Enhanced oxidative stress in iNOS-deficient mice after traumatic brain injury: support for a neuroprotective role of iNOS

Bayır, Hülya; Kagan, Valerian E.; Borisenko, Grigory G.; Tyurina, Yulia Y.; Janesko, Keri L.; Vagni, Vincent A.; Billiar, Timothy R.; Williams, Deborah L.; Kochanek, Patrick M.

doi:10.1038/sj.jcbfm.9600068

Cited by 138Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchNitric Oxide and Endothelin Effects

Enhanced oxidative stress in iNOS-deficient mice after traumatic brain injury: support for a neuroprotective role of iNOS

Open access

Bayır, Hülya, Kagan, Valerian E., Borisenko, Grigory G., Tyurina, Yulia Y., Janesko, Keri L., Vagni, Vincent A., Billiar, Timothy R., Williams, Deborah L. +1 more·2005·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1038/sj.jcbfm.9600068

Open this paper in CoChat — free account Open PDF

Abstract

Studies in experimental traumatic brain injury (TBI) suggest both deleterious and protective effects of inducible nitric oxide synthase (iNOS). Early after injury, iNOS may be detrimental via formation of peroxynitrite and iNOS inhibitors are protective. In contrast, we reported impaired long-term functional outcome after TBI in iNOS knockout (ko) versus wild-type (wt) mice. To elucidate potential neuroprotective and neurotoxic mechanisms for iNOS, we studied nitric oxide formation by electron paramagnetic resonance (EPR) spectroscopy using diethyldithiocarbamate—iron (DETC—Fe) as a spin trap and markers of nitrosative ( S-nitrosothiol (RSNO, Fluorescent assay); nitrotyrosine (3NT, ELISA)) and oxidative stress (ascorbate, HPLC) at 72 h after controlled cortical impact (CCI) in iNOS ko and wt and in uninjured iNOS ko and wt mice. 3NT immunostaining with macrophage and myeloperoxidase (MPO) dual labeling was also assessed in brain sections. Brain DETC—Fe—NO low-temperature EPR signal intensity was ∼2-fold greater in wt versus iNOS ko at 72 h after CCI. Ascorbate levels decreased in injured hemisphere in wt and iNOS ko versus uninjured —this decrease was more pronounced in iNOS ko. In wt mice, RSNO and 3NT levels were increased after CCI versus uninjured (50% and 400%, respectively, P<0.05). RSNO levels were not increased in iNOS ko after CCI. Nitrotyrosine levels increased after CCI in wt and ko versus respective uninjured —this increase was more pronounced in wt (2.34±0.95 versus 1.27±0.49 pmol/mg protein, P<0.05). Increased 3NT immunoreactivity was detected in wt versus iNOS ko at 72 h after CCI, and colocalized with macrophage marker and MPO. Our data support a role for iNOS-derived NO as an endogenous antioxidant after CCI. iNOS also contributes protein nitrosylation and nitration. Colocalization of 3NT with macrophages and MPO suggests generation of nitrating agents by macrophages and/or phagocytosis of nitrated proteins.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/sj.jcbfm.9600068

Cites

72 of 72 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Oxidative stress occurring after TBI contributes both to microvascular damage and to neuronal damage.
“The oxidative stress occurring after TBI contributes both to microvascular damage and to neuronal damage (97, 124, 125).”
From Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach (2015) · cites this paper as [124]
The Introduction (page unavailable) says oxidative stress is detrimental after TBI, supporting the general claim of damage. The paper does not say that this stress contributes to microvascular damage, and its Assessment of Neuropathology (page unavailable) does not establish a direct link to neuronal damage. (LLM, conf=0.83)
Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide
Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., & Freeman, B. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.4.1620 · Cited by 7,029 · see citing works
A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds
Lipton, S. A., Choi, Y.-B., Pan, Z.-H., Lei, S. Z., Chen, H.-S. V., Sucher, N. J., Loscalzo, J., Singel, D. J., & Stamler, J. S. (1993) · Nature · doi:10.1038/364626a0 · Cited by 2,433 · see citing works
Ascorbate is an outstanding antioxidant in human blood plasma
Frei, B., England, L., & Ames, B. N. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.16.6377 · Cited by 1,870 · see citing works
Effects of Cerebral Ischemia in Mice Deficient in Neuronal Nitric Oxide Synthase
Huang, Z., Huang, P. L., Panahian, N., Dalkara, T., Fishman, M. C., & Moskowitz, M. A. (1994) · Science · doi:10.1126/science.7522345 · Cited by 1,562 · see citing works
S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds.
Stamler, J. S., Simon, D. I., Osborne, J. A., Mullins, M. E., Jaraki, O., Michel, T. M., Singel, D. J., & Loscalzo, J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.1.444 · Cited by 1,471 · see citing works
Fas-Induced Caspase Denitrosylation
Mannick, J. B., Hausladen, A., Liu, L., Hess, D. T., Zeng, M., Miao, Q., Kane, L. S., Gow, A. J., & Stamler, J. S. (1999) · Science · doi:10.1126/science.284.5414.651 · Cited by 743 · see citing works
Enlarged Infarcts in Endothelial Nitric Oxide Synthase Knockout Mice are Attenuated by Nitro-L-Arginine
Huang, Z., Huang, P. L., Ma, J., Meng, W., Ayata, C., Fishman, M. C., & Moskowitz, M. A. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199609000-00023 · Cited by 718 · see citing works
Myeloperoxidase, a Leukocyte-Derived Vascular NO Oxidase
Eiserich, J. P., Baldus, S. E., Brennan, M., Ma, W., Zhang, C., Tousson, A., Castro, L., Lusis, A. J., Nauseef, W. M., White, C. R., et al. (2002) · Science · doi:10.1126/science.1106830 · Cited by 685 · see citing works
Delayed Reduction of Ischemic Brain Injury and Neurological Deficits in Mice Lacking the Inducible Nitric Oxide Synthase Gene
Iadecola, C., Zhang, F., Casey, R., Nagayama, M., & Ross, M. E. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-23-09157.1997 · Cited by 661 · see citing works
Noradrenergic mechanisms in stress and anxiety: I. preclinical studies
Bremner, J., Krystal, J., Southwick, S., & Charney, D. (1996) · Synapse · doi:10.1002/(sici)1098-2396(199605)23:1 · Cited by 571 · see citing works
Proteomic identification of nitrated proteins in Alzheimer's disease brain
Castegna, A., Thongboonkerd, V., Klein, J. B., Lynn, B. C., Markesbery, W. R., & Butterfield, D. A. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01786.x · Cited by 535 · see citing works
Tyrosine nitration: Localisation, quantification, consequences for protein function and signal transduction
Greenacre, S., & Ischiropoulos, H. (2001) · Free Radical Research · doi:10.1080/10715760100300471 · Cited by 500 · see citing works
Inducible Nitric Oxide Synthase Gene Expression in Brain following Cerebral Ischemia
Iadecola, C., Zhang, F., Xu, S., Casey, R., & Ross, M. E. (1995) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1995.47 · Cited by 469 · see citing works
NO-dependent protein nitration: a cell signaling event or an oxidative inflammatory response?
Schopfer, F. J. (2003) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.10.006 · Cited by 369 · see citing works
S-Nitrosylation of mitochondrial caspases
Mannick, J. B., Schonhoff, C. M., Papeta, N., Ghafourifar, P., Szibor, M., Fang, K., & Gaston, B. M. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200104008 · Cited by 363 · see citing works
Neutrophil Accumulation After Traumatic Brain Injury in Rats: Comparison of Weight Drop and Controlled Cortical Impact Models
Clark, R. S. B., Schiding, J. K., Kaczorowski, S. L., Marion, D. W., & Kochanek, P. M. (1994) · Journal of Neurotrauma · doi:10.1089/neu.1994.11.499 · Cited by 291 · see citing works
Self-citation
The NOS inhibitor, 7-nitroindazole, decreases focal infarct volume but not the response to topical acetylcholine in pial vessels
Yoshida, T., Limmroth, V., Irikura, K., & Moskowitz, M. A. (1994) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1994.123 · Cited by 286 · see citing works
Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo
Schulz, J. B., Matthews, R., Jenkins, B. G., Ferrante, R. J., Siwek, D. F., Henshaw, D. R., Cipolloni, P. B., Mecocci, P., Kowall, N. W., & Rosen, B. R. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-12-08419.1995 · Cited by 281 · see citing works
Generation of EPR-detectable nitrosyl-iron complexes in tumor target cells cocultured with activated macrophages
Drapier, J., Pellat‐Deceunynck, C., & Henry, Y. A. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99204-5 · Cited by 279 · see citing works
Protective effects of liposome‐entrapped superoxide dismutase on posttraumatic brain edema
Chan, P. H., Longar, S., & Fishman, R. A. (1987) · Annals of Neurology · doi:10.1002/ana.410210604 · Cited by 279 · see citing works
Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children
Bayır, H., Kagan, V. E., Tyurina, Y. Y., Tyurin, V. A., Ruppel, R. A., Adelson, P. D., Graham, S. H., Janesko, K. L., Clark, R. S. B., & Kochanek, P. M. (2002) · Pediatric Research · doi:10.1203/00006450-200205000-00005 · Cited by 258 · see citing works
Self-citation
Effects of intravenous methylprednisolone on spinal cord lipid peroxidation and (Na+ + K+)-ATPase activity
Hall, E. D., & Braughler, J. M. (1982) · Journal of neurosurgery · doi:10.3171/jns.1982.57.2.0247 · Cited by 256 · see citing works
Nitric Oxide Inhibition of Lipid Peroxidation: Kinetics of Reaction with Lipid Peroxyl Radicals and Comparison with α-Tocopherol
O’Donnell, V. B., Chumley, P. H., Hogg, N., Bloodsworth, A., Darley-Usmar, V. M., & Freeman, B. Α. (1997) · Biochemistry · doi:10.1021/bi971891z · Cited by 253 · see citing works
Oxidative Stress Following Traumatic Brain Injury in Rats
