| Project/Area Number |
22791435
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Yamaguchi University |
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Principal Investigator |
MATSUI Tomohiro 山口大学, 大学院・医学系研究科, 講師 (50314828)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 脳低温 / マイクログリア / Toll 様受容体 / 低酸素性虚血性脳障害 / 炎症性サイトカイン / 抗炎症性サイトカイン / 一酸化窒素 / ex vivo培養 / 脳低温療法 / TLR3 / IFN-β / NO / ニューロン死 / 低温培養 / TNF-α / IL-10 / TLR / TLR2 / NF-κB / 高温培養 |
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| Research Abstract |
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.
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