McDonough J H, Clark T R, Slone T W, Zoeffel D, Brown K, Kim S, Smith C D
Pharmacology Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Grounds, MD 21010-5425, USA.
Neurotoxicology. 1998 Jun;19(3):381-91.
This study describes the neural structures damaged following exposure to the nerve agent soman, shows there are time-dependent differences in the extent of damage in certain structures, and relates seizure-induced increases in delta band (0-3.5 Hz) electroencephalographic (EEG) activity with severity of subsequent neuropathology. Rats, instrumented to record cortical EEG activity, were pretreated with the oxime HI-6 (125 mg/kg, i.p.) and then challenged with soman (180 ug/kg, s.c.). All animals developed continuous epileptiform seizures that lasted in excess of 4 hr. Groups of animals were perfused 1, 3, 10 or 30 days following exposure. Paraffin-embedded brains were stained with hematoxylin and eosin; thirty-four neural structures were examined and scored for neural damage. All cortical areas sustained damage, with piriform and perirhinal cortices exhibiting the most severe. Subcortical limbic areas (amygdala, amygdala-piriform transition zone, hippocampus, claustrum) and various thalamic nuclei were most consistently and severely damaged in all animals regardless of survival time. Brainstem structures, cerebellum, spinal cord, and other motor output nuclei were never damaged. It was found that some structures were rated as more severely damaged when evaluated at shorter survival times. Severity of neural damage was related to high levels of EEG delta power recorded 24 hr after exposure; power during the acute seizure or 24 hr body weight loss did not predict lesion severity. Sections between AP -0.8 to -4.8 contain cortical and subcortical structures that can be readily and reproducibly evaluated for brain damage.
本研究描述了暴露于神经毒剂梭曼后受损的神经结构，表明某些结构的损伤程度存在时间依赖性差异，并将癫痫发作引起的δ波频段（0 - 3.5赫兹）脑电图（EEG）活动增加与随后神经病理学的严重程度联系起来。给植入记录皮层脑电图活动仪器的大鼠预先注射肟HI - 6（125毫克/千克，腹腔注射），然后用梭曼（180微克/千克，皮下注射）进行攻击。所有动物均出现持续超过4小时的连续性癫痫样发作。在暴露后1、3、10或30天对动物分组进行灌注。将石蜡包埋的大脑用苏木精和伊红染色；检查34个神经结构并对神经损伤进行评分。所有皮层区域均遭受损伤，梨状皮质和嗅周皮质损伤最为严重。无论存活时间如何，所有动物的皮层下边缘区域（杏仁核、杏仁核 - 梨状过渡区、海马体、屏状核）和各种丘脑核团均最常且严重受损。脑干结构、小脑、脊髓和其他运动输出核团从未受损。结果发现，在较短存活时间进行评估时，一些结构被评为损伤更严重。神经损伤的严重程度与暴露后24小时记录的高脑电图δ波功率相关；急性癫痫发作期间或24小时体重减轻期间的功率并不能预测损伤严重程度。AP - 0.8至 - 4.8之间的切片包含可容易且可重复评估脑损伤的皮层和皮层下结构。
