Sepsis-associated neuroinflammation in the spinal cord.

Sepsis-associated neuroinflammation in the spinal cord.
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DOI:
10.1371/journal.pone.0269924
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发表时间:
2022
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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脓毒症患者通常表现为中枢神经系统(CNS)障碍,包括意识受损和谵妄。今天,调节败血症引起的大脑疾病的主要机制被认为是神经炎症。然而,尚不清楚CNS的另一个组成部分脊髓在败血症期间是如何受到影响的。在本研究中,我们通过腹腔注射脂多糖(LPS)来研究脓毒症模型小鼠脊髓的分子和免疫组织化学变化。在脊髓中给药LPS后,促炎细胞因子如白细胞介素(IL)-1β、IL-6和肿瘤坏死因子α mRNA被迅速而剧烈地诱导。LPS注射24小时后,严重的神经元缺血性损伤向灰质扩散,尤其是前角周围,前柱出现全局性水肿改变。免疫染色分析显示脊髓小胶质细胞明显活化和增加,但星形胶质细胞未见明显变化。目前的研究结果表明,脓毒症诱导急性神经炎症,包括脊髓小胶质细胞激活和促炎细胞因子上调,导致脊髓剧烈神经元缺血和白质水肿。
Septic patients commonly present with central nervous system (CNS) disorders including impaired consciousness and delirium. Today, the main mechanism regulating sepsis-induced cerebral disorders is believed to be neuroinflammation. However, it is unknown how another component of the CNS, the spinal cord, is influenced during sepsis. In the present study, we intraperitoneally injected mice with lipopolysaccharide (LPS) to investigate molecular and immunohistochemical changes in the spinal cord of a sepsis model. After LPS administration in the spinal cord, pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha mRNA were rapidly and drastically induced. Twenty-four-hour after the LPS injection, severe neuronal ischemic damage spread into gray matter, especially around the anterior horns, and the anterior column had global edematous changes. Immunostaining analyses showed that spinal microglia were significantly activated and increased, but astrocytes did not show significant change. The current results indicate that sepsis induces acute neuroinflammation, including microglial activation and pro-inflammatory cytokine upregulation in the spinal cord, causing drastic neuronal ischemia and white matter edema in the spinal cord.
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