Comparison of neuropathology in rats following status epilepticus induced by diisopropylfluorophosphate and soman.

Abstract The increasing number of cases involving the use of nerve agents as deadly weapons has spurred investigation into the molecular mechanisms underlying nerve agent-induced pathology. The highly toxic nature of nerve agents restrict their use in academic research laboratories. Less toxic organophosphorus (OP) based agents including diisopropylfluorophosphate (DFP) are used as surrogates in academic research laboratories to mimic nerve agent poisoning. However, neuropathology resulting from DFP-induced status epilepticus (SE) has not been compared directly to neuropathology observed following nerve agent poisoning in the same study. Here, the hypothesis that neuropathology measured four days after SE is the same for rats exposed to DFP and soman was tested. Adult Sprague-Dawley rats were injected with soman or DFP to induce SE. Cortical electroencephalography (EEG) was recorded prior to and during soman-induced SE. EEG power analysis of rats administered soman revealed prolonged electrographic SE similar to that of rats that endure uninterrupted SE following injection of DFP. Rats that experienced soman-induced SE displayed less hippocampal neuroinflammation and gliosis compared to rats administered DFP. Seizure-induced weight change, blood-brain barrier (BBB) leakiness and neurodegeneration in most seizure sensitive limbic brain regions were similar for rats that endured SE following soman or DFP. The amalgamated pathology score calculated by combining pathological measures (weight loss, hippocampal neuroinflammation, gliosis, BBB integrity and neurodegeneration) was similar in rats administered the OP agents. These findings support use of the rat DFP model of SE as a suitable surrogate for investigating some, but not all delayed consequences produced by nerve agents.