title: Post-stroke treatment with miR-181 antagomir reduces injury and improves long-term behavioral recovery in mice after focal cerebral ischemia.
abstract: miR-181 has deleterious effects on stroke outcome, and reducing miR-181a levels prior to middle cerebral artery occlusion (MCAO) was shown previously to be protective. Here we tested the effect of post-ischemic treatment with miR-181a antagomir by intracerebroventricular and intravenous routes of administration on infarct size, neurological outcome, inflammatory response and long term behavioral outcome. Post-treatment with miR-181a antagomir significantly reduced infarction size, improved neurological deficits and reduced NF-κB activation, numbers of infiltrating leukocytes and levels of Iba1. Targets affected by miR-181a antagomir administered after stroke onset include BCL2 and X-linked inhibitor of apoptosis protein (XIAP). Post-treatment with miR-181a antagomir significantly improved behavioral outcome assessed by rotarod at one month. These findings indicate that post-treatment with miR-181a antagomir has neuroprotective effects against ischemic neuronal damage and neurological impairment in mice, and the protection is long lasting including recovery of motor function and coordination over one month. The ability to protect the brain with post-treatment with miR-181a antagomir with long lasting effect makes this a promising therapeutic target and may be an innovative and effective new approach for stroke therapy.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, United States.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Xu
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, United States. Electronic address: ybouyang@stanford.edu.
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Ouyang
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, United States.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, United States.
authors.forename: Creed M
authors.initials: CM
authors.lastname: Stary
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, United States. Electronic address: rona.giffard@stanford.edu.
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D020520:Brain Infarction / Q000188:drug therapy* / Q000209:etiology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D009841:Oligonucleotides / Q000008:administration & dosage*; D009195:Peroxidase / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects*; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D035683:MicroRNAs; D008840:Microfilament Proteins; D009841:Oligonucleotides; C529100:mirn181 microRNA, mouse; D009195:Peroxidase
keywords: BCL2; Focal ischemia; Inflammation; Rotarod; Stroke; XIAP; miR-181a; microRNA