title: Pranlukast, a cysteinyl leukotriene receptor-1 antagonist, protects against chronic ischemic brain injury and inhibits the glial scar formation in mice.
abstract: We have recently reported the neuroprotective effect of pranlukast (ONO-1078), a cysteinyl leukotriene receptor-1 (CysLT1) antagonist, on cerebral ischemia in rats and mice. In this study, we further determined whether the effect of pranlukast is long lasting and related to the formation of a glial scar in cerebral ischemic mice. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). After ischemia, pranlukast (0.1 mg/kg) was injected intraperitoneally for 5 consecutive days. Neurological deficits and sensorimotor function were determined during 70 days after ischemia. Brain lesion and glial scar formation were detected at the end of the experiment. Pranlukast did not reduce mortality, but significantly improved neurological deficits and promoted sensorimotor recovery during 70 days. At the end of the experiment, pranlukast significantly reduced lesion volume, and increased neuron densities in the cortex and hippocampal CA1 region in the ischemic hemispheres. Importantly, pranlukast also remarkably reduced the thickness of a scar wall in the ischemic hemispheres. These findings indicate that pranlukast has a long-lasting protective effect on focal cerebral ischemia in mice, and inhibit the ischemia-induced glial scar formation, providing further evidence of the therapeutic potential of pranlukast in the treatment of ischemic stroke.
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou Zhejiang 310031, China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Yu
authors.forename: Er-Qing
authors.initials: EQ
authors.lastname: Wei
authors.forename: Meng-Ling
authors.initials: ML
authors.lastname: Wang
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhang
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Zhang
authors.forename: Jie-Qun
authors.initials: JQ
authors.lastname: Weng
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: Zhong
authors.initials: Z
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000150:complications / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D002452:Cell Count / Q000379:methods; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease / Q000188:drug therapy; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D013997:Time Factors; D014048:Tolonium Chloride
chemical_list: D002867:Chromones; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D014048:Tolonium Chloride; C047681:pranlukast