title: Erythromycin pretreatment induces tolerance against focal cerebral ischemia through up-regulation of nNOS but not down-regulation of HIF-1α in rats.
abstract: The purpose of this study was to determine whether the antibiotic erythromycin induces tolerance against focal cerebral ischemia, and the possible underlying mechanism including the involvement of neuronal nitric oxide synthase (nNOS) and hypoxia-inducible factor-1α (HIF-1α). In rat focal cerebral ischemia models, we found that erythromycin preconditioning could significantly decrease the cerebral infarct volume and brain edema. Meanwhile, the neurological deficits from day 4 through 7 after surgery were also remarkably decreased after erythromycin preconditioning. Moreover, erythromycin preconditioning induced significantly increased nNOS levels and decreased HIF-1α levels in both mRNA and protein expression. This study for the first time indicated that erythromycin preconditioning could induce focal brain ischemic tolerance and attenuate brain injury of subsequent transient focal cerebral ischemia. The potential mechanism may be due to up-regulation of nNOS, but the HIF-1α system was not involved.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Lu
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Bo
authors.initials: B
authors.lastname: Qiu
authors.forename: Ri-Miao
authors.initials: RM
authors.lastname: Yang
authors.forename: Zong-Ze
authors.initials: ZZ
authors.lastname: Guo
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002545:Brain Ischemia; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004917:Erythromycin / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D012720:Severity of Illness Index; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D004917:Erythromycin; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat