Protective role of isoflurane pretreatment in rats with focal cerebral ischemia and the underlying molecular mechanism.
Inflammation and immunity are important in the pathogenesis of cerebral ischemia. Toll-like receptor 4 (TLR4) is involved in the inflammatory responses of injured brain tissues. Emerging studies have focused on the effect of isoflurane (ISO) pretreatment on cerebral ischemia, however, the association between ISO pretreatment and TLR4 during cerebral ischemia remains to be elucidated. In the present study, the protective role of ISO pretreatment in rats with focal cerebral ischemia reperfusion was investigated and the molecular mechanism was discussed. Using a middle cerebral artery occlusion (MCAO) model, triphenyltetrazolium chloride staining was utilized to measure the infarct volume and brain edema and immunofluorescence staining was used to detect the MCAO-induced TLR4 expression and localization. Western blot analyses were conducted to quantify the protein expression levels of TLR4, myeloid differentiation primary response 88 (MyD88) and nuclear factor (NF)-κB in ischemic brain tissue at different time points. The results demonstrated that, following ISO pretreatment, the neurological deficits, brain edema and cerebral infarct size caused by ischemia/reperfusion were attenuated. The astrocyte and microglial activation in the brain tissue was decreased. In addition, the expression levels of TLR4, MyD88 and NF-κB were decreased. The present study indicated that ISO pretreatment may protect the brain from ischemic damage by downregulating the expression levels of TLR4, MyD88 and NF-κB.
Department of Anesthesiology, Tangdou Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Zhibin
Z
Xiao
Department of Anesthesiology, Tangdou Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Pengcheng
P
Ren
Department of Stomatology, The 323 Hospital of People's Liberation Army, Xi'an, Shaanxi 710054, P.R. China.
Yang
Y
Chao
Department of Medicine, The 323 Hospital of People's Liberation Army, Xi'an, Shaanxi 710054, P.R. China.
Qianyun
Q
Wang
Department of Anesthesiology, Tangdou Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Jianke
J
Kuai
Department of Anesthesiology, The 323 Hospital of People's Liberation Army, Xi'an, Shaanxi 710054, P.R. China.
Miaomiao
M
Lv
Department of Obstetrics and Gynecology, The Navy General Hospital of People's Liberation Army, Beijing 100059, P.R. China.
Lei
L
Chen
Department of Anesthesiology, Tangdou Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Changjun
C
Gao
Department of Anesthesiology, Tangdou Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Xude
X
Sun
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics
C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D007530:Isoflurane