Tyurin, V. A., Tyurina, Y. Y., Borisenko, G. G., Соколова, Т. В., Ritov, V. B., Quinn, P. J., Rose, M. E., Kochanek, P. M., Graham, S. H., & Kagan, V. E. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0752178.x · Cited by 249 · see citing works
Self-citation
Apoptosis-Suppressor Genebcl-2Expression after Traumatic Brain Injury in Rats
Clark, R. S. B., Chen, J., Watkins, S. C., Kochanek, P. M., Chen, M., Stetler, R. A., Loeffert, J. E., & Graham, S. H. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-23-09172.1997 · Cited by 246 · see citing works
Self-citation
Biochemical, cellular, and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: Lessons learned from the bedside
Kochanek, P. M., Clark, R. S. B., Ruppel, R. A., Adelson, P. D., Bell, M. J., Whalen, M. J., Robertson, C., Satchell, M. A., Seidberg, N. A., Marion, D. W., et al. (2000) · Pediatric Critical Care Medicine · doi:10.1097/00130478-200007000-00003 · Cited by 245 · see citing works
Self-citation
Peroxynitrite-Mediated Protein Nitration and Lipid Peroxidation in a Mouse Model of Traumatic Brain Injury
Hall, E. D., Detloff, M. R., Johnson, K., & Kupina, N. C. (2004) · Journal of Neurotrauma · doi:10.1089/089771504772695904 · Cited by 242 · see citing works
Characterization and quantification of the peroxidase in human monocytes
Bos, A., Wever, R., & Roos, D. (1978) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(78)90197-3 · Cited by 238 · see citing works
Nitric oxide prevents tumor necrosis factor α-induced rat hepatocyte apoptosis by the interruption of mitochondrial apoptotic signaling through S-nitrosylation of caspase-8
Kim, Y. M., Kim, T., Chung, H., Talanian, R. V., Yin, X., & Billiar, T. R. (2000) · Hepatology · doi:10.1053/jhep.2000.18291 · Cited by 233 · see citing works
Self-citation
Experimental Autoimmune Encephalomyelitis Is Exacerbated in Mice Lacking the NOS2 Gene
Fenyk-Melody, J. E., Garrison, A. E., Brunnert, S. R., Weidner, J. R., Shen, F. H., Shelton, B. A., & Mudgett, J. S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.6.2940 · Cited by 224 · see citing works
Nitric Oxide Novel Biology with Clinical Relevance
Billiar, T. R. (1995) · Annals of Surgery · doi:10.1097/00000658-199504000-00003 · Cited by 218 · see citing works
Self-citation
Expression of Inducible Nitric Oxide Synthase after Focal Cerebral Ischemia Stimulates Neurogenesis in the Adult Rodent Dentate Gyrus
Zhu, D. Y., Liu, S. H., Sun, H., & Lu, Y. M. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00223.2003 · Cited by 216 · see citing works
Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice
Sinz, E. H., Kochanek, P. M., Dixon, C. E., Clark, R. S. B., Carcillo, J. A., Schiding, J. K., Chen, M., Wisniewski, S. R., Carlos, T. M., Williams, D., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6670 · Cited by 211 · see citing works
Self-citation
Direct evidence of NO production in rat hippocampus and cortex using a new fluorescent indicator
Kojima, H., Nakatsubo, N., Kikuchi, K., Urano, Y., Higuchi, T., Tanaka, J., Kudo, Y., & Nagano, T. (1998) · Neuroreport · doi:10.1097/00001756-199810260-00001 · Cited by 201 · see citing works
Oxidative post‐translational modifications of α‐synuclein in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of Parkinson's disease
Przedborski, S., Chen, Q., Vila, M., Giasson, B. I., Djaldatti, R., Vukosavić, S., Souza, J. M., Jackson-Lewis, V. R., Lee, V. M. ‐., & Ischiropoulos, H. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00174.x · Cited by 190 · see citing works
Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats
Wada, K., Chatzipanteli, K., Kraydieh, S., Busto, R., & Dietrich, W. D. (1998) · Neurosurgery · doi:10.1097/00006123-199812000-00096 · Cited by 186 · see citing works
Nitric oxide prevents IL-1beta and IFN-gamma-inducing factor (IL-18) release from macrophages by inhibiting caspase-1 (IL-1beta-converting enzyme).
Kim, Y., Talanian, R. V., Li, J., & Billiar, T. R. (1998) · PubMed · Cited by 181 · see citing works
Self-citation
Nitric Oxide Prevents IL-1β and IFN-γ-Inducing Factor (IL-18) Release from Macrophages by Inhibiting Caspase-1 (IL-1β-Converting Enzyme)
Kim, Y., Talanian, R. V., Li, J., & Billiar, T. R. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.8.4122 · Cited by 168 · see citing works
Self-citation
Inducible Nitric Oxide Synthase Expression in Cerebrovascular Smooth Muscle and Neutrophils after Traumatic Brain Injury in Immature Rats1
Clark, R. S. B., Kochanek, P. M., Schwarz, M. A., Schiding, J. K., Turner, D. S., Chen, M., Carlos, T. M., & Watkins, S. C. (1996) · Pediatric Research · doi:10.1203/00006450-199605000-00007 · Cited by 164 · see citing works
Self-citation
Reduction of Cognitive and Motor Deficits after Traumatic Brain Injury in Mice Deficient in Poly(ADP-Ribose) Polymerase
Whalen, M. J., Clark, R. S. B., Dixon, C. E., Robichaud, P., Marion, D. W., Vagni, V., Graham, S. H., Virág, L., Haskó, G., Stachlewitz, R. F., et al. (1999) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199908000-00002 · Cited by 156 · see citing works
Self-citation
Selective inhibition of inducible nitric oxide synthase prevents ischaemic brain injury
Parmentier, S., Böhme, G. A., Lerouet, D., Damour, D., Stutzmann, J. M., Margaill, I., & Plotkine, M. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702549 · Cited by 155 · see citing works
Differential IgE recognition of recombinant Aspergillus fumigatus allergens by cystic fibrosis patients with allergic bronchopulmonary aspergillosis or Aspergillus allergy
Hemmann, S., Nikolaizik, W. H., Schöni, M. H., Blaser, K., & Crameri, R. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199804)28:04 · Cited by 130 · see citing works
Excitatory amino acid concentrations in ventricular cerebrospinal fluid after severe traumatic brain injury in infants and children: The role of child abuse
Ruppel, R. A., Kochanek, P. M., Adelson, P. D., Rose, M. E., Wisniewski, S. R., Bell, M. J., Clark, R. S. B., Marion, D. W., & Graham, S. H. (2001) · The Journal of Pediatrics · doi:10.1067/mpd.2001.110979 · Cited by 128 · see citing works
Self-citation
Elevated Levels of <i>S</i> -Nitrosoalbumin in Preeclampsia Plasma
Tyurin, V. A., Liu, S.-X., Tyurina, Y. Y., Sussman, N. B., Hubel, C. A., Roberts, J. M., Taylor, R. N., & Kagan, V. E. (2001) · Circulation Research · doi:10.1161/hh1101.092179 · Cited by 120 · see citing works
Self-citation
L-Arginine and Superoxide Dismutase Prevent or Reverse Cerebral Hypoperfusion after Fluid-Percussion Traumatic Brain Injury
DeWitt, D. S., Smith, T. G., Deyo, D. J., MILLER, K. R., Uchida, T., & Prough, D. S. (1997) · Journal of Neurotrauma · doi:10.1089/neu.1997.14.223 · Cited by 114 · see citing works
