Temporal Expression of Neuroinflammatory Markers and Brain Injury Following Acute Soman Poisoning

Animals exposed to chemical nerve agent (i.e. soman, sarin, cyclosarin, tabun or VX) develop convulsive seizures that rapidly progress to status epilepticus and brain injury. Nerve agent-induced brain injury is caused primarily by the magnitude and duration of seizures, but inflammation may also play a role in the pathogenesis. Since a major goal of our neuroprotection program is to reduce nerve agent-induced brain damage, a more comprehensive survey of inflammatory factors in the brain is needed to accurately direct anti-inflammatory pharmacological intervention. The present study investigated the temporal expression of inflammatory mediators in the piriform cortex, correlated these findings with brain pathology and determined the anti-inflammatory therapeutic window for attenuation of neurodegeneration following acute nerve agent exposure. Male Sprague-Dawley rats were pretreated with oxime HI-6 30 min prior to soman challenge and treated with atropine methylnitrate one minute afterwards. At various time points (30 min, 1, 3, 6, 12, 24, 48 or 72 hr) after the onset of seizures, brains were processed for pathological and immunohistochemical studies or high throughput Luminex ™ multiplex immunoassay. An extensive loss of microtubule-associated protein 2 (MAP-2) was observed in the piriform cortex beginning at 12 hr after the onset of seizures. At 24 hr after onset of seizures, MAP-2 immunoreactivity was completely lost in layer three of the piriform cortex. B