title: NADPH-oxidase activity is elevated in penumbral and non-ischemic cerebral arteries following stroke.
abstract: Reactive oxygen species play a role in neuronal damage following cerebral ischemia-reperfusion. We tested whether activity of the superoxide-generating enzyme, NADPH-oxidase, is enhanced in cerebral arteries within, adjacent and distant from the ischemic core. The right middle cerebral artery (MCA) of conscious rats was temporarily occluded by perivascular injection of endothelin-1 to induce stroke (ET-1; n=19). Control rats were injected with saline (n=9). At 24 h or 72 h post-administration of ET-1, the MCA and its branches within the ipsilateral penumbra and infarcted core, corresponding arteries in the contralateral hemisphere, and basilar artery were excised. Anatomically similar arteries were excised from saline-injected rats. At 24 h after stroke, NADPH-stimulated superoxide production by arteries from the infarcted core did not differ from levels generated by arteries from control rats, whereas levels were significantly lower 72 h after stroke. However, at both time points after stroke, superoxide production by arteries from the ischemic penumbra was 8-fold greater than levels generated by arteries from control rats. Surprisingly, even in the non-ischemic arteries from the contralateral hemisphere and in the basilar artery, superoxide production was increased approximately 4- to 6-fold at 24 h, but had returned to normal 72 h after stroke. The NADPH-oxidase inhibitor, diphenyleneiodonium, virtually abolished superoxide production by all arteries. Thus, the activity of NADPH-oxidase is enhanced in cerebral arteries from the ischemic penumbra at 24 h and 72 h following cerebral ischemia. Additionally, NADPH-oxidase activity is temporarily enhanced after cerebral ischemia within arteries from non-ischemic parts of the brain.
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia. Allyson.Miller@med.monash.edu.au
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Miller
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.forename: Carli L
authors.initials: CL
authors.lastname: Roulston
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000201:enzymology / Q000503:physiopathology; D002545:Brain Ischemia / Q000201:enzymology* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000201:enzymology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000201:enzymology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007839:Functional Laterality / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D020768:Middle Cerebral Artery / Q000201:enzymology / Q000503:physiopathology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology; D020521:Stroke / Q000201:enzymology* / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D013481:Superoxides; C007517:diphenyleneiodonium; D019255:NADPH Oxidases