title: The neuroprotective effects of isoflurane preconditioning in a murine transient global cerebral ischemia-reperfusion model: the role of the Notch signaling pathway.
abstract: Inhalational anesthetic preconditioning can induce neuroprotective effects, and the notch signaling pathway plays an important role in neural progenitor cell differentiation and the inflammatory response after central nervous system injury. This study evaluated whether the neuroprotective effect of isoflurane preconditioning is mediated by the activation of the notch signaling pathway. Mice were divided into two groups consisting of those that did or did not receive preconditioning with isoflurane. The expression levels of notch-1, notch intracellular domain (NICD), and hairy and enhancer of split (HES-1) were measured in mice subjected to transient global cerebral ischemia-reperfusion injury. The notch signaling inhibitor DAPT and conditional notch-RBP-J knockout mice were used to investigate the mechanisms of isoflurane preconditioning-induced neuroprotection. Immunohistochemical staining, real-time polymerase chain reaction assays, and Western blotting were performed. Isoflurane preconditioning induced neuroprotection against global cerebral ischemia. Preconditioning up-regulated the expression of notch-1, HES-1, and NICD after ischemic-reperfusion. However, these molecules were down-regulated at 72 h after ischemic-reperfusion. The inhibition of notch signaling activity by DAPT significantly attenuated the isoflurane preconditioning-induced neuroprotection, and similar results were obtained using notch knockout mice. Our results demonstrate that the neuroprotective effects of isoflurane preconditioning are mediated by the pre-activation of the notch signaling pathway.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Hao-peng
authors.initials: HP
authors.lastname: Zhang
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Sun
authors.forename: Xiao-mei
authors.initials: XM
authors.lastname: Chen
authors.forename: Li-bang
authors.initials: LB
authors.lastname: Yuan
authors.forename: Bin-xiao
authors.initials: BX
authors.lastname: Su
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.forename: Rui-ni
authors.initials: RN
authors.lastname: Zhao
authors.forename: Hai-long
authors.initials: HL
authors.lastname: Dong
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D000818:Animals; D017209:Apoptosis; D001259:Ataxia / Q000209:etiology / Q000517:prevention & control; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000098:blood supply / Q000473:pathology; D017536:Carotid Artery, Common; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000503:physiopathology; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009584:Nitrogen / Q000008:administration & dosage / Q000494:pharmacology; D011292:Premedication; D017434:Protein Structure, Tertiary; D011897:Random Allocation; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D000072056:Transcription Factor HES-1; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004151:Dipeptides; D018398:Homeodomain Proteins; D007530:Isoflurane; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009584:Nitrogen; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C497762:Notch1 protein, mouse