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Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice

Year: 1999
Type: article
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.
DOI: 10.1172/jci6670
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
Language: English
Subfield: Neurology
Field: Medicine
Open Access status: bronze
Funders: American Heart Association, University of Pittsburgh, National Institutes of Health, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medicine, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Awards: G1598042196, Nitric Oxide and Hepatic Function in Sepsis and Trauma, Emerging Therapeutics for TBI - Acute to Chronic Changes, Divergent Pathways of Cell Death after Brain Injury, G6085703389, G6958707378, Emerging Therapeutics for Traumatic Brain Injury (TBI) - Acute to Chronic Changes, Nitric Oxide and Hepatic Function in Sepsis and Trauma
OpenAlex ID: W3158470188
FWCI: 11.27
Cites: 73
Cited by: 211
Related to: 10