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Dexmedetomidine confers neuroprotection against transient global cerebral ischemia/reperfusion injury in rats by inhibiting inflammation through inactivation of the TLR-4/NF-?B pathway

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Author(s)
Eugene KimHyun-Chang KimSeungmi LeeHo-Geol RyuYong-Hee ParkJun Hyun KimYoung-Jin LimHee-Pyoung Park
Keimyung Author(s)
Kim, Hyun Chang
Department
Dept. of Anesthesiology & Pain Medicine (마취통증의학)
Journal Title
Neuroscience Letters
Issued Date
2017
Volume
649
Keyword
InflammationDexmedetomidineNeuroprotectionTLR-4NF-κB
Abstract
Dexmedetomidine (DXM) has anti-inflammatory effects, which is considered an important mechanism of DXM-induced neuroprotection from cerebral ischemia/reperfusion injury. We determined whether the anti-inflammatory effects of DXM are associated with inhibition of the toll-like receptor (TLR)-4/nuclear factor kappa B (NF-κB) pathway in a rat model of transient global cerebral ischemia/reperfusion injury. Fifty rats were randomly assigned to one of five groups (10 rats/group): Group S received no treatment; Group C underwent transient global ischemia (10 min); Group D received DXM 30 min before ischemia; Group R received resatorvid, a selective TLR-4 antagonist, 30 min before ischemia; and Group RD received resatorvid and DXM 30 min before ischemia. The numbers of necrotic and apoptotic cells and the levels of TLR-4, NF-κB, and caspase-3 were assessed 1 day after ischemia, and pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) were measured before ischemia and 2, 6, and 24 h thereafter. The necrotic and apoptotic cell counts and levels of TLR-4, NF-κB, and caspase-3 were higher in Group C than in other groups. TNF-α were higher in Group C than in other groups 2 h after ischemia, whereas IL-6 were higher in Group C 6 h after ischemia. IL-1β was higher in Group C than in Group D 6 and 24 h after ischemia. Our findings suggest that the anti-inflammatory action of DXM via inactivation of the TLR-4/NF-κB pathway, in part, may explain DXM-induced neuroprotection after cerebral ischemia.
Keimyung Author(s)(Kor)
김현창
Publisher
School of Medicine
Citation
Eugene Kim et al. (2017). Dexmedetomidine confers neuroprotection against transient global cerebral ischemia/reperfusion injury in rats by inhibiting inflammation through inactivation of the TLR-4/NF-?B pathway. Neuroscience Letters, 649, 20–27. doi: 10.1016/j.neulet.2017.04.011
Type
Article
ISSN
0304-3940
Source
https://www.sciencedirect.com/science/article/pii/S0304394017303026?via%3Dihub
DOI
10.1016/j.neulet.2017.04.011
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/30554
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Anesthesiology & Pain Medicine (마취통증의학)
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