DataSheet1_Isoflurane-lipid emulsion injection as an anticonvulsant and neuroprotectant treatment for nerve agent exposure.docx

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 min, even as late as 1 h after organophosphate 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 1,000 μL of the 10% isoflurane-lipid emulsion (ILE) mixture at a rate of 200 μL per minute, which achieved full anesthesia lasting approximately 10 min. When administered 30 min after a highly lethal dose of the organophosphate insecticide paraoxon (POX), the short-duration administration halted convulsions over the course of the study 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.