Brain Nitric Oxide Changes After Controlled Cortical Impact Injury in Rats
Cherian, L., Goodman, J. C., & Robertson, C. S. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.83.4.2171 · Cited by 112 · see citing works
Cerebrospinal fluid and plasma nitrite and nitrate concentrations after head injury in humans
Clark, R. S. B., Kochanek, P. M., Obrist, W. D., Wong, H. R., Billiar, T. R., Wisniewski, S. R., & Marion, D. W. (1996) · Critical Care Medicine · doi:10.1097/00003246-199607000-00030 · Cited by 110 · see citing works
Self-citation
EPR evidence for nitric oxide production from guanidino nitrogens of l-arginine in animal tissues in vivo
Kubrina, L. N., Caldwell, W. S., Mordvintcev, P. I., Malenkova, I. V., & Vanin, A. F. (1992) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(92)90032-w · Cited by 107 · see citing works
Delayed peripheral Nerve Degeneration, Regeneration, and pain in Mice Lacking Inducible Nitric Oxide Synthase
Levy, D., Kubes, P., & Zochodne, D. W. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.5.411 · Cited by 104 · see citing works
Gene-dosing effect and persistence of reduction in ischemic brain injury in mice lacking inducible nitric oxide synthase
Zhao, X., Haensel, C., Araki, E., et al. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02459-8 · Cited by 98 · see citing works
Delayed Treatment with Aminoguanidine Decreases Focal Cerebral Ischemic Damage and Enhances Neurologic Recovery in Rats
Nagayama, M., Zhang, F., & Iadecola, C. (1998) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199810000-00007 · Cited by 98 · see citing works
Nitric Oxide
Mohanakumar, K. P., Thomas, B., Sharma, S. M., Muralikrishnan, D., Chowdhury, R., & Chiueh, C. C. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04083.x · Cited by 94 · see citing works
Peroxynitrite Reaction with Heme Proteins
Mehl, M., Daiber, A., Herold, S., Shoun, H., & Ullrich, V. (1999) · Nitric Oxide · doi:10.1006/niox.1999.0217 · Cited by 87 · see citing works
Electron Paramagnetic Resonance (EPR) Detection of Nitric Oxide Produced during Forebrain Ischemia of the Rat
Tominaga, T., Sato, S., Ohnishi, T., et al. (1994) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1994.92 · Cited by 87 · see citing works
Role of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Endotoxin-Induced Cerebral Hyperemia
Okamoto, H., Ito, O., Roman, R. J., et al. (1998) · Stroke · doi:10.1161/01.str.29.6.1209 · Cited by 77 · see citing works
Induction of nitric oxide synthase by traumatic brain injury
Orihara, Y., Ikematsu, K., Tsuda, R., et al. (2001) · Forensic Science International · doi:10.1016/s0379-0738(01)00537-0 · Cited by 76 · see citing works
Induction of nitric oxide synthase activity in rodent brain following middle cerebral artery occlusion
Yoshida, T., Waeber, C., Huang, Z., et al. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11752-i · Cited by 76 · see citing works
Nitration of the Low Molecular Weight Neurofilament Is Equivalent in Sporadic Amyotrophic Lateral Sclerosis and Control Cervical Spinal Cord
Strong, M. J., Sopper, M. M., Crow, J. P., Strong, W., & Beckman, J. S. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8930 · Cited by 73 · see citing works
Deoxynucleoside and vitamin transport into the central nervous system.
Spector, R., & Eells, J. T. (1984) · PubMed · Cited by 58 · see citing works
Accelerated S-Nitrosothiol Breakdown by Amyotrophic Lateral Sclerosis Mutant Copper,Zinc-Superoxide Dismutase
Johnson, M. A., Macdonald, T. L., Mannick, J. B., Conaway, M. R., & Gaston, B. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102781200 · Cited by 56 · see citing works
Nitric Oxide Synthase Expression after Human Brain Contusion
Gahm, C., Holmin, S., & Mathiesen, T. I. (2002) · Neurosurgery · doi:10.1097/00006123-200206000-00024 · Cited by 54 · see citing works
Neuroprotection by aminoguanidine after lateral fluid-percussive brain injury in rats: a combined magnetic resonance imaging, histopathologic and functional study
Lu, J. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(02)00380-5 · Cited by 52 · see citing works
Ascorbic Acid and Glutathione Modulate the Biological Activity of S- Nitrosoglutathione
Xu, A., Vita, J. A., & Keaney, J. F. (2000) · Hypertension · doi:10.1161/01.hyp.36.2.291 · Cited by 47 · see citing works
Ultrastructural Localization of Nitrotyrosine within the Caudate-Putamen Nucleus and the Globus Pallidus of Normal Rat Brain
Bolan, E. A., Gracy, K. N., Chan, J., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-13-04798.2000 · Cited by 39 · see citing works
Drastic increase in nitric oxide content in rat brain under halothane anesthesia revealed by EPR method
Sjakste, N., Baumane, L., Meirena, D., et al. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00281-6 · Cited by 34 · see citing works
Increased S-Nitrosothiols and S-Nitrosoalbumin in Cerebrospinal Fluid After Severe Traumatic Brain Injury in Infants and Children: Indirect Association With Intracranial Pressure
Bayır, H., Kochanek, P. M., Liu, S., Arroyo, A., Osipov, A. N., Jiang, J., Wisniewski, S. R., Adelson, P. D., Graham, S. H., & Kagan, V. E. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000040399.30600.e3 · Cited by 31 · see citing works
Self-citation
Experimental autoimmune encephalomyelitis in mice with a targeted deletion of the inducible nitric oxide synthase gene: increased T-helper 1 response
Kahl, K. G., Schmidt, H. H. H. W., Jung, S., et al. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2003.12.095 · Cited by 30 · see citing works
Role of Nitric Oxide in the Secondary Expansion of a Cortical Brain Lesion from Cold Injury
Stoffel, M. H., Rinecker, M., Plesnila, N., et al. (2001) · Journal of Neurotrauma · doi:10.1089/089771501750171010 · Cited by 29 · see citing works
Aminoguanidine reduces brain lesion volume after cold injury in the rat
Görlach, C., Hortobágyi, T., Benyó, Z., et al. (2000) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s004240000293 · Cited by 18 · see citing works
Cerebrospinal Fluid Ascorbic Acid Levels in Neurological Disorders
Brau, R. H., García-Castiñeiras, S., & Rifkinson, N. (1984) · Neurosurgery · doi:10.1227/00006123-198402000-00004 · Cited by 15 · see citing works
Attenuation of Secondary Lesion Growth in the Brain After Trauma by Selective Inhibition of the Inducible No-Synthase
Stoffel, M. H., Rinecker, M., Plesnila, N., et al. (2000) · Springer eBooks · doi:10.1007/978-3-7091-6346-7_74 · Cited by 15 · see citing works
Direct and Indirect Antioxidant Effects of Nitric Oxide: Radically Unsettled Issues
Kagan, V. E., & Laskin, J. D. (2001) · Antioxidants and Redox Signaling · doi:10.1089/152308601300185142 · Cited by 8 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

