Hypothermia Attenuates Neuronal Damage via Inhibition of Microglial Activation, Including Suppression of Microglial Cytokine Production and Phagocytosis
Hypothermia Attenuates Neuronal Damage via Inhibition of Microglial Activation, Including Suppression of Microglial Cytokine Production and Phagocytosis
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DOI：
10.1007/s10571-020-00860-z
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发表时间：
2020-05-07
影响因子：
4
通讯作者：
Aoyama, Mineyoshi
中科院分区：
文献类型：
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作者：
Kimura, Tomoka;Toriuchi, Kohki;Aoyama, Mineyoshi
虽然治疗性低温（TH）提供神经保护，TH的神经保护作用的细胞机制尚未完全阐明。在本研究中，我们研究了TH对小胶质细胞活化的影响，以确定低温是否通过小胶质细胞活化减轻神经元损伤。在脂多糖（LPS）刺激后，BV-2小胶质细胞在常温（37 ° C）或低温（33.5 ° C）条件下培养。在低温条件下，促炎细胞因子和诱导型一氧化氮合酶（iNOS）的表达受到抑制。此外，在低温条件下，BV-2细胞对乳胶珠的吞噬作用明显受到抑制。此外，核因子-κ B信号在低温条件下被抑制。最后，在低温条件下与BV-2细胞共培养的神经元中，LPS刺激后神经元损伤减弱。总之，低温通过抑制小胶质细胞活化，包括小胶质细胞iNOS和促炎细胞因子表达和吞噬活性，减轻神经元损伤。研究低温条件下小胶质细胞活化调节的机制有助于开发新的神经保护疗法。
Although therapeutic hypothermia (TH) provides neuroprotection, the cellular mechanism underlying the neuroprotective effect of TH has not yet been fully elucidated. In the present study, we investigated the effect of TH on microglial activation to determine whether hypothermia attenuates neuronal damage via microglial activation. After lipopolysaccharide (LPS) stimulation, BV-2 microglia cells were cultured under normothermic (37 degrees C) or hypothermic (33.5 degrees C) conditions. Under hypothermic conditions, expression of pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) was suppressed. In addition, phagocytosis of latex beads was significantly suppressed in BV-2 cells under hypothermic conditions. Moreover, nuclear factor-kappa B signaling was inhibited under hypothermic conditions. Finally, neuronal damage was attenuated following LPS stimulation in neurons co-cultured with BV-2 cells under hypothermic conditions. In conclusion, hypothermia attenuates neuronal damage via inhibition of microglial activation, including microglial iNOS and pro-inflammatory cytokine expression and phagocytic activity. Investigating the mechanism of microglial activation regulation under hypothermic conditions could contribute to the development of novel neuroprotective therapies.