Figure 1

Sarin exposure model and clinical manifestations. (A) PhysioTel^® F40-EET transmitters were implanted into male Sprague-Dawley rats to monitor EEG activity, body temperature, and gross motor activity. After a two-week recovery period, animals were challenged with 1 × LD₅₀ sarin, using saline as a vehicle. One minute post-seizure onset, animals were treated with 2 mg/kg atropine sulfate and 25 mg/kg 2-PAM (im). Thirty minutes later, animals were given 10 mg/kg diazepam (sc). Control animals received an equivalent volume of vehicle, atropine, 2-PAM, and diazepam. Drug treatments were not given to sarin-exposed non-seizure animals or their matched controls. The piriform cortex was extracted at 0.25, 1, 3, 6, and 24 h post-seizure onset, and at least three biological replicates were used per time point. (B) The EEG shows seizure activity following sarin exposure. It illustrates baseline EEG, seizure activity shortly after exposure, continued seizure activity 1 h after diazepam treatment, and subsiding seizure activity 24 h after sarin exposure. (C) The severity of toxic signs exhibited in seizing animals was significantly greater (p < 0.0001) than in controls. The graph indicates the total number of toxic signs listed in the moderate and severe categories. The control animals had an average toxic signs score of 0.08, and the seizing animals had an average score of 10.88. (D) The Ellman assay was used to measure the AChE activity for sarin-exposed seizing animals and their matched controls post-exposure. AChE activity was inhibited by 0.25 h post-seizure onset compared to control and continued to decrease over time until increasing slightly at 24 h. Statistically significant differences in AChE activity were seen at 6 h (p = 0.0007) and 24 h (p = 0.0168) post-seizure onset. The enzymatic activity at 0.25, 1, and 3 h was not significantly different, which is likely due to smaller sample sizes at 1 and 3 h.