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Science 23 September 1994:
Vol. 265. no. 5180, pp. 1883 - 1885
DOI: 10.1126/science.7522345
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Articles

Science, Vol 265, Issue 5180, 1883-1885
Copyright © 1994 by American Association for the Advancement of Science

articles

Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase

Z Huang, PL Huang, N Panahian, T Dalkara, MC Fishman, and MA Moskowitz

Stroke Research Laboratory, Massachusetts General Hospital, Charlestown 02129.

The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased significantly 24 and 72 hours after middle cerebral artery occlusion, and the neurological deficits were less than those in normal mice. This result could not be accounted for by differences in blood flow or vascular anatomy. However, infarct size in the mutant became larger after endothelial NOS inhibition by nitro-L-arginine administration. Hence, neuronal NO production appears to exacerbate acute ischemic injury, whereas vascular NO protects after middle cerebral artery occlusion. The data emphasize the importance of developing selective inhibitors of the neuronal isoform.


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J. Cell Biol. 150, 335-348
   Abstract »    Full Text »    PDF »
Oxygen-Glucose Deprivation Induces Inducible Nitric Oxide Synthase and Nitrotyrosine Expression in Cerebral Endothelial Cells Editorial Comment.
J. Xu, L. He, S. H. Ahmed, S.-W. Chen, M. P. Goldberg, J. S. Beckman, C. Y. Hsu, and C. Iadecola (2000)
Stroke 31, 1744-1751
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Two distinct mechanisms of nitric oxide-mediated neuronal cell death show thiol dependency.
A. J. Gow, Q. Chen, M. Gole, M. Themistocleous, V. M.-Y. Lee, and H. Ischiropoulos (2000)
Am J Physiol Cell Physiol 278, C1099-C1107
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Preferential Inhibition by a Novel Na+/Ca2+ Channel Blocker NS-7 of Severe to Mild Hypoxic Injury in Rat Cerebrocortical Slices: A Possible Involvement of a Highly Voltage-Dependent Blockade of Ca2+ Channel.
M. Oka, Y. Itoh, and Y. Ukai (2000)
J. Pharmacol. Exp. Ther. 293, 522-529
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DNA Methyltransferase Contributes to Delayed Ischemic Brain Injury.
M. Endres, A. Meisel, D. Biniszkiewicz, S. Namura, K. Prass, K. Ruscher, A. Lipski, R. Jaenisch, M. A. Moskowitz, and U. Dirnagl (2000)
J. Neurosci. 20, 3175-3181
   Abstract »    Full Text »    PDF »
Nitric Oxide Deficiency Contributes to Large Cerebral Infarct Size.
G. A. Kidd, L. W. Dobrucki, V. Brovkovych, D. F. Bohr, and T. Malinski (2000)
Hypertension 35, 1111-1118
   Abstract »    Full Text »    PDF »
Blunted respiratory responses to hypoxia in mutant mice deficient in nitric oxide synthase-3.
D. D. Kline, T. Yang, D. R. D. Premkumar, A. J. Thomas, and N. R. Prabhakar (2000)
J Appl Physiol 88, 1496-1508
   Abstract »    Full Text »    PDF »
Nitric Oxide-Related Brain Damage in Acute Ischemic Stroke.
J. Castillo, R. Rama, and A. Davalos (2000)
Stroke 31, 852-857
   Abstract »    Full Text »    PDF »
Modulation of mouse cardiac function in vivo by eNOS and ANP.
R. Gyurko, P. Kuhlencordt, M. C. Fishman, and P. L. Huang (2000)
Am J Physiol Heart Circ Physiol 278, H971-H981
   Abstract »    Full Text »    PDF »
