title: Changes in pro-oxidant and antioxidant enzyme levels during cerebral hypoperfusion in rats.
abstract: Chronic cerebral hypoperfusion is a mild ischemic condition associated with a cognitive decline which is prevalent during senescence or Alzheimer's disease. Its experimental animal model compromises permanent occlusion of the common carotid arteries (2VO) in rats, which results in neuronal damage and microglia activation. Various mechanisms, including oxidative stress, have been proposed to be involved in this process. Accordingly, we set out to characterize the changes induced in the expressions of several pro-oxidant and antioxidant enzymes in cerebral hypoperfusion. Male Wistar rats were exposed to 2VO (n=30) or sham operation (n=33), while a third group served as absolute control (naive, n=16). Tissue samples from the hippocampus and frontal cortex were taken 1 and 3 days, 1 and 2 weeks and 3, 6 and 12 months following surgery. Western blot analysis was applied to determine the expressions of cyclooxygenase-2 (COX-2), endothelial, neuronal and inducible nitric oxide synthase (eNOS, nNOS and iNOS, respectively) and manganese superoxide dismutase (MnSOD). During the early phase of hypoperfusion, the COX-2 and eNOS enzyme levels increased in both the hippocampus and the frontal cortex, indicating the presence of excitotoxicity and vascular reactions caused by ischemia, while the expressions of nNOS, iNOS and MnSOD were less affected. There were significant reductions in most of the investigated enzyme levels 2 weeks and 3 months after 2VO induction, which may be a sign of neuronal loss. One year following 2VO onset, the eNOS expression was upregulated, which may strengthen the adaptation of the brain to cerebral ischemia.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Dóm Tér 10, H-6720, Hungary. mracskoeva@gmail.com
authors.forename: Eva
authors.initials: E
authors.lastname: Mracskó
authors.forename: Marietta
authors.initials: M
authors.lastname: Hugyecz
authors.forename: Adám
authors.initials: A
authors.lastname: Institóris
authors.forename: Eszter
authors.initials: E
authors.lastname: Farkas
authors.forename: Ferenc
authors.initials: F
authors.lastname: Bari
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000201:enzymology*; D002545:Brain Ischemia / Q000201:enzymology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015870:Gene Expression; D020869:Gene Expression Profiling; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase