The presence of 4-hydroxynonenal/protein complex as an indicator of oxidative stress after experimental spinal cord contusion in a rat model

Baldwin, Stanley A.; Broderick, Richard W.; Osbourne, David; Waeg, Georg; Blades, Deborah A.

doi:10.3171/jns.1998.88.5.0874

Cited by 54 publications

(28 citation statements)

References 45 publications

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“…The accumulation of protein-bound HNE, which was demonstrated by previous reports in rat spinal cord injury (8,9), was also evident in this guinea pig SCI model, in both the injury site (T10-T11) and adjacent segments (T8-T9 and T12-T13) (Fig. 2).…”

Section: Resultssupporting

confidence: 63%

“…Therefore, these byproducts of lipid peroxidation have been postulated to be involved in the pathogenesis of spinal cord injury (5,7). Such hypothesis was supported by the findings that tissue levels of HNE have also been shown to be increased after spinal cord injury (SCI) (8,9). However, similar measurements of acrolein in SCI have not accomplished.…”

Section: Introductionmentioning

confidence: 93%

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Accumulation of Acrolein–Protein Adducts after Traumatic Spinal Cord Injury

2005

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Reactive oxygen species and resultant lipid peroxidation (LPO) have been associated with central nervous system trauma. Acrolein (2-propenal) and 4-hydroxynonenal (HNE) are the most toxic byproducts of LPO, with detrimental effects in various types of cells. In this study, we used immunoblotting techniques to detect the accumulation of protein-bound acrolein and HNE. We report that protein-bound acrolein and HNE were significantly increased in guinea pig spinal cord following a controlled compression injury. The acrolein and HNE protein-adducts increased in the damaged spinal cord as early as 4 h after injury, reached a peak at 24 h after injury, and remained at a significantly high level up to 7 days after injury. Such increase of protein adducts was also observed in the adjacent segments of the injury site beginning at 24 h post injury. These results suggest that products of lipid peroxidation, especially acrolein, may play a critical role in the secondary neuronal degeneration, which follows mechanical insults.

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Section: Resultssupporting

confidence: 63%

Section: Introductionmentioning

confidence: 93%

Accumulation of Acrolein–Protein Adducts after Traumatic Spinal Cord Injury

2005

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“…However, subsequent studies using one of the more contemporary rat contusion SCI paradigms and more sensitive immunoblotting of the immunohistochemical assay methods have more completely and specifically defined the time course of LP (4-HNE, acrolein) and protein oxidation (protein carbonyl), and nitration (3-NT) following SCI. The first of these showed a peak increase in 4-HNE immunostaining at 24 h [21] or 48 h [20] after SCI. A more recent and more extended immunoblotting/immunohistochemical time course study in the rat contusion model has confirmed that the increase in 4-HNE occurs as early as 1 h, peaks at 24 h, and remains significantly elevated for at least 7 days [23].…”

Section: Onset and Duration Of Oxidative Damage In The Injured Spinalmentioning

confidence: 99%

“…An increase in LP that appears in the injured cord within the first hour has also been evidenced in terms of a depletion of endogenous antioxidants, including ascorbic acid [16], alpha-tocopherol (also known as vitamin E) [17], glutathione [18], and ubiquinol-9 and ubiqunol-10 [19]. More contemporary immunohistochemical and immunoblotting methods have been recently used, which reveals an impressive increase in the levels of the LP-derived aldehydic breakdown products 4-HNE [20][21][22][23] and acrolein [24,25].…”

