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Citations to this article

Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice
Elizabeth H. Sinz, … , Donald W. Marion, Timothy R. Billiar
Elizabeth H. Sinz, … , Donald W. Marion, Timothy R. Billiar
Published September 1, 1999
Citation Information: J Clin Invest. 1999;104(5):647-656. https://doi.org/10.1172/JCI6670.
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Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice

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Abstract

Nitric oxide (NO) derived from the inducible isoform of NO synthase (iNOS) is an inflammatory product implicated both in secondary damage and in recovery from brain injury. To address the role of iNOS in experimental traumatic brain injury (TBI), we used 2 paradigms in 2 species. In a model of controlled cortical impact (CCI) with secondary hypoxemia, rats were treated with vehicle or with 1 of 2 iNOS inhibitors (aminoguanidine and L-N-iminoethyl-lysine), administered by Alzet pump for 5 days and 1.5 days after injury, respectively. In a model of CCI, knockout mice lacking the iNOS gene (iNOS–/–) were compared with wild-type (iNOS+/+) mice. Functional outcome (motor and cognitive) during the first 20 days after injury, and histopathology at 21 days, were assessed in both studies. Treatment of rats with either of the iNOS inhibitors after TBI significantly exacerbated deficits in cognitive performance, as assessed by Morris water maze (MWM) and increased neuron loss in vulnerable regions (CA3 and CA1) of hippocampus. Uninjured iNOS+/+ and iNOS–/– mice performed equally well in both motor and cognitive tasks. However, after TBI, iNOS–/– mice showed markedly worse performance in the MWM task than iNOS+/+ mice. A beneficial role for iNOS in TBI is supported.

Authors

Elizabeth H. Sinz, Patrick M. Kochanek, C. Edward Dixon, Robert S.B. Clark, Joseph A. Carcillo, Joanne K. Schiding, Minzhi Chen, Stephen R. Wisniewski, Timothy M. Carlos, Debra Williams, Steven T. DeKosky, Simon C. Watkins, Donald W. Marion, Timothy R. Billiar

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 Total
Citations: 1 1 2 2 3 10 1 7 6 3 7 9 4 7 118 6 10 9 6 13 11 13 14 14 16 10 303
Citation information
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Citations to this article in year 2006 (13)

Title and authors Publication Year
Oxidative Stress in Immature Brain after Traumatic Brain Injury
H Bayır, PM Kochanek, VE Kagan
Developmental Neuroscience 2006
NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease
CA Colton, MP Vitek, DA Wink, Q Xu, V Cantillana, ML Previti, WE van Nostrand, JB Weinberg, B Weinberg, H Dawson
Proceedings of the National Academy of Sciences 2006
Evidence that N-acetylcysteine inhibits TNF-α-induced cerebrovascular endothelin-1 upregulation via inhibition of mitogen- and stress-activated protein kinase
MD Sury, M Frese-Schaper, MK Mühlemann, FT Schulthess, IE Blasig, MG Täuber, SG Shaw, S Christen
Free radical biology & medicine 2006
Alterations of blood IL-8, TGF-beta1 and nitric oxide levels in relation to blood cells in patients with acute brain injury
E Hadidi, M Mojtahedzadeh, MH Paknejad, S Nikfar, MJ Zamani, MA Sahraian, B Eftekhar, MR Khajavi, A Najafi, M Ghaffarzadeh, R Eftekhari, V Soleimani, H Esmaily, MR Rouini, M Abdollahi
Therapy 2006
Alterations of blood IL-8, TGF-β1 and nitric oxide levels in relation to blood cells in patients with acute brain injury
E Hadidi, M Mojtahedzadeh, MH Paknejad, S Nikfar, MJ Zamani, MA Sahraian, B Eftekhar, MR Khajavi, A Najafi, M Ghaffarzadeh, R Eftekhari, V Soleimani, H Esmaily, MR Rouini, M Abdollahi
Therapy 2006
Neuroprotection by Selective Inhibition of Inducible Nitric Oxide Synthase after Experimental Brain Contusion
C Gahm, S Holmin, PN Wiklund, L Brundin, T Mathiesen
Journal of Neurotrauma 2006
Limited Role of Inducible Nitric Oxide Synthase in Blood–Brain Barrier Function after Experimental Subarachnoid Hemorrhage
H Yatsushige, JW Calvert, J Cahill, JH Zhang
Journal of Neurotrauma 2006
Phospholipase A2and spinal cord injury: A novel target for therapeutic intervention
AD Olivas, LJ Noble-Haeusslein
Annals of Neurology 2006
Transgenic mice that overexpress the anti-apoptotic Bcl-2 protein have improved histological outcome but unchanged behavioral outcome after traumatic brain injury
R Tehranian, ME Rose, V Vagni, RP Griffith, S Wu, S Maits, X Zhang, RS Clark, CE Dixon, PM Kochanek, O Bernard, SH Graham
Brain Research 2006
Nitric oxide and its modulators in chronic constriction injury-induced neuropathic pain in rats
AK Naik, SK Tandan, D Kumar, SP Dudhgaonkar
European Journal of Pharmacology 2006
Selective inhibition of inducible nitric oxide synthase reduces neurological deficit but not cerebral edema following traumatic brain injury
G Louin, C Marchand-Verrecchia, B Palmier, M Plotkine, M Jafarian-Tehrani
Neuropharmacology 2006
Polyamine and aminoguanidine treatments to promote structural and functional recovery in the adult mammalian brain after injury: A brief literature review and preliminary data about their combined administration
S Schimchowitsch, JC Cassel
Journal of Physiology-Paris 2006
Stratégies anti-inflammatoires et traumatisme crânien
T Lescot, C Marchand-Verrecchia, L Puybasset
Annales Françaises d’Anesthésie et de Réanimation 2006

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