title: Isoflurane protects against injury caused by deprivation of oxygen and glucose in microglia through regulation of the Toll-like receptor 4 pathway.
abstract: Oxygen and glucose deprivation (OGD) are the most important factors related to tissue damage resulting from stroke. Microglial cells have been found to be very vulnerable to ischemia and OGD. It has been reported that isoflurane exposure can protect the mammalian brain from insults such as ischemic stroke; however, the effects of isoflurane on OGD-induced injury in microglia are as yet unknown. In this study, we investigated the effects of isoflurane on OGD-induced injury in microglia. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) revealed that OGD did indeed induce cell death in microglia. However, isoflurane preconditioning attenuated OGD-induced cell death. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated that isoflurane treatment alleviated OGD-induced apoptosis. Toll-like receptor 4 (TLR4) plays a considerable role in the induction of innate immune and inflammatory responses. Our results indicate that isoflurane preconditioning inhibits the upregulation of TLR4 as well as the activation of its downstream molecules, such as c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB), in BV-2 microglia exposed to OGD. Importantly, we also found that isoflurane pretreatment significantly reduces the production of proinflammatory factors such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-β, and nitric oxide (NO). The results indicate that TLR4 and its downstream NF-κB-dependent signaling pathway contribute to the neuroprotection of microglia exposed to OGD/reoxygenation by administration of isoflurane.
authors.affiliation: Department of Anesthesiology, Taizhou Hospital of Zhejiang Province, No. 150 Ximen Street, Linhai, Zhejiang Province, 317000, China.
authors.forename: Hai-Fei
authors.initials: HF
authors.lastname: Xiang
authors.forename: Dong-Hang
authors.initials: DH
authors.lastname: Cao
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Yang
authors.forename: Hui-Qin
authors.initials: HQ
authors.lastname: Wang
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhu
authors.forename: Bin-Hao
authors.initials: BH
authors.lastname: Ruan
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.forename: Ming-Cang
authors.initials: MC
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002460:Cell Line; D005947:Glucose / Q000172:deficiency*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007530:Isoflurane; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose; D010100:Oxygen