Sarin poisoned rats display a hyper-
cholinergic activity including
hypersalivation,
tremors,
seizures and death. Here we studied the time and dose effects of
midazolam treatment following
nerve agent exposure. Rats were exposed to
sarin (1.2 LD50, 108 μg/kg, im), and treated 1 min later with TMB4 and
atropine (TA 7.5 and 5 mg/kg, im, respectively).
Midazolam was injected either at 1 min (1 mg/kg, im), or 1 h later (1 or 5 mg/kg i.m.). Cortical
seizures were monitored by electrocorticogram (ECoG). At 5 weeks, rats were assessed in a water maze task, and then their brains were extracted for biochemical analysis and histological evaluation. Results revealed a time and dose dependent effects of
midazolam treatment. Rats treated with TA only displayed acute signs of
sarin intoxication, 29% died within 24h and the ECoG showed
seizures for several hours. Animals that received
midazolam within 1 min survived with only minor clinical signs but with no biochemical, behavioral, or histological sequel. Animals that lived to receive
midazolam at 1h (87%) survived and the effects of the delayed administration were dose dependent.
Midazolam 5 mg/kg significantly counteracted the acute signs of intoxication and the impaired behavioral performance, attenuated some of the inflammatory response with no effect on morphological damage.
Midazolam 1mg/kg showed only a slight tendency to modulate the cognitive function. In addition, the delayed administration of both
midazolam doses significantly attenuated ECoG compared to TA treatment only. These results suggest that following prolonged seizure, high dose
midazolam is beneficial in counteracting adverse effects of
sarin poisoning.