This work focused on sex differences in rats exposed to sarin. Females were found to be more sensitive to sarin toxicity (LD50 67 μg/kg) than males (88 μg/kg), showed less acute hypothermic effects than males (at 120 min post sarin, 3.1 ± 1.1 and 4.5 ± 1 °C decrease, respectively), but with a significant slower recovery over days. Females’ temperature response to the cholinergic agonist oxotremorine (0.25 mg/kg, im) was more pronounced than that of males (at 30 min, 3.13 ± 0.27 and 2.13 ± 0.19 °C decrease, respectively) and both sexes recovered within 2 h of exposure. 24 h after sarin exposure (80 μg/kg) followed 1 min later by TA treatment (TMB4 7.5 mg/kg and atropine 5 mg/kg) a 255% increase in plasma MCP-1 in males but not in females was recorded. In the brain, TIMP-1 increased 43 fold in females and 25 fold in males, compared to control rats. MCP-1 increased 8 fold in females only. TNFα increased in both sexes, but the increase in female brain was higher than that recorded in males. IL-6 increased in females but not in males. IL-1β increased in both sexes. This work clearly demonstrates significant sex modulation effects on measures of toxicity, hypothermia and inflammatory markers in brain and plasma 24 h following exposure to sarin. In general, females seem to be more sensitive to the toxicity of sarin, but may be better protected against its brain damage. In light of these and other findings, the efficacy of the various available treatments, as well as those being developed, should be evaluated in both sexes.

这项工作的重点是暴露于沙林的大鼠的性别差异。发现雌性对沙林毒性（LD50 67μg/ kg）比雄性（88μg/ kg）更敏感，表现出比雄性更低的急性低温效应（沙林毒后120分钟时，分别降低3.1±1.1和4.5±1°C），但几天内恢复明显较慢。女性对胆碱能激动剂oxotremorine（0.25 mg / kg，im）的温度反应比男性更明显（分别在30分钟时降低3.13±0.27和2.13±0.19°C），并且两性在感染后2小时内恢复接触。沙林暴露（80μg/ kg）后24小时，接着1分钟后接受TA治疗（TMB4 7.5 mg / kg和阿托品5 mg / kg），男性血浆MCP-1增加255％，而女性没有。与对照组相比，在大脑中，TIMP-1在雌性中增加了43倍，在雄性中增加了25倍。MCP-1仅在女性中增加了8倍。男女中的TNFα均升高，但女性大脑中的升高高于男性。女性中IL-6升高，但男性中IL-6却没有升高。男女中IL-1β均升高。这项工作清楚地表明，暴露于沙林后24小时，性别调节对大脑和血浆中的毒性，体温过低和炎症标记物的测量具有显着的调节作用。通常，雌性似乎对沙林的毒性更敏感，但可能会更好地保护其免受脑损伤。根据这些发现和其他发现，应评估男女均可使用的各种治疗方法以及正在开发的治疗方法的疗效。