title: Hydroxyl radical formation is greater in striatal core than in penumbra in a rat model of ischemic stroke.
abstract: Although hydroxyl radical ((*)OH) formation has been implicated in the pathophysiological changes of ischemic stroke, (*)OH production in the core and penumbra regions is not clear. It is extremely important to distinguish penumbra from ischemic core in focal cerebral ischemia studies, because the penumbra contains viable tissue, which can be salvaged by appropriate treatment. This study evaluated (*)OH production in both core and penumbra regions of ischemic striatum during ischemia and reperfusion. Microdialysis probes were placed in striatal tissue of rats subjected to the middle cerebral artery occlusion model of ischemic stroke. The (*)OH-trapping agent 4-hydroxybenzoic acid (4-HBA) was administered by both i.v. and probe infusion. Dialysate levels of the 4-HBA oxidation products, 3,4-dihydroxybenzoic acid (3,4-DHBA), were determined by HPLC-ECD. After microdialysis probe delivery of 4-HBA, (*)OH production was significantly increased in the striatal core during both ischemia and reperfusion. Penumbra (*)OH production increased only during reperfusion. Alterations of 3,4-DHBA concentration in dialysate following i.v. 4-HBA administration were likely related to alterations in tissue blood flow. The findings were confirmed by a greater oxidation of dihydroethidium in the ischemic core than in the penumbra as determined by fluorescent microscopy. The findings of (*)OH production in ischemic striatum are the opposite of those reported for ischemic cortex and suggest critical regional variations in (*)OH production that may have significant clinical implications in the treatment of ischemic stroke.
authors.affiliation: College of Pharmacy, University of New Mexico Health Science Center, Albuquerque, New Mexico.
authors.forename: Shimin
authors.initials: S
authors.lastname: Liu
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.forename: Steven
authors.initials: S
authors.lastname: Peterson
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyake
authors.forename: Val
authors.initials: V
authors.lastname: Vallyathan
authors.forename: Ke Jian
authors.initials: KJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D015314:Dialysis Solutions / Q000737:chemistry*; D004996:Ethidium / Q000031:analogs & derivatives* / Q000378:metabolism; D062385:Hydroxybenzoates / Q000032:analysis; D017665:Hydroxyl Radical / Q000032:analysis* / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D017551:Microdialysis; D023421:Models, Animal; D010226:Parabens / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
chemical_list: D015314:Dialysis Solutions; D062385:Hydroxybenzoates; D010226:Parabens; C067883:dihydroethidium; D017665:Hydroxyl Radical; C009091:protocatechuic acid; D004996:Ethidium; C038193:4-hydroxybenzoic acid