Nitric Oxide (NO) metabolism in the cerebrospinal fluid of patients with severe head injury

Uzan, Mustafa; Tanrıöver, Necmettin; Bozkuş, Hakan; Gümüştaş, Koray; Güzel, Ömer; Kuday, Cengiz

doi:10.1016/s0090-3019(01)00633-4

Cited by 26 publications

(24 citation statements)

References 45 publications

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“…If so, then the accumulation of biomarkers of oxidative stress should be performed to reflect these potentially important differences. Surprisingly, only few studies have been conducted to assess biomarkers of oxidative stress after TBI in children [3,63,64] .…”

Section: Evaluation Of Oxidative Stress In Clinical Tbimentioning

confidence: 99%

Oxidative Stress in Immature Brain after Traumatic Brain Injury

Bayır¹,

Kochanek²,

Kagan³

2006

Dev Neurosci

124

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High oxygen demand along with the abundance of readily oxidizable substrates yielding productive oxidative metabolism are required for the normal function of the brain. This necessitates the existence of the complex and multicomponent antioxidant system in the brain for protection against oxidative damage. However, during development, individual components of the antioxidant system are not equally expressed and not always sufficient to fulfill their tasks in a coordinated way. As a result, the developing brain may be more vulnerable to oxidative insults than the adult brain. Traumatic brain injury is one of the damaging acute impacts that challenge the brain antioxidant reserves by exposing them to a number of decompartmentalized prooxidant molecules. This review focuses on the sources and assessment of oxidative stress and the link between oxidative stress and cell death pathways in the immature brain after experimental and clinical traumatic brain injury.

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Section: Evaluation Of Oxidative Stress In Clinical Tbimentioning

confidence: 99%

Oxidative Stress in Immature Brain after Traumatic Brain Injury

Bayır¹,

Kochanek²,

Kagan³

2006

Dev Neurosci

124

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“…However, systemic cytokine levels can be confounded by extracranial pathology and variable blood–brain barrier leak of centrally derived mediators. Measurement of cerebral levels of cytokines provides a more direct metric of neuroinflammation following TBI, but, to date, the measurement of cerebral microdialysis (CMD) (11–29) and cerebrospinal fluid (CSF) (30–65) cytokines have been limited to small studies.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid and Microdialysis Cytokines in Severe Traumatic Brain Injury: A Scoping Systematic Review

et al. 2017

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ObjectiveTo perform two scoping systematic reviews of the literature on cytokine measurement in: 1. cerebral microdialysis (CMD) and 2. cerebrospinal fluid (CSF) in severe traumatic brain injury (TBI) patients.MethodsTwo separate systematic reviews were conducted: one for CMD cytokines and the second for CSF cytokines. Both were conducted in severe TBI (sTBI) patients only.Data sourcesArticles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to October 2016), reference lists of relevant articles, and gray literature were searched.Study selectionTwo reviewers independently identified all manuscripts utilizing predefined inclusion/exclusion criteria. A two-tier filter of references was conducted.Data extractionPatient demographic and study data were extracted to tables.ResultsThere were 19 studies identified describing the analysis of cytokines via CMD in 267 sTBI patients. Similarly, there were 32 studies identified describing the analysis of CSF cytokines in 1,363 sTBI patients. The two systematic reviews demonstrated: 1. limited literature available on CMD cytokine measurement in sTBI, with some preliminary data supporting feasibility of measurement and associations between cytokines and patient outcome. 2. Various CSF measured cytokines may be associated with patient outcome at 6–12 months, including interleukin (IL)-1b, IL-1ra, IL-6, IL-8, IL-10, and tumor necrosis factor 3. There is little to no literature in support of an association between CSF cytokines and neurophysiologic or tissue outcomes.ConclusionThe evaluation of CMD and CSF cytokines is an emerging area of the literature in sTBI. Further, large prospective multicenter studies on cytokines in CMD and CSF need to be conducted.

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“…After TBI, the activity of endothelial NOS (eNOS) and neuronal NOS (nNOS) peak for anything from a few seconds to a few minutes but activity decreases shortly thereafter to about 50% of baseline, at which level they can remain for up to 7 days (Wada et al, 1998(Wada et al, , 1999Cherian et al, 2004). In contrast, iNOS expression is significantly induced by brain injury (Wada et al, 1998;Gahm et al, 2000;Petrov et al, 2000), resulting in a peak tissue NO concentration 1-2 days after TBI (Clark et al, 1996;Uzan et al, 2001). Pharmacological or genetic inhibition of NOS suggests a deleterious role for iNOS after TBI (Rinecker et al, 2003;Jones et al, 2004)-for example, specific inhibition of iNOS with aminoguanidine almost completely inhibits secondary contusion expansion following cold injury (Stoffel et al, 2000;Gahm et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

The Novel Nitric Oxide Synthase Inhibitor 4-amino-tetrahydro-L-biopterine Prevents Brain Edema Formation and Intracranial Hypertension following Traumatic Brain Injury in Mice

Terpolilli¹,

Zweckberger²,

Trabold³

et al. 2009

Journal of Neurotrauma

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Brain edema formation, resulting in increased intracranial pressure (ICP), is one of the most deleterious consequences of traumatic brain injury (TBI). Nitric oxide (NO) has previously been shown to be involved in the damage of the blood-brain barrier (BBB) and, thus, in the formation of post-traumatic brain edema; however, this knowledge never resulted in a clinically relevant therapeutic option because available NO synthase inhibitors have serious side effects in man. The aim of the current study was to investigate the therapeutic efficacy of VAS203, a novel tetrahydrobiopterine (BH3)-based NOS inhibitor, in experimental TBI. When added to isolated vessels rings obtained from rat basilar and middle cerebral arteries (n = 32-35) VAS203 showed the same vasoconstrictive effect as the classical NO synthase inhibitor L-(G)-nitro-arginine-methylester (L-NAME). VAS203 passed the BBB both in healthy and traumatized mouse brain (C57/BL6, n = 5 per group) and did not show any systemic side effects at therapeutic concentrations. When administered 30 min after experimental TBI (controlled cortical impact, 2.2 mg/kg/min i.v., n = 7 per group), VAS203 prevented any further increase in ICP or deterioration of cerebral blood flow. This effect was dose-dependent and long-lasting (i.e., 24 h after trauma, brain edema formation was still significantly reduced [-40%, p < 0.008; n = 7 per group] and functional improvements were present up to 7 days after TBI [p < 0.02 on post-trauma day 6; n = 8 per group]). Therefore, VAS203 may represent a promising candidate for the treatment of acute intracranial hypertension following TBI.

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Nitric Oxide (NO) metabolism in the cerebrospinal fluid of patients with severe head injury

Cited by 26 publications

References 45 publications

Oxidative Stress in Immature Brain after Traumatic Brain Injury

Oxidative Stress in Immature Brain after Traumatic Brain Injury

Cerebrospinal Fluid and Microdialysis Cytokines in Severe Traumatic Brain Injury: A Scoping Systematic Review

The Novel Nitric Oxide Synthase Inhibitor 4-amino-tetrahydro-L-biopterine Prevents Brain Edema Formation and Intracranial Hypertension following Traumatic Brain Injury in Mice

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