Effect of Blast Exposure on the Brain Structure and Cognition in Macaca fascicularis

Effect of Blast Exposure on the Brain Structure and Cognition in Macaca fascicularis
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DOI:
10.1089/neu.2010.1591
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发表时间:
2012-05-01
影响因子:
4.2
通讯作者:
Ling, Eng-Ang
Ling, Eng-Ang
中科院分区:
医学2区
文献类型:
--
作者:
Lu, Jia;Ng, Kian Chye;Ling, Eng-Ang

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脑部爆炸损伤是死亡的主要原因之一,也会严重影响爆炸幸存者的认知以及身体和心理技能。人们对爆炸伤导致认知障碍和其他症状的复杂机制知之甚少。在这项研究中,我们研究了不同程度的初级冲击波超压(BOP;80 和 200 kPa)对病理生理学和磁共振成像(MRI)变化以及神经认知表现的影响,通过猴子剑桥神经心理学测试自动电池(mCANTAB)在非人类灵长类动物(NHP)中进行评估。该研究旨在探讨 NHP 神经行为和组织病理学变化的影响。核磁共振成像和组织病理学揭示了大脑的超微结构变化,特别是小脑的浦肯野神经元和海马的锥体神经元,它们最容易受到爆炸的影响。结果与受影响猴子的行为变化以及运动协调和工作记忆的变化密切相关。此外,白质损伤影响有髓轴突、星形胶质细胞肥大以及星形胶质细胞中水通道蛋白-4 (AQP-4) 表达增加,提示存在脑水肿。爆炸暴露后动物中的星形胶质细胞和少突胶质细胞凋亡似乎增加。小样本量可能导致爆炸后认知表现的不显着结果和有限的定量分析。尽管如此,该研究为建立脑损伤的主要 BOP 阈值提供了初步的描述性变化,为未来旨在估计脑损伤可能性并设定安全暴露限度的研究提供了有用的平台。
Blast injury to the brain is one of the major causes of death and can also significantly affect cognition and physical and psychological skills in survivors of blast. The complex mechanisms via which blast injury causes impairment of cognition and other symptoms are poorly understood. In this study, we investigated the effects of varying degrees of primary blast overpressure (BOP; 80 and 200 kPa) on the pathophysiological and magnetic resonance imaging (MRI) changes and neurocognitive performance as assessed by the monkey Cambridge Neuropsychological Test Automated Battery (mCANTAB) in non-human primates (NHP). The study aimed to examine the effects of neurobehavioral and histopathological changes in NHP. MRI and histopathology revealed ultrastructural changes in the brain, notably in the Purkinje neurons in the cerebellum and pyramidal neurons in the hippocampus, which were most vulnerable to the blast. The results correlated well with the behavioral changes and changes in motor coordination and working memory of the affected monkeys. In addition, there was white matter damage affecting myelinated axons, astrocytic hypertrophy, and increased aquaporin-4 (AQP-4) expression in astrocytes, suggesting cerebral edema. Increased apoptosis appeared to involve astrocytes and oligodendrocytes in the animals following blast exposure. The small sample size could have contributed to the non-significant outcome in cognitive performance post-blast and limited quantitative analyses. Nevertheless, the study has provided initial descriptive changes for establishing a primary BOP threshold for brain injury to serve as a useful platform for future investigations that aim to estimate brain injury potential and set safe limits of exposure.