Section: Increased Lipid Peroxidationmentioning

confidence: 99%

Antioxidant Therapies for Acute Spinal Cord Injury

2011

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Summary:One of the most investigated molecular mechanisms involved in the secondary pathophysiology of acute spinal cord injury (SCI) is free radical-induced, iron-catalyzed lipid peroxidation (LP) and protein oxidative/nitrative damage to spinal neurons, glia, and microvascular cells. The reactive nitrogen species peroxynitrite and its highly reactive free radicals are key initiators of LP and protein nitration in the injured spinal cord, the biochemistry, and pathophysiology of which are first of all reviewed in this article. This is followed by a presentation of the antioxidant mechanistic approaches and pharmacological compounds that have been shown to have neuroprotective properties in preclinical SCI models. Two of these, which act by inhibition of LP, are high-dose treatment with the glucocorticoid steroid methylprednisolone (MP) and the nonglucocorticoid 21-aminosteroid tirilazad, have been demonstrated in the multicenter NASCIS clinical trials to produce at least a modest improvement in neurological recovery when administered within the first 8 hours after SCI. Although these results have provided considerable validation of oxidative damage as a clinically practical neuroprotective target, there is a need for the discovery of safer and more effective antioxidant compounds for acute SCI.

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“…The role of reactive oxygen-induced oxidative damage to spinal cord lipids (i.e., lipid peroxidation, LP) and proteins following acute spinal cord injury (SCI) has been strongly supported in previous work (Aksenova et al, 2002; Baldwin et al, 1998; Braughler and Hall, 1989; Hall and Braughler, 1993; Juurlink and Paterson, 1998; Springer et al, 1997). Earlier investigations attributed much of the post-traumatic oxidative damage to the reactive oxygen species (ROS) hydrogen peroxide (H 2 O 2 ) and its derived hydroxyl radical (•OH) formed rapidly by iron-dependent Fenton reactions (Braughler and Hall, 1989).…”

Section: Introductionmentioning

confidence: 82%

Temporal and Spatial Dynamics of Peroxynitrite-Induced Oxidative Damage After Spinal Cord Contusion Injury

Carrico

Vaishnav²,

Hall³

2009

Journal of Neurotrauma

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The reactive nitrogen species peroxynitrite (PN) has been suggested to be an important mediator of the secondary oxidative damage that occurs following acute spinal cord injury (SCI). The PN decomposition products nitrogen dioxide (•NO2), hydroxyl radical (•OH), and carbonate radical (•CO3) are highly reactive with cellular lipids and proteins. In this immunohistochemical study, we examined the temporal (3, 24, and 72 h, and 1 and 2 weeks) and spatial relationships of PN-mediated oxidative damage in the contusion-injured rat thoracic spinal cord (IH device, 200 kdyn, T10) using 3-nitrotyrosine (3-NT), a marker for protein nitration by PN-derived •NO2 and 4-hydroxynonenal (4-HNE), an indicator of lipid peroxidation (LP) initiated by any of the PN radicals. Minimal 3-NT or 4-HNE immunostaining was seen in sham, non-injured spinal cords. In contrast, both markers showed a substantial increase at 3 h post-injury at the epicenter, that extended throughout the gray matter and into the surrounding white matter. At 24 and 72 h, the oxidative damage expanded circumferentially to involve all but a small rim of white matter tissue at the injury site, and longitudinally as much as 6–9 mm in the rostral and caudal directions. The staining was observed in neuronal soma, axons, and microvessels. At all time points except 3 h, there was no significant difference in the mean rostral or caudal extent of 3-NT and 4-HNE staining. By 1, and more so at 2 weeks, the longitudinal extent of the oxidative damage staining was greatly decreased. The spatial and temporal overlap of 3-NT and 4-HNE staining supports the concept that PN is involved in both damage produced by lipid peroxidation and protein nitration, and that antioxidant agents that target PN or PN-derived radicals should be effective neuroprotectants for acute SCI if administered during the first post-injury hours.

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The presence of 4-hydroxynonenal/protein complex as an indicator of oxidative stress after experimental spinal cord contusion in a rat model

Cited by 54 publications

References 45 publications

Accumulation of Acrolein–Protein Adducts after Traumatic Spinal Cord Injury

Accumulation of Acrolein–Protein Adducts after Traumatic Spinal Cord Injury

Antioxidant Therapies for Acute Spinal Cord Injury

Temporal and Spatial Dynamics of Peroxynitrite-Induced Oxidative Damage After Spinal Cord Contusion Injury

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