title: Dexmedetomidine confers neuroprotection against transient global cerebral ischemia/reperfusion injury in rats by inhibiting inflammation through inactivation of the TLR-4/NF-κB pathway.
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 (10min); Group D received DXM 30min before ischemia; Group R received resatorvid, a selective TLR-4 antagonist, 30min before ischemia; and Group RD received resatorvid and DXM 30min before ischemia. The numbers of necrotic and apoptotic cells and the levels of TLR-4, NF-κB, and caspase-3 were assessed 1day 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 24h 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 2h after ischemia, whereas IL-6 were higher in Group C 6h after ischemia. IL-1β was higher in Group C than in Group D 6 and 24h 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Daegu Catholic University Medical Center, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea. Electronic address: tomomie@hanmail.net.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Keimyung University Dongsan Hospital, Keimyung University College of Medicine, Daegu, Republic of Korea. Electronic address: onidori1979@gmail.com.
authors.forename: Hyun-Chang
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Daegu Catholic University Medical Center, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea. Electronic address: 11choko11@naver.com.
authors.forename: Seungmi
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: hogeol@gmail.com.
authors.forename: Ho-Geol
authors.initials: HG
authors.lastname: Ryu
authors.affiliation: Department of Anesthesiology and Pain medicine, Chung-Ang University Hospital, Seoul, Republic of Korea. Electronic address: dada822@naver.com.
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Inje University Ilsan Paik Hospital, Gyeonggi, Republic of Korea. Electronic address: ishmael1@naver.com.
authors.forename: Jun Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: limyjin@snu.ac.kr.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Lim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: hppark@snu.ac.kr.
authors.forename: Hee-Pyoung
authors.initials: HP
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004660:Encephalitis / Q000378:metabolism* / Q000517:prevention & control*; D006624:Hippocampus / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; D018696:Neuroprotective Agents; D051197:Toll-Like Receptor 4; D020927:Dexmedetomidine
keywords: Dexmedetomidine; Inflammation; NF-κB; Neuroprotection; TLR-4