McDonough J H, Dochterman L W, Smith C D, Shih T M
Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425, USA.
Neurotoxicology. 1995 Spring;16(1):123-32.
Brain and cardiac tissue was examined for pathological changes from rats that survived 24 hrs following exposure to a convulsant dose of the nerve agent soman. The animals had been treated following varying durations of seizure activity (2.5 - 40 min) with a number of different compounds that did or did not terminate the seizure. Moderate to severe neuropathology was evident in virtually all animals (98%) in which drug treatment did not terminate seizures. All animals that experienced up to 10 min of seizure activity before drug treatment successfully terminated the seizure were free of neuropathology. There was an increasing frequency in the incidence of neuropathology in animals that experienced 20 (10%) or 40 min (79%) of seizure activity before drug treatment terminated the seizure, but the degree of neuropathology in these groups was significantly less than that observed in animals where seizure activity was not terminated. Cardiac lesions occurred at a much higher frequency (88%) than neuropathological changes (57%) and were not consistently associated with the anticonvulsant effectiveness. Early treatment (< or = 10 min) with anticholinergic drugs, however, was associated with protection from cardiac damage. The results strongly support the hypothesis that nerve agent-induced brain damage is linked to epileptiform activity. The minimal amount of seizure activity necessary for irreversible neural damage to become evident under these conditions is approximately 20 min, and the process accelerates greatly after this minimal time has elapsed. Successful termination of seizure activity, regardless of the type of drug used, protected either totally or relatively against brain damage depending upon how long the seizure had progressed. The mechanisms responsible for cardiac lesion formation occur more rapidly and may have a cholinergic component.
对暴露于惊厥剂量的神经毒剂梭曼后存活24小时的大鼠的脑和心脏组织进行了病理变化检查。这些动物在不同时长的癫痫发作活动（2.5 - 40分钟）后，用多种不同化合物进行了治疗，这些化合物有的能终止癫痫发作，有的则不能。在几乎所有（98%）药物治疗未能终止癫痫发作的动物中，都出现了中度至重度神经病理学变化。所有在药物治疗成功终止癫痫发作前经历长达10分钟癫痫发作活动的动物均无神经病理学变化。在药物治疗终止癫痫发作前经历20分钟（10%）或40分钟（79%）癫痫发作活动的动物中，神经病理学变化的发生率呈上升趋势，但这些组中的神经病理学程度明显低于癫痫发作活动未终止的动物。心脏病变的发生频率（88%）远高于神经病理学变化（57%），且与抗惊厥效果无一致关联。然而，抗胆碱能药物的早期治疗（≤10分钟）与预防心脏损伤有关。结果有力地支持了神经毒剂诱导的脑损伤与癫痫样活动有关的假说。在这些条件下，不可逆神经损伤明显出现所需的最小癫痫发作活动量约为20分钟，且在这段最短时间过去后，这一过程会大大加速。无论使用何种药物，成功终止癫痫发作活动都能根据癫痫发作进展的时长，完全或相对地保护动物免受脑损伤。导致心脏病变形成的机制出现得更快，可能有胆碱能成分。