Pathophysiology of traumatic brain injury
Werner, C., & Engelhard, K. (2007) · British Journal of Anaesthesia · doi:10.1093/bja/aem131 · Cited by 1,712 · see citing works
The role of the nitric oxide pathway in brain injury and its treatment — From bench to bedside
Garry, P. S., Ezra, M., Rowland, M. J., Westbrook, J., & Pattinson, K. T. S. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2014.10.017 · Cited by 380 · see citing works
Endothelial influences on cerebrovascular tone
Andresen, J., Shafi, N. I., & Bryan, R. M. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00937.2005 · Cited by 235 · see citing works
Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach
Tanriverdi, F., Schneider, H. J., Aimaretti, G., Masel, B. E., Casanueva, F. F., & Kelestimur, F. (2015) · Endocrine Reviews · doi:10.1210/er.2014-1065 · Cited by 218 · see citing works
The Genetic Inactivation of Inducible Nitric Oxide Synthase (iNOS) Intensifies Fibrosis and Oxidative Stress in the Penile Corpora Cavernosa in Type 1 Diabetes
Ferrini, M. G., Rivera, S., Moon, J., Vernet, D., Rajfer, J., & Gonzalez-Cadavid, N. F. (2010) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2010.01884.x · Cited by 60 · see citing works