Presenilin-1 Mutation Increases Neuronal Vulnerability to Focal Ischemia In Vivo and to Hypoxia and Glucose Deprivation in Cell Culture: Involvement of Perturbed Calcium Homeostasis.
M. P. Mattson, H. Zhu, J. Yu, and M. S. Kindy (2000)
J. Neurosci. 20, 1358-1364
   Abstract »    Full Text »    PDF »
In situ detection of AP sites and DNA strand breaks bearing 3'-phosphate termini in ischemic mouse brain.
D. HUANG, A. SHENOY, J. CUI, W. HUANG, and P. K. LIU (2000)
FASEB J 14, 407-417
   Abstract »    Full Text »
Spinal Cord Ischemia : Development of a Model in the Mouse Editorial Comment: Development of a Model in the Mouse.
L. Lang-Lazdunski, K. Matsushita, L. Hirt, C. Waeber, J.-P. G. Vonsattel, M. A. Moskowitz, and W. D. Dietrich (2000)
Stroke 31, 208-213
   Abstract »    Full Text »    PDF »
Characterization of Recombinant Human Endothelial Nitric-oxide Synthase Purified from the Yeast Pichia pastoris.
A. Leber, B. Hemmens, B. Klosch, W. Goessler, G. Raber, B. Mayer, and K. Schmidt (1999)
J. Biol. Chem. 274, 37658-37664
   Abstract »    Full Text »    PDF »
Light-Induced Apoptosis in the Neonatal Mouse Retina and Superior Colliculus.
K. Sasaki, H. Ino, T. Chiba, and E. Adachi-Usami (1999)
Invest. Ophthalmol. Vis. Sci. 40, 3079-3083
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Isoforms of Nitric Oxide Synthase in the Optic Nerves of Rat Eyes with Chronic Moderately Elevated Intraocular Pressure.
S. Shareef, A. Sawada, and A. H. Neufeld (1999)
Invest. Ophthalmol. Vis. Sci. 40, 2884-2891
   Abstract »    Full Text »    PDF »
A2A Adenosine Receptor Deficiency Attenuates Brain Injury Induced by Transient Focal Ischemia in Mice.
J.-F. Chen, Z. Huang, J. Ma, J. Zhu, R. Moratalla, D. Standaert, M. A. Moskowitz, J. S. Fink, and M. A. Schwarzschild (1999)
J. Neurosci. 19, 9192-9200
   Abstract »    Full Text »    PDF »
On Ischemic Brain Injury in Genetically Altered Mice.
M. D. Ginsberg (1999)
Arterioscler Thromb Vasc Biol 19, 2581-2583
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MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia.
A. Alessandrini, S. Namura, M. A. Moskowitz, and J. V. Bonventre (1999)
PNAS 96, 12866-12869
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An Inducible Nitric-oxide Synthase (NOS)-associated Protein Inhibits NOS Dimerization and Activity.
E. A. Ratovitski, C. Bao, R. A. Quick, A. McMillan, C. Kozlovsky, and C. J. Lowenstein (1999)
J. Biol. Chem. 274, 30250-30257
   Abstract »    Full Text »    PDF »
Nitric oxide increases persistent sodium current in rat hippocampal neurons.
A K M Hammarstrom and P W Gage (1999)
J. Physiol. 520, 451-461
   Abstract »    Full Text »    PDF »
Ischemic Cell Death in Brain Neurons.
P. Lipton (1999)
Physiol Rev 79, 1431-1568
   Abstract »    Full Text »    PDF »
Hypoxia modulates nitric oxide-induced regulation of NMDA receptor currents and neuronal cell death.
M. Gbadegesin, S. Vicini, S. J. Hewett, D. A. Wink, M. Espey, R. M. Pluta, and C. A. Colton (1999)
Am J Physiol Cell Physiol 277, C673-C683
   Abstract »    Full Text »    PDF »
BN 80933, a dual inhibitor of neuronal nitric oxide synthase and lipid peroxidation: A promising neuroprotective strategy.
P.-E. Chabrier, M. Auguet, B. Spinnewyn, S. Auvin, S. Cornet, C. Demerle-Pallardy, C. Guilmard-Favre, J.-G. Marin, B. Pignol, V. Gillard-Roubert, et al. (1999)
PNAS 96, 10824-10829
   Abstract »    Full Text »    PDF »


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