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Hypothermic and hyperthermic effects on microglial regulation through cross-talk between activation of toll-like receptor and hypoxia-ischemia

通过 Toll 样受体激活和缺氧缺血之间的串扰来调节小胶质细胞的低温和高温效应

基本信息

批准号：
22791435
负责人：
MATSUI Tomohiro
金额：
$ 2.41万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

Activated microglia produce neurotoxic factors, including pro-inflammatory cytokines and nitric oxide (NO), in response to neuronal destruction. Hence, the suppression of the microglial release of these factors may contribute to the neuroprotective effects of therapeutic hypothermia. I examined the effects of hypothermic culture on the production of pro- and anti-inflammatory cytokines and NO in ex vivomicroglia that were derived from mice with hypoxic-ischemic (HI) brain injury, through the stimulation of toll-like receptors (TLRs) that play significant roles in the pathological processes underlying sterile central nervous system injury. Microglia were isolated from HI brain-injured mice and then cultured with TLR2 and TLR4 agonists at 33°C and 37°C. As a result, compared with 37°C, hypothermia (33°C) reduced the production of TNF-α at 6 h and IL-10 and NO at 48 h. In a clinically relevant setting using TLR-activated microglia that were derived from mice with HI brain injury, hypothermia reduced the production of TNF-α, IL-10, and NO in a time-dependent manner, supporting the idea that neuroprotection conferred by therapeutic hypothermia could be related to attenuation of both early-phase TNF-α and late-phase IL-10 and NO released from microglia. In particular, this mechanism may be responsible for HI brain injury.

激活的小胶质细胞会产生神经毒性因子，包括促炎细胞因子和一氧化氮 (NO)，以应对神经元破坏。因此，抑制小胶质细胞释放这些因子可能有助于低温治疗的神经保护作用。我通过刺激在无菌中枢神经系统损伤的病理过程中发挥重要作用的 Toll 样受体 (TLR)，研究了低温培养对来自缺氧缺血 (HI) 脑损伤小鼠的离体小胶质细胞中促炎和抗炎细胞因子以及 NO 产生的影响。从 HI 脑损伤小鼠中分离出小胶质细胞，然后在 33°C 和 37°C 下与 TLR2 和 TLR4 激动剂一起培养。结果，与37°C相比，低温（33°C）减少了6小时时TNF-α的产生以及48小时时IL-10和NO的产生。在使用源自HI脑损伤小鼠的TLR激活小胶质细胞的临床相关环境中，低温以时间依赖性方式减少了TNF-α、IL-10和NO的产生，这支持了这样的观点，即治疗性低温所赋予的神经保护可能与早期阶段TNF-α以及晚期IL-10和NO释放的减弱有关。小胶质细胞。特别是，这种机制可能是 HI 脑损伤的原因。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

DOI：
10.1007/s12028-011-9639-z
发表时间：
2012-10
期刊：
Neurocritical Care
影响因子：
3.5
作者：
T. Matsui;Yukari Motoki;Takafumi Inomoto;Daisuke Miura;Y. Kato;H. Suenaga;K. Hino;J. Nojima
通讯作者：
T. Matsui;Yukari Motoki;Takafumi Inomoto;Daisuke Miura;Y. Kato;H. Suenaga;K. Hino;J. Nojima

Release of Prostaglandin E2 and Nitric Oxide from Spinal Microglia Is Dependent on Activation of p38 Mitogen-Activated Protein Kinase