A Review of the Effectiveness of Antioxidant Therapy to Reduce Neuronal Damage in Acute Traumatic Brain Injury

Rigg, John L.; Elovic, Elie P.; Greenwald, Brian D.

doi:10.1097/00001199-200507000-00010

Cited by 17 publications

(16 citation statements)

References 14 publications

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“…Thus, the relationship between oxidative stress and TBI has generated considerable interest in the development of antioxidant therapies for neuroprotection. However, despite promising results in the treatment of TBI in animal models, evidence of successful antioxidant therapy in TBI patients is limited [7] . In addition, there are a number of drawbacks to the use of exogenous antioxidants for treatment, as many antioxidants do not efficiently cross the bloodbrain barrier (BBB), are rather unstable in the body, have short therapeutic time windows, and should be given in a very narrow range of therapeutic dosages owing to their toxicity at high doses [7,8] .…”

Section: Introductionmentioning

confidence: 99%

“…However, despite promising results in the treatment of TBI in animal models, evidence of successful antioxidant therapy in TBI patients is limited [7] . In addition, there are a number of drawbacks to the use of exogenous antioxidants for treatment, as many antioxidants do not efficiently cross the bloodbrain barrier (BBB), are rather unstable in the body, have short therapeutic time windows, and should be given in a very narrow range of therapeutic dosages owing to their toxicity at high doses [7,8] . Hence, alternative therapeutic approaches are needed to inhibit the detrimental effects of ROS, for instance, through the induction of endogenous enzymatic antioxidants.…”

Section: Introductionmentioning

confidence: 99%

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The role of Nrf2 signaling in the regulation of antioxidants and detoxifying enzymes after traumatic brain injury in rats and mice

et al. 2010

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Aim: To determine whether Nrf2 signaling pathway activation could attenuate oxidative stress and neuronal damage following traumatic brain injury (TBI). Methods: Controlled cortical impact (CCI) injury was performed in Sprague-Dawley rats and Nrf2-knockout or control mice. Sulforaphane (SFN), a potent Nrf2 activator, was used to activate Nrf2. Oxidative stress, lesion volume, neuron degeneration, and neurologic dysfunction were determined using biochemical, histopathological and neuroethologic approaches. Protein and mRNA levels of Nrf2 and the antioxidant enzymes heme oxygenase 1 (HO-1) and NAD(P)H:quinine oxidoreductase 1 (NQO1) were assessed using Western blot analysis and RT-PCR. Results: Activation of Nrf2 by SFN( 5 mg/kg, ip) induced the nuclear translocation and activation of Nrf2, which resulted in an up-regulation of Nrf2-dependent antioxidant enzymes and a reduction of oxidative damage after TBI. In accordance with these biochemical changes, SFN also significantly reduced neuronal death, contusion volume, and neurological dysfunction after TBI. Furthermore, Nrf2-knockout mice showed more severe oxidative stress and neurologic deficits after TBI and did not benefit from the effects of SFN. Conclusion: Nrf2 plays a pivotal role in cell defenses against the oxidative stress of TBI. In addition, pharmacological activation of the Nrf2 signaling pathway by small molecule inducers such as SFN attenuated oxidative stress and neuronal damage following TBI.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of Nrf2 signaling in the regulation of antioxidants and detoxifying enzymes after traumatic brain injury in rats and mice

et al. 2010

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“…Unfortunately, these findings have not directly translated to the clinical situation [125,126]. Unfortunately, these findings have not directly translated to the clinical situation [125,126].…”

Section: Antioxidant Therapy For Traumatic Brain Injurymentioning

confidence: 99%

Antioxidants and Free Radical Scavengers for the Treatment Of Stroke, Traumatic Brain Injury and Aging

Slemmer

Shacka²,

Sweeney³

et al. 2008

CMC

338

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The overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a common underlying mechanism of many neuropathologies, as they have been shown to damage various cellular components, including proteins, lipids and DNA. Free radicals, especially superoxide (O(2)*-), and non-radicals, such as hydrogen peroxide (H(2)O(2)), can be generated in quantities large enough to overwhelm endogenous protective enzyme systems, such as superoxide dismutase (SOD) and reduced glutathione (GSH). Here we review the mechanisms of ROS and RNS production, and their roles in ischemia, traumatic brain injury and aging. In particular, we discuss several acute and chronic pharmacological therapies that have been extensively studied in order to reduce ROS/RNS loads in cells and the subsequent oxidative stress, so-called "free-radical scavengers." Although the overall aim has been to counteract the detrimental effects of ROS/RNS in these pathologies, success has been limited, especially in human clinical studies. This review highlights some of the recent successes and failures in animal and human studies by attempting to link a compound's chemical structure with its efficacy as a free radical scavenger. In particular, we demonstrate how antioxidants derived from natural products, as well as long-term dietary alterations, may prove to be effective scavengers of ROS and RNS.

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“…Despite the promising results in the treatment of TBI in animal models, evidence of successful antioxidant therapy in clinical practice is limited [143]. There are a number of drawbacks to the use of exogenous antioxidants, for example, the limited penetrability through the BBB, the rapid metabolism and instability of these compounds, short therapeutic windows, and a very narrow therapeutic dosage range, resulting in toxicity at higher doses [143, 144]. Despite these limitations, natural antioxidants and modified antioxidants are promising candidates for future drugs to treat TBI.…”

Section: Antioxidant Strategies For Neuroprotectionmentioning

confidence: 99%

Perspectives on Molecular Biomarkers of Oxidative Stress and Antioxidant Strategies in Traumatic Brain Injury

Arent

Souza

Walz

et al. 2014

BioMed Research International

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Traumatic brain injury (TBI) is frequently associated with abnormal blood-brain barrier function, resulting in the release of factors that can be used as molecular biomarkers of TBI, among them GFAP, UCH-L1, S100B, and NSE. Although many experimental studies have been conducted, clinical consolidation of these biomarkers is still needed to increase the predictive power and reduce the poor outcome of TBI. Interestingly, several of these TBI biomarkers are oxidatively modified to carbonyl groups, indicating that markers of oxidative stress could be of predictive value for the selection of therapeutic strategies. Some drugs such as corticosteroids and progesterone have already been investigated in TBI neuroprotection but failed to demonstrate clinical applicability in advanced phases of the studies. Dietary antioxidants, such as curcumin, resveratrol, and sulforaphane, have been shown to attenuate TBI-induced damage in preclinical studies. These dietary antioxidants can increase antioxidant defenses via transcriptional activation of NRF2 and are also known as carbonyl scavengers, two potential mechanisms for neuroprotection. This paper reviews the relevance of redox biology in TBI, highlighting perspectives for future studies.

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A Review of the Effectiveness of Antioxidant Therapy to Reduce Neuronal Damage in Acute Traumatic Brain Injury

Cited by 17 publications

References 14 publications

The role of Nrf2 signaling in the regulation of antioxidants and detoxifying enzymes after traumatic brain injury in rats and mice

The role of Nrf2 signaling in the regulation of antioxidants and detoxifying enzymes after traumatic brain injury in rats and mice

Antioxidants and Free Radical Scavengers for the Treatment Of Stroke, Traumatic Brain Injury and Aging

Perspectives on Molecular Biomarkers of Oxidative Stress and Antioxidant Strategies in Traumatic Brain Injury

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