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

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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Citations to this article in year 2001 (16)

Title and authors Publication Year
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iNOS and Nitrotyrosine Expression After Spinal Cord Injury
J Xu, GM Kim, S Chen, P Yan, SH Ahmed, G Ku, JS Beckman, XM Xu, CY Hsu 		Journal of Neurotrauma 2001
A Review and Rationale for the Use of Genetically Engineered Animals in the Study of Traumatic Brain Injury
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Detection of Single- and Double-Strand DNA Breaks After Traumatic Brain Injury in Rats: Comparison ofIn SituLabeling Techniques Using DNA Polymerase I, the Klenow Fragment of DNA Polymerase I, and Terminal Deoxynucleotidyl Transferase
RS Clark, M Chen, PM Kochanek, SC Watkins, KL Jin, R Draviam, PD Nathaniel, R Pinto, DW Marion, SH Graham 		Journal of Neurotrauma 2001
Zinc Finger Proteins as Molecular Targets for Nitric Oxide-Mediated Gene Regulation
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Role of Nitric Oxide in the Secondary Expansion of a Cortical Brain Lesion from Cold Injury
M Stoffel, M Rinecker, N Plesnila, J Eriskat, A Baethmann 		Journal of Neurotrauma 2001
Adenovirus-Mediated Transfer and Expression of β-Gal in Injured Hippocampus After Traumatic Brain Injury in Mice
PM Kochanek, KL Janesko, LW Jenkins, HQ Yan, MR Kibbe, P Robichaud, AC Wooditch, RS Clark, CE Dixon, DW Marion, TR Billiar 		Journal of Neurotrauma 2001
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CE Pedraza, MA Baltrons, A Garcı́a 		FEBS Letters 2001
Delayed peripheral Nerve Degeneration, Regeneration, and pain in Mice Lacking Inducible Nitric Oxide Synthase
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Cognitive deficits following blast injury-induced neurotrauma: possible involvement of nitric oxide
IC Jianx 		Brain Injury 2001
Mevastatin, an HMG-CoA Reductase Inhibitor, Reduces Stroke Damage and Upregulates Endothelial Nitric Oxide Synthase in Mice
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