title: Minocycline inhibits 5-lipoxygenase expression and accelerates functional recovery in chronic phase of focal cerebral ischemia in rats.
abstract: OBJECTIVE
  We previously reported that minocycline attenuates acute brain injury and inflammation after focal cerebral ischemia, and this is partly mediated by inhibition of 5-lipoxygenase (5-LOX) expression. Here, we determined the protective effect of minocycline on chronic ischemic brain injury and its relation with the inhibition of 5-LOX expression after focal cerebral ischemia.
  
  
  METHODS
  Focal cerebral ischemia was induced by 90 min of middle cerebral artery occlusion followed by reperfusion for 36 days. Minocycline (45 mg/kg) was administered intraperitoneally 2h and 12h after ischemia and then every 12h for 5 days. Sensorimotor function was evaluated 1-28 days after ischemia and cognitive function was determined 30-35 days after ischemia. Thereafter, infarct volume, neuron density, astrogliosis, and 5-LOX expression in the brain were determined.
  
  
  RESULTS
  Minocycline accelerated the recovery of sensorimotor and cognitive functions, attenuated the loss of neuron density, and inhibited astrogliosis in the boundary zone around the ischemic core, but did not affect infarct volume. Minocycline significantly inhibited the increased 5-LOX expression in the proliferated astrocytes in the boundary zone, and in the macrophages/microglia in the ischemic core.
  
  
  CONCLUSIONS
  Minocycline accelerates functional recovery in the chronic phase of focal cerebral ischemia, which may be partly associated with the reduction of 5-LOX expression.
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, 388 Yuhangtang Road, Hangzhou, 310058, Zhejiang, PR China.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Chu
authors.forename: San-Hua
authors.initials: SH
authors.lastname: Fang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yuan-Jun
authors.initials: YJ
authors.lastname: Yin
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Chen
authors.forename: Jian-Hao
authors.initials: JH
authors.lastname: Li
authors.forename: Ji
authors.initials: J
authors.lastname: Sun
authors.forename: Meng-Ling
authors.initials: ML
authors.lastname: Wang
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhang
authors.forename: Er-Qing
authors.initials: EQ
authors.lastname: Wei
mesh_terms: D000377:Agnosia / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function
chemical_list: D016859:Lipoxygenase Inhibitors; D018696:Neuroprotective Agents; D008911:Minocycline