Nitrotyrosine formation and its role in various pathological conditions
Nakazawa, H. K., Fukuyama, N., Takizawa, S., Tsuji, C., Yoshitake, M., & Ishida, H. (2000) · Free Radical Research · doi:10.1080/10715760000301291 · Cited by 73 · see citing works
Loss of 3-Nitrotyrosine on Exposure to Hypochlorous Acid: Implications for the Use of 3-Nitrotyrosine as a Bio-markerin Vivo
Whiteman, M., & Halliwell, B. B. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0564 · Cited by 37 · see citing works
Anti-Nitrotyrosine Antibodies for Immunohistochemistry
Viera, L., Ye, Y. Z., & Beckman, J. S. (2003) · Humana Press eBooks · doi:10.1385/1-59259-216-3:159 · Cited by 5 · see citing works
Nitrotyrosine in peripheral vascular disease
ROS, R. D., Quagliaro, L., Gasparini, D., et al. (2003) · Journal of Thrombosis and Haemostasis · doi:10.1046/j.1538-7836.2003.00042.x · Cited by 4 · see citing works
Deficiency of Myeloperoxidase Increases Infarct Volume and Nitrotyrosine Formation in Mouse Brain
Takizawa, S., Aratani, Y., Fukuyama, N., Maeda, N., Hirabayashi, H., Koyama, H., Shinohara, Y., & Nakazawa, H. K. (2002) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200201000-00006 · Cited by 53 · see citing works

