title: Middle cerebral artery remodeling following transient brain ischemia is linked to early postischemic hyperemia: a target of uric acid treatment.
abstract: Ischemia impairs blood supply to the brain, and reperfusion is important to restore cerebral blood flow (CBF) and rescue neurons from cell death. However, reperfusion can induce CBF values exceeding the basal values before ischemia. This hyperemic effect has been associated with a worse ischemic brain damage, albeit the mechanisms that contribute to infarct expansion are not clear. In this study, we investigated the influence of early postischemic hyperemia on brain damage and middle cerebral artery (MCA) properties and the effect of treatment with the endogenous antioxidant uric acid (UA). The MCA was occluded for 90 min followed by 24 h reperfusion in adult male Sprague-Dawley rats. Cortical CBF increases at reperfusion beyond 20% of basal values were taken as indicative of hyperemia. UA (16 mg/kg) or vehicle (Locke's buffer) was administered intravenously 135 min after MCA occlusion. Hyperemic compared with nonhyperemic rats showed MCA wall thickening (sham: 22.4 ± 0.8 μm; nonhyperemic: 23.1 ± 1.2 μm; hyperemic: 27.8 ± 0.9 at 60 mmHg; P < 0.001, hyperemic vs. sham) involving adventitial cell proliferation, increased oxidative stress, and interleukin-18, and more severe brain damage. Thus MCA remodeling after ischemia-reperfusion takes place under vascular oxidative and inflammatory stress conditions linked to hyperemia. UA administration attenuated MCA wall thickening, induced passive lumen expansion, and reduced brain damage in hyperemic rats, although it did not increase brain UA concentration. We conclude that hyperemia at reperfusion following brain ischemia induces vascular damage that can be attenuated by administration of the endogenous antioxidant UA.
authors: Facultat de Medicina, Departament de Farmacologia, Terapèutica i Toxicologia, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain;
authors: Yara
authors: Y
authors: Onetti
authors: Institut Clínic del Tòrax, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain;
authors: Ana P
authors: AP
authors: Dantas
authors: Facultat de Medicina, Departament de Farmacologia, Terapèutica i Toxicologia, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain;
authors: Belén
authors: B
authors: Pérez
authors: Facultat de Medicina, Departament de Farmacologia, Terapèutica i Toxicologia, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain;
authors: Roger
authors: R
authors: Cugota
authors: Functional Unit of Cerebrovascular Diseases, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; and.
authors: Angel
authors: A
authors: Chamorro
authors: Departament d'Isquèmia Cerebral i Neurodegeneració, Institut de Recerca Biomèdica, Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors: Anna M
authors: AM
authors: Planas
authors: Facultat de Medicina, Departament de Farmacologia, Terapèutica i Toxicologia, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain;
authors: Elisabet
authors: E
authors: Vila
authors: Facultat de Medicina, Departament de Farmacologia, Terapèutica i Toxicologia, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain; francesc.jimenez@uab.cat.
authors: Francesc
authors: F
authors: Jiménez-Altayó
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D006940:Hyperemia / Q000188:drug therapy / Q000503:physiopathology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014527:Uric Acid / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D020382:Interleukin-18; D014527:Uric Acid
keywords: interleukin-18; ischemia-reperfusion; macrophages; oxidative stress; peroxynitrite