title: Lipoxin A4 methyl ester ameliorates cognitive deficits induced by chronic cerebral hypoperfusion through activating ERK/Nrf2 signaling pathway in rats.
abstract: Lipoxin A4 (LXA4) is known for its powerful anti-inflammatory function. Current studies in vitro suggest that LXA4 possesses novel antioxidant effect. The aim of this study is to examine whether Lipoxin A4 methyl ester (LXA4 ME) has neuroprotective effects against chronic cerebral hypoperfusion, and if so, whether the effects of LXA4 ME are associated with its potential antioxidant property. Adult male Sprague-Dawley rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) and randomly assigned into four groups: sham (sham-operated) group, vehicle (BCCAO+normal saline) group, LXA4 ME10 (BCCAO+LXA4 ME 10 ng per day) group and LXA4 ME100 (BCCAO+LXA4 ME 100 ng per day) group. LXA4 ME was administered through intracerebroventricular injection for 2 consecutive weeks. LXA4 ME significantly alleviated spatial learning and memory impairments, as assessed by Morris water maze and inhibited the loss of neurons in the CA1 region of the hippocampus. Biochemically, LXA4 ME phosphorylated extracellular signal regulated kinase (ERK) 1/2 and enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) expression and its nuclear translocation, as well as
  quinone oxidoreductase 1 (NQO1) expression. LXA4 ME reduced lipid peroxidative production in the hippocampus, as measured by immunohistochemical staining for 4-Hydroxynonenal (4-HNE). In addition, LXA4 ME significantly elevated the ratio of Bcl-2/Bax and decreased cleaved caspase-3 expression in the hippocampus. Therefore, these data suggest that LXA4 ME exerts beneficial effects on the cognitive impairment induced by chronic cerebral hypoperfusion through attenuating oxidative injury and reducing neuronal apoptosis in the hippocampus, which is most likely associated with the activation of ERK/Nrf2 signaling pathway.
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang, 050017 Hebei Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang, 050017 Hebei Province, China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei Province, China.
authors.forename: Lining
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang, 050051 Hebei Province, China.
authors.forename: Tianjun
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang, 050051 Hebei Province, China.
authors.forename: Hebo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang, 050051 Hebei Province, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang, 050051 Hebei Province, China.
authors.forename: Hezhen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang, 050017 Hebei Province, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang, 050017 Hebei Province, China; Department of Neurology, Hebei General Hospital, Shijiazhuang, 050051 Hebei Province, China. Electronic address: peiyuanlu@163.com.
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Lv
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D044045:Lipoxins / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D044045:Lipoxins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C573617:lipoxin A4 methyl ester; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Antioxidation; Chronic cerebral hypoperfusion; Extracellular signal regulated kinase; Learning and memory; Lipoxin A(4) methyl ester; Nuclear factor erythroid 2-related factor 2