Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Wada, Koichiro; Chatzipanteli, Katina; Kraydieh, Susan; Busto, Raul; Dietrich, W. Dalton

doi:10.1097/00006123-199812000-00096

Cited by 112 publications

(84 citation statements)

References 62 publications

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“…The role of nitric oxide (NO) in the pathophysiology of cerebral ischemia (Ashwal et al, 1998;Dalkara and Moskowitz, 1994;Iadecola, 1997;Stagliano et al, 1997) and trauma (Wada et al, 1998a;Wada et al, 1998b) has also been documented. In ischemic models, abnormal NO production may be both beneficial and detrimental, depending upon when and where this diffusible neurotransmitter is released (Iadecola, 1997).…”

Section: Biochemical Responsesmentioning

confidence: 99%

“…In contrast, NO produced by endothelial NOS (eNOS) can be of benefit by improving vascular dilation and perfusion (Huang et al, 1996). Generally, NO produced by the inducible form of NOS (iNOS) has been reported in models of cerebral ischemia (del Zoppo et al, 2000) and trauma (Wada et al, 1998b) to have detrimental effects on outcome. Increased iNOS activity generally occurs in a delayed fashion after brain ischemia and trauma and is associated with inflammatory processes.…”

Section: Biochemical Responsesmentioning

confidence: 99%

“…Increased iNOS activity generally occurs in a delayed fashion after brain ischemia and trauma and is associated with inflammatory processes. Pharmacological techniques targeting iNOS activity, such as treatment with aminoguanidine, have been shown to be neuroprotective in both animal models of cerebral ischemia (Iadecola et al, 1995) and trauma (Wada et al, 1998b). However, studies using iNOS knockout mice have implicated iNOS as also being involved with reparative strategies in the more chronic TBI injury setting (Sinz et al, 1999).…”

Section: Biochemical Responsesmentioning

confidence: 99%

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Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

Bramlett

Dietrich

2004

J Cereb Blood Flow Metab

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569

358

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Summary: Current knowledge regarding the pathophysiology of cerebral ischemia and brain trauma indicates that similar mechanisms contribute to loss of cellular integrity and tissue destruction. Mechanisms of cell damage include excitotoxicity, oxidative stress, free radical production, apoptosis and inflammation. Genetic and gender factors have also been shown to be important mediators of pathomechanisms present in both injury settings. However, the fact that these injuries arise from different types of primary insults leads to diverse cellular vulnerability patterns as well as a spectrum of injury processes. Blunt head trauma produces shear forces that result in primary membrane damage to neuronal cell bodies, white matter structures and vascular beds as well as secondary injury mechanisms. Severe cerebral ischemic insults lead to metabolic stress, ionic perturbations, and a complex cascade of biochemical and molecular events ultimately causing neuronal death. Similarities in the pathogenesis of these cerebral injuries may indicate that therapeutic strategies protective following ischemia may also be beneficial after trauma. This review summarizes and contrasts injury mechanisms after ischemia and trauma and discusses neuroprotective strategies that target both types of injuries.

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Section: Biochemical Responsesmentioning

confidence: 99%

Section: Biochemical Responsesmentioning

confidence: 99%

Section: Biochemical Responsesmentioning

confidence: 99%

See 1 more Smart Citation

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

Bramlett

Dietrich

2004

J Cereb Blood Flow Metab

Self Cite

569

358

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“…Peroxynitrite is formed by the chemical reaction of nitric oxide (•NO), produced by nitric oxide synthase (NOS), with superoxide radical (O 2 • −) whenever the two are produced in close proximity (Saran et al, 1990). All three NOS isoforms (eNOS, iNOS, and nNOS), as a key element in production of PN, have been shown to be up-regulated in brain tissue following TBI (Cobbs et al, 1997); (Wada et al, 1998) (Gahm et al, 2000); (Orihara et al, 2001). In addition, a novel isoform of Ca ++ -sensitive NOS (mtNOS), discovered within mitochondria (Bates et al, 1995); (Lopez-Figueroa et al, 2000); (Giulivi, 2003), has been shown to contribute to mitochondrial production of •NO and PN (Radi et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

Deng

Thompson

Gao

et al. 2007

Experimental Neurology

135

171

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We assessed the temporal and spatial characteristics of PN-induced oxidative damage and its relationship to calpain-mediated cytoskeletal degradation and neurodegeneration in a severe unilateral controlled cortical impact (CCI) traumatic brain injury (TBI) model. Quantitative temporal time-course studies were performed to measure two oxidative damage markers: 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE) at 30 min, 1, 3, 6, 12, 24, 48, 72 hrs, 7 days after injury in ipsilateral cortex of young adult male CF-1 mice. Secondly, the time course of Ca ++ -activated, calpain-mediated proteolysis was also analyzed using quantitative western-blot measurement of breakdown products of the cytoskeletal protein α-spectrin. Finally, the time course of neurodegeneration was examined using de Olmos silver staining. Both oxidative damage markers increased in cortical tissue immediately after injury (30 min) and elevated for the first 3-6 hrs before returning to baseline. In the immunostaining study, the PN-selective marker, 3NT, and the lipid peroxidation marker, 4HNE, were intense and overlapping in the injured cortical tissue. α-Spectrin breakdown products, which was used as biomarker for calpain-mediated cytoskeletal degradation, were also increased after injury, but the time course lagged behind the peak of oxidative damage and did not reach its maximum until 24 hrs post-injury. In turn, cytoskeletal degradation preceded the peak of neurodegeneration which occurred at 48 hrs post-injury. These studies have led us to the hypothesis that PN-mediated oxidative damage is an early event that contributes to a compromise of Ca ++ homeostatic mechanisms which causes a massive Ca ++ overload and calpain activation which is a final common pathway that results in post-traumatic neurodegeneration.

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“…4,5 Based on the findings obtained with pharmacological inhibition of NOS or comparisons between NOS-deficient and wildtype mice, both protective 3,6 and harmful [3][4][5] effects of NO in experimental CNS injury have been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Improved functional outcome after spinal cord injury in iNOS-deficient mice

2004

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Study design: Functional outcome was evaluated following experimental compression-type spinal cord injury (SCI) in wild-type mice and knockout mice, lacking the inducible nitric oxide synthase (iNOS) gene. Objectives: To evaluate the role of the nitric oxide generating enzyme iNOS in SCI. Methods: The experimental animals were subjected to an extradural compression of the thoracic spinal cord. Functional outcome was studied during the first 2 weeks post-injury using a scoring system for assessment of hind limb motor function. Results: Injury resulted in initial paraplegia followed by gradual improvement of motor function in most cases. Mice lacking the iNOS gene (iNOSÀ/À) clearly tended to have a better functional outcome than wild-type mice. The difference was significant on day 14 after injury. Conclusion: In accordance with a few earlier experimental studies, showing beneficial effects of pharmacological iNOS inhibition, the present report would indicate a destructive influence of iNOS following spinal cord trauma.

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Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Cited by 112 publications

References 62 publications

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

Improved functional outcome after spinal cord injury in iNOS-deficient mice

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