophosphate insecticide paraoxon (POX), the short-duration administration halted convulsions permanently and prevented the great majority of neuronal loss as shown by Fluoro-Jade B staining (FJB). Our results indicate that injectable isoflurane is very effective for treating organophosphate poisoning, negating the need for vaporizer equipment and enabling intravenous therapy.