The Effectiveness of Ketamine as a Neuroprotective Agent After Nerve Agent Exposure

The 2013, nerve agent attacks in Syria resulted in over 1,400 deaths (including over 400 children). This demonstrates the very real danger of chemical warfare nerve agents (CWNA), which could be employed in future military-related operations or terror attacks against civilian populations. Currently, the issued MARK I kit contains prophylactic medications used to decrease the incidence of seizures after nerve agent exposure, and work to reactivate acetylicholinesterase enzyme activity impaired by agent exposure. However, there is currently no substance given to military personnel that will protect the warfighter from the long-term consequences of nerve agent exposure. Specifically, once the seizures have started, prophylactic treatment is ineffective, neurons die, and cognitive and behavioral deficits follow.

Ketamine acts as an NMDA glutamate receptor anagonist, where it potently reduces seizure activity and can reduce cellular necrosis. Findings from this research project can lend itself to the long-range goal, whichis to assess the practicality of introducing an auto injector of neuroprotective medication into the already fielded, MARK kit. Ketamin-given at dose levels that do not impair the warfighter-may serve as an effective neuroprotective agent. This study may help to ensure that military and civilian medical personnel responding to a nerve agent attack have the best countermeasures at their disposal for better force protection. The objective of this study is to evaluate the utility of Ketamine as a post-exposure treatment. to determine the utility of ketamine, two specific aims are planned.

1. Aim 1: Determine whether post-exposure administration of ketamine reduces CWNA-induced seizures, improves neurological functional outcomes, and reduces overall neuron cell death.

2. Aim 2: Determine if necrosis is the dominant pathway for neuronal death and whether or not Ketamine administration reduces brain injury. 

This research, though basic science, has the long term goal of providing nurses with an effective understanding for the treatment of CWNA-exposed victims and assist nurses with increased clinical knowledge through evidenced based research.

Final Report available on NTRL: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/PB2018100...