Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

• DOI: 10.1523/jneurosci.1645-07.2007
• Publication Date: 2007-07-04T16:47:53Z
• Authors: Alexander Kunz; Laibaik Park; Takato Abe; Eduardo F. Gallo; Josef Anrather; Ping Zhou; Costantino Iadecola
• Keywords: Nitrotyrosine

Cerebral ischemic preconditioning or tolerance is a powerful neuroprotective phenomenon by which sublethal injurious stimulus renders the brain resistant to subsequent damaging insult. We used lipopolysaccharide (LPS) as in mouse model of middle cerebral artery occlusion (MCAO) examine whether improvements cerebrovascular function contribute protective effect. Administration LPS 24 h before MCAO reduced infarct 68% and improved blood flow (CBF) 114% areas spared from infarction. In addition, prevented dysfunction regulation induced MCAO, demonstrated normalization increase CBF produced neural activity, hypercapnia, endothelium-dependent vasodilator acetylcholine. These beneficial effects were not observed mice lacking inducible nitric oxide synthase (iNOS) nox2 subunit superoxide-producing enzyme NADPH oxidase. increased reactive oxygen species peroxynitrite marker 3-nitrotyrosine wild-type but nulls. The decomposition catalyst 5,10,15, 20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) attenuated LPS-induced nitration counteracted on volume, CBF, vascular reactivity. Thus, preserves neurovascular ameliorates regions territory at risk for This effect mediated formed iNOS-derived NO nox2-derived superoxide. data indicate that preservation an essential component suggest combining neuroprotection vasoprotection may be valuable strategy treating injury.