Neuropathologic effects of chemical warfare agents

This chapter highlights underlying mechanisms that may mediate their effects in nervous tissues. Common nerve agents developed for chemical warfare purposes include the G-series and V-series (a designation of more ambiguous origin) weapons. The G-series includes tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF); the V-series includes VX, first synthesized by the British in 1954, which is approximately an order of magnitude more potent than agents of the G-series. The neuropathologic effects of chemical warfare agents, particularly OP nerve agents, have been characterized and related to a variety of central and peripheral clinical syndromes. The most prominent of these are neuronal losses at characteristic sites in cerebrum that follow and correlate with the presence of nerve agent-induced seizure activity, with accompanying glial reaction and a subsequent, incomplete neuroregenerative response. Recent progress in the understanding of excitotoxic, neuroinflammatory, and oxidative processes that may contribute to the development of neurotoxicity provides a conceptual link to other neurologic diseases. Therapies that prove successful in preventing or treating these diseases might also be translated into neuroprotective strategies that might be useful in populations exposed to chemical warfare agents.