title: In vivo optical imaging for evaluating the efficacy of edaravone after transient cerebral ischemia in mice.
abstract: Detection and protection of apoptosis, autophagy and neurovascular unit (NVU) are essentially important in understanding and treatment for ischemic stroke patients. In this study, we have conducted an in vivo optical imaging for detecting apoptosis and activation of matrix metalloproteinases (MMPs), then evaluated the protective effect of 2 package types of free radical scavenger edaravone (A and B) on apoptosis, autophagy and NVU in mice after transient middle cerebral artery occlusion (tMCAO). As compared to vehicle treatment, edaravones A and B showed a significant improvement of clinical scores and infarct size at 48 h after 90 min of tMCAO with great reductions of in vivo fluorescent signal for MMPs and early apoptotic annexin V activations. Ex vivo imaging of MMPSense 680 or annexin V-Cy5.5 showed a fluorescent signal, while which was remarkably different between vehicle and edaravone groups, and colocalized with antibody for MMP-9 or annexin V. Edaravone A and B ameliorated the apoptotic neuronal cell death in immunohistochemistry, and activations of MMP-9 and aquaporin 4 with reducing autophagic activations of microtubule-associated protein 1 light chain 3 (LC3) in Western blot. In this study, edaravone in both packages showed a similar strong neuroprotection after cerebral ischemia, which was confirmed with in vivo and ex vivo optical imagings for MMPs and annexin V as well as reducing cerebral infarct, inhibiting apoptotic/autophagic mechanisms, and protecting a part of neurovascular unit.
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Okayama 700-8558, Japan.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shang
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Tian
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishi
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017209:Apoptosis; D001343:Autophagy; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D015153:Blotting, Western; D002544:Cerebral Infarction / Q000473:pathology; D003952:Diagnostic Imaging; D000077553:Edaravone; D005453:Fluorescence; D005455:Fluorescent Antibody Technique; D019084:Fluorescent Antibody Technique, Indirect; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR
chemical_list: D017304:Annexin A5; D016166:Free Radical Scavengers; D020782:Matrix Metalloproteinases; D000077553:Edaravone; D000983:Antipyrine