Disruption of the blood-brain barrier and neuronal cell death in cingulate cortex, dentate gyrus, thalamus, and hypothalamus in a rat model of Gulf-War syndrome
Disruption of the blood-brain barrier and neuronal cell death in cingulate cortex, dentate gyrus, thalamus, and hypothalamus in a rat model of Gulf-War syndrome
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DOI：
10.1006/nbdi.2002.0524
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发表时间：
2002-08-01
影响因子：
6.1
通讯作者：
Abou-Donia, MB
中科院分区：
文献类型：
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作者：
Abdel-Rahman, A;Shetty, AK;Abou-Donia, MB
我们研究了联合暴露于束缚应激和低剂量的化学品溴化吡啶斯的明（PB），N，N-二乙基-间甲苯酰胺（DEET），和氯菊酯的成年雄性大鼠，海湾战争综合征的模型的影响。动物每天暴露于以下之一，持续28天：（i）应激和化学品的组合（PB，1.3 mg/kg/天; DEET，40 mg/kg/天;和氯菊酯，0.13 mg/kg/天）;（ii）应激和媒介物;（iii）单独的化学品;和（iv）单独的媒介物。评价所有动物的：（i）使用静脉内辣根过氧化物酶（HRP）注射和内皮屏障抗原（EBA）免疫染色的血脑屏障（BBB）破坏;（ii）使用H&E染色、银染色和胶质细胞酸性蛋白（GFAP）免疫染色的神经元细胞死亡;和（iii）乙酰胆碱酯酶（AChE）活性和m2-毒蕈碱乙酰胆碱受体（m2-AChR）。受到压力和化学品的动物表现出破坏的血脑屏障和神经元细胞死亡的扣带皮层，齿状回，丘脑和下丘脑。大脑的其他区域，虽然它们表现出一些神经元细胞死亡，但没有表现出BBB的破坏。上述四个脑区的神经病理改变均高度显著，并以大量HRP阳性神经元显示（占总神经元的21-40%），EBA免疫染色减少（减少42- 51%），存活神经元数量减少（减少27-40%）、存在垂死神经元（总神经元的4-10%）和增加的GFAP免疫染色（增加45- 51%）。这些变化还与前脑AChE活性和m2-AchR降低（降低19-25%）有关。相比之下，在暴露于应激和溶剂或单独化学品的动物中，上述指数大多与暴露于单独溶剂的动物相当。因此，联合暴露于压力和低剂量的PB，避蚊胺，和氯菊酯导致显着的脑损伤。海湾战争退伍军人报告的各种神经系统症状可能与战争期间发生的这种脑损伤有关。(C)2002 Elsevier Science（美国）
We investigated the effects of a combined exposure to restraint stress and low doses of chemicals pyridostigmine bromide (PB), N, N-diethyl-m-toluamide (DEET), and permethrin in adult male rats, a model of Gulf-War syndrome. Animals were exposed daily to one of the following for 28 days: (i) a combination of stress and chemicals (PB, 1.3 mg/kg/day; DEET, 40 mg/kg/day; and permethrin, 0.13 mg/kg/day); (ii) stress and vehicle; (iii) chemicals alone; and (iv) vehicle alone. All animals were evaluated for: (i) the disruption of the blood-brain barrier (BBB) using intravenous horseradish peroxidase (HRP) injections and endothelial barrier antigen (EBA) immunostaining; (ii) neuronal cell death using H&E staining, silver staining, and glial fibrillary acidic protein (GFAP) immunostaining; and (iii) acetylcholinesterase (AChE) activity and m2-muscarinic acetylcholine receptors (m2-AChR). Animals subjected to stress and chemicals exhibited both disruption of the BBB and neuronal cell death in the cingulate cortex, the dentate gyrus, the thalamus, and the hypothalamus. Other regions of the brain, although they demonstrated some neuronal cell death, did not exhibit disruption of the BBB. The neuropathological changes in the above four brain regions were highly conspicuous and revealed by a large number of HRP-positive neurons (21-40% of total neurons), a decreased EBA immunostaining (42-51 % reduction), a decreased number of surviving neurons (27-40% reduction), the presence of dying neurons (4-10% of total neurons), and an increased GFAP immunostaining (45-51 % increase). These changes were also associated with decreased forebrain AChE activity and m2-AchR (19-25% reduction). In contrast, in animals exposed to stress and vehicle or chemicals alone, the above indices were mostly comparable to that of animals exposed to vehicle alone. Thus, a combined exposure to stress and low doses of PB, DEET, and permethrin leads to significant brain injury. The various neurological symptoms reported by Gulf-War veterans could be linked to this kind of brain injury incurred during the war. (C) 2002 Elsevier Science (USA)