Departments of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
J Inorg Biochem. 2009 Nov;103(11):1555-62. doi: 10.1016/j.jinorgbio.2009.05.019. Epub 2009 Aug 20.
Gulf War Syndrome is a multi-system disorder afflicting many veterans of Western armies in the 1990-1991 Gulf War. A number of those afflicted may show neurological deficits including various cognitive dysfunctions and motor neuron disease, the latter expression virtually indistinguishable from classical amyotrophic lateral sclerosis (ALS) except for the age of onset. This ALS "cluster" represents the second such ALS cluster described in the literature to date. Possible causes of GWS include several of the adjuvants in the anthrax vaccine and others. The most likely culprit appears to be aluminum hydroxide. In an initial series of experiments, we examined the potential toxicity of aluminum hydroxide in male, outbred CD-1 mice injected subcutaneously in two equivalent-to-human doses. After sacrifice, spinal cord and motor cortex samples were examined by immunohistochemistry. Aluminum-treated mice showed significantly increased apoptosis of motor neurons and increases in reactive astrocytes and microglial proliferation within the spinal cord and cortex. Morin stain detected the presence of aluminum in the cytoplasm of motor neurons with some neurons also testing positive for the presence of hyper-phosphorylated tau protein, a pathological hallmark of various neurological diseases, including Alzheimer's disease and frontotemporal dementia. A second series of experiments was conducted on mice injected with six doses of aluminum hydroxide. Behavioural analyses in these mice revealed significant impairments in a number of motor functions as well as diminished spatial memory capacity. The demonstrated neurotoxicity of aluminum hydroxide and its relative ubiquity as an adjuvant suggest that greater scrutiny by the scientific community is warranted.
海湾战争综合征是一种多系统疾病，影响了 20 世纪 90 年代至 1991 年海湾战争中西方军队的许多退伍军人。许多受影响的人可能表现出神经缺陷，包括各种认知功能障碍和运动神经元疾病，后者的表现除了发病年龄外与经典的肌萎缩侧索硬化症（ALS）几乎无法区分。这种 ALS“集群”是迄今为止文献中描述的第二个 ALS 集群。GWS 的可能原因包括炭疽疫苗中的几种佐剂和其他一些原因。最有可能的罪魁祸首似乎是氢氧化铝。在一系列初步实验中，我们检查了皮下注射相当于人类两次剂量的氢氧化铝对雄性、近交 CD-1 小鼠的潜在毒性。处死动物后，通过免疫组织化学检查脊髓和运动皮层样本。用铝处理的小鼠显示运动神经元凋亡明显增加，脊髓和皮层内反应性星形胶质细胞和小胶质细胞增殖增加。Morin 染色检测到运动神经元细胞质中存在铝，一些神经元也检测到存在过度磷酸化的 tau 蛋白，这是包括阿尔茨海默病和额颞叶痴呆在内的多种神经退行性疾病的病理标志。进行了第二组在注射六剂氢氧化铝的小鼠上进行的实验。这些小鼠的行为分析显示，多项运动功能显著受损，空间记忆能力下降。氢氧化铝的神经毒性及其作为佐剂的相对普遍性表明，科学界需要进行更严格的审查。
