BLAST INDUCES OXIDATIVE STRESS, INFLAMMATION, NEURONAL LOSS AND SUBSEQUENT SHORT-TERM MEMORY IMPAIRMENT IN RATS
BLAST INDUCES OXIDATIVE STRESS, INFLAMMATION, NEURONAL LOSS AND SUBSEQUENT SHORT-TERM MEMORY IMPAIRMENT IN RATS
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DOI：
10.1016/j.neuroscience.2013.08.037
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发表时间：
2013-12-03
期刊：
影响因子：
3.3
通讯作者：
Lee, Y. W.
中科院分区：
文献类型：
--
作者：
Cho, H. J.;Sajja, V. S. S. S.;Lee, Y. W.
爆炸超压（BOP）后脑损伤的分子和细胞机制尚不清楚。本研究假设大脑中的促氧化和促炎症途径可能是 BOP 暴露后神经元损失和行为缺陷的原因。将雄性 Sprague-Dawley 大鼠麻醉并暴露于 129.23 +/- 3.01 kPa 的校准 BOP，而对照组仅接受麻醉。原位二氢乙锭荧光染色显示，BOP 显着增加了大脑中活性氧的产生。此外，实时逆转录聚合酶链反应、免疫荧光染色和酶联免疫吸附测定表明，与对照组相比，从 BOP 暴露动物收集的大脑中，促炎介质（例如干扰素-γ 和单核细胞趋化蛋白-1）的 mRNA 和蛋白质表达显着上调。此外，大脑中神经元核的免疫反应性表明，接触 BOP 后神经元数量减少。此外，新的物体识别范式显示出 BOP 暴露后两周的短期记忆显着受损。这些结果表明，大脑中的促氧化和促炎症环境可能在 BOP 引起的神经元损失和行为缺陷中发挥潜在作用。它可以为定义爆炸引起的神经创伤（BINT）的病理生理学的分子和细胞基础提供基础。它还将有助于开发选择性针对这些途径的新治疗方法，这些方法在 BINT 的诊断和治疗中具有巨大潜力。 (C) 2013 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Molecular and cellular mechanisms of brain injury after exposure to blast overpressure (BOP) are not clearly known. The present study hypothesizes that pro-oxidative and pro-inflammatory pathways in the brain may be responsible for neuronal loss and behavioral deficits following BOP exposure. Male Sprague-Dawley rats were anesthetized and exposed to calibrated BOP of 129.23 +/- 3.01 kPa while controls received only anesthesia. In situ dihydroethidium fluorescence staining revealed that BOP significantly increased the production of reactive oxygen species in the brain. In addition, real-time reverse transcriptase-polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assay demonstrated a significant up-regulation of mRNA and protein expressions of pro-inflammatory mediators, such as interferon-gamma and monocyte chemoattractant protein-1, in brains collected from BOP-exposed animals compared with the controls. Furthermore, immunoreactivity of neuronal nuclei in brains indicated that fewer neurons were present following BOP exposure. Moreover, novel object recognition paradigm showed a significant impairment in the short-term memory at 2 weeks following BOP exposure. These results suggest that pro-oxidative and pro-inflammatory environments in the brain could play a potential role in BOP-induced neuronal loss and behavioral deficits. It may provide a foundation for defining a molecular and cellular basis of the pathophysiology of blast-induced neurotrauma (BINT). It will also contribute to the development of new therapeutic approaches selectively targeting these pathways, which have great potential in the diagnosis and therapy of BINT. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.