Authors: Bayır, H., Kagan, V. E., Borisenko, G. G., Tyurina, Y. Y., Janesko, K. L., Vagni, V. A., Billiar, T. R., Williams, D. L., & Kochanek, P. M.
Affiliations: University of Pittsburgh (US)
University of Pittsburgh Medical Center (US)
Corresponding author: Bayır, Hülya
ORCID: Bayır, Hülya
Kagan, Valerian E.
Tyurina, Yulia Y.
Billiar, Timothy R.
Kochanek, Patrick M.
Venue: Journal of Cerebral Blood Flow & Metabolism
Publisher: SAGE Publications
Published: 2005-06
Volume: 25
Issue: 6
Pages: 673-684
ISSN: 0271-678X (ISSN-L)
1559-7016
DOI: 10.1038/sj.jcbfm.9600068
OpenAlex: W2089885268
Cited by: 138
References: 72
Citations by year: 2026: 1 · 2025: 4 · 2024: 4 · 2023: 10 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 12 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 5 · 2012: 8
FWCI: 5.81
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01hl064145-04)
National Heart, Lung, and Blood Institute (HL64145)
National Institute of Neurological Disorders and Stroke (NS-30318)
Topics: Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords: inducible nitric oxide synthase, traumatic brain injury, oxidative stress, nitric oxide, nitrotyrosine, S-nitrosothiols, peroxynitrite, nitrosative stress, protein nitration, protein nitrosylation, macrophages, myeloperoxidase, controlled cortical impact, iNOS knockout mice, neuroprotection
MeSH terms: Animals, Brain, Brain Injuries, Electron Spin Resonance Spectroscopy, Mice, Inbred C57BL, Peroxidase, Nitric Oxide, Tyrosine, Mice, Knockout, Oxidative Stress, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Enhanced oxidative stress in iNOS-deficient mice after traumatic brain injury: support for a neuroprotective role of iNOS

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks