INTRANASAL DELIVERY OF OBIDOXIME AS A COUNTERMEASURE AGAINST CNS DAMAGE CAUSED BY NERVE AGENT POISONING

In the first phase of this project, Dr. Namboodiri and his colleagues have demonstrated that intranasal brain delivery of oximes prevents CNS damage caused by organophosphate threat agents. Exposure to organophosphate Chemical Threat Agents is a potential risk for military and civilian populations alike. Intranasal brain administration of obidoxime in an animal model of severe organophosphate poisoning can overcome limitations of the current therapeutic strategies. Studies showed that therapeutic concentrations of oximes can be delivered to almost all areas of the brain rapidly within 2.5 to 5.0 minutes. Intranasal obidoxime completely prevented mortality and neuronal loss. Fluoro-Jade-B staining revealed extensive neuronal degeneration in the surviving saline-treated animals 24 hours after paraoxon administration, whereas no detectable degenerating neurons were observed in animals given intranasal obidoxime 30 min before or 5 min after paraoxon administration. These discoveries may be built upon to develop a system of intranasal delivery of oximes as an effective method for protecting civilians and military personnel from brain injury before or soon after exposure to Chemical Threat Agents.

 

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