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Effects of oxygen and glucose deprivation on the expression and distribution of neuronal and inducible nitric oxide synthases and on protein nitration in rat cerebral cortex

Changes in the nitric oxide (NO) system of the rat cerebral cortex were investigated by immunohistochemistry, immunoblotting, NO synthase (NOS) activity assay, and magnetic resonance imaging (MRI) in an experimental model of global cerebral ischemia and reperfusion. Brains were perfused transcardial...

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Published in:Journal of comparative neurology (1911) 2002-02, Vol.443 (2), p.183-200
Main Authors: Alonso, David, Serrano, Julia, Rodríguez, Ignacio, Ruíz-Cabello, Jesús, Fernández, Ana Patricia, Encinas, Juan Manuel, Castro-Blanco, Susana, Bentura, María Luisa, Santacana, María, Richart, Ana, Fernández-Vizarra, Paula, Uttenthal, Lars Otto, Rodrigo, José
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Language:English
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Summary:Changes in the nitric oxide (NO) system of the rat cerebral cortex were investigated by immunohistochemistry, immunoblotting, NO synthase (NOS) activity assay, and magnetic resonance imaging (MRI) in an experimental model of global cerebral ischemia and reperfusion. Brains were perfused transcardially with an oxygenated plasma substitute and subjected to 30 minutes of oxygen and glucose deprivation, followed by reperfusion for up to 12 hours with oxygenated medium containing glucose. A sham group was perfused without oxygen or glucose deprivation, and a further group was treated with the NOS inhibitor Nω‐nitro‐L‐arginine methyl ester (L‐NAME) before and during perfusion. Global ischemia led to cerebrocortical injury as shown by diffusion MRI. This was accompanied by increasing morphologic changes in the large type I interneurons expressing neuronal NOS (nNOS) and the appearance of nNOS immunoreactivity in small type II neurons. The nNOS‐immunoreactive band and calcium‐dependent NOS activity showed an initial increase, followed by a fall after 6 hours of reperfusion. Inducible NOS immunoreactivity appeared in neurons, especially pyramidal cells of layers IV–V, after 4 hours of reperfusion, with corresponding changes on immunoblotting and in calcium‐independent NOS activity. Immunoreactive protein nitrotyrosine, present in the nuclear area of neurons in nonperfused controls and sham‐perfused animals, showed changes in intensity and distribution, appearing in the neuronal processes during the reperfusion period. Prior and concurrent L‐NAME administration blocked the changes on diffusion MRI and attenuated the morphologic changes, suggesting that NO and consequent peroxynitrite formation during ischemia–reperfusion contributes to cerebral injury. J. Comp. Neurol. 443:183–200, 2002. © 2002 Wiley‐Liss, Inc.
ISSN:0021-9967
1096-9861
DOI:10.1002/cne.10111