title: Peripheral administration of human adrenomedullin and its binding protein attenuates stroke-induced apoptosis and brain injury in rats.
abstract: Stroke is a leading cause of death and the primary medical cause of acquired adult disability worldwide. The progressive brain injury after acute stroke is partly mediated by ischemia-elicited inflammatory responses. The vasoactive hormone adrenomedullin (AM), upregulated under various inflammatory conditions, counterbalances inflammatory responses. However, regulation of AM activity in ischemic stroke remains largely unknown. Recent studies have demonstrated the presence of a specific AM binding protein (that is, AMBP-1) in mammalian blood. AMBP-1 potentiates AM biological activities. Using a rat model of focal cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO), we found that plasma levels of AM increased significantly, whereas plasma levels of AMBP-1 decreased significantly after stroke. When given peripherally early after MCAO, exogenous human AM in combination with human AMBP-1 reduced brain infarct volume 24 and 72 h after MCAO, an effect not observed after the treatment by human AM or human AMBP-1 alone. Furthermore, treatment of human AM/AMBP-1 reduced neuron apoptosis and morphological damage, inhibited neutrophil infiltration in the brain and decreased serum levels of S100B and lactate. Thus, human AM/AMBP-1 has the ability to reduce stroke-induced brain injury in rats. AM/AMBP-1 can be developed as a novel therapeutic agent for patients with ischemic stroke.
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, New York, USA.
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Chaung
authors.forename: Rongqian
authors.initials: R
authors.lastname: Wu
authors.forename: Youxin
authors.initials: Y
authors.lastname: Ji
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
authors.forename: Weifeng
authors.initials: W
authors.lastname: Dong
authors.forename: Cletus
authors.initials: C
authors.lastname: Cheyuo
authors.forename: Lei
authors.initials: L
authors.lastname: Qi
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Qiang
authors.forename: Haichao
authors.initials: H
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D053607:Adrenomedullin / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications; D002316:Cardiotonic Agents / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D007773:Lactates / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D020521:Stroke / Q000150:complications / Q000503:physiopathology
chemical_list: D053607:Adrenomedullin; D002316:Cardiotonic Agents; D017242:Complement Factor H; D007773:Lactates; D009414:Nerve Growth Factors; D009195:Peroxidase; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579158:S100b protein, rat; C493495:CFH protein, human