Glucocorticoid mechanisms in acute spinal cord injury: A review and therapeutic rationale

Hall, Edward D.; Braughler, J M

doi:10.1016/0090-3019(82)90140-9

Cited by 225 publications

(79 citation statements)

References 45 publications

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“…Attention was focused on the hypothetical possibility that glucocorticoid steroids might be effective inhibitors of post-traumatic LP, based on their high lipid solubility and known ability to intercalate into artificial membranes between the hydrophobic polyunsaturated fatty acids of the membrane phospholipids and to thereby limit the propagation of LP chain reactions throughout the phospholipid bilayer [57,[72][73][74]. The author's laboratory tested whether the early administration of high-dose glucocorticoid MP might be able to inhibit post-traumatic spinal cord LP.…”

Section: Antioxidant Neuroprotection With High-dose Methylprednisolonmentioning

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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Section: Antioxidant Neuroprotection With High-dose Methylprednisolonmentioning

confidence: 99%

Antioxidant Therapies for Acute Spinal Cord Injury

2011

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“…Early studies demonstrated a Duration of lipid peroxidation after acute spinal cord injury in rats and the effect of methylprednisolone Laboratory investigation significant biochemical effect after the administration of high-dose methylprednisolone. [8][9][10][21][22][23][24]37 The potential for human application of this treatment led to the development of the National Acute Spinal Cord Injury Studies.…”

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confidence: 99%

Duration of lipid peroxidation after acute spinal cord injury in rats and the effect of methylprednisolone

Christie

Comeau²,

Myers³

et al. 2008

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Object Oxidative stress leading to lipid peroxidation is a major cause of secondary injury following spinal cord injury (SCI). The objectives of this study were to determine the duration of lipid peroxidation following acute SCI and the efficacy of short-and long-term administration of methylprednisolone on decreasing lipid peroxidation. Methods A total of 226 female Wistar rats underwent clip-compression induced SCI. In the first part of the study, spinal cords of untreated rats were assayed colorimetrically for malondialdehyde (MDA) to determine lipid peroxidation levels at various time points between 0 and 10 days. In the second part of the study, animals were treated with methylprednisolone for either 24 hours or 7 days. Control animals received equal volumes of normal saline. Treated and control rats were killed at various time points between 0 and 7 days. Results The MDA levels initially peaked 4 hours postinjury. By 12 hours, the MDA levels returned to baseline. A second increase was observed from 24 hours to 5 days. Both peak values differed statistically from the trough values (p < 0.008). The methylprednisolone reduced MDA levels (p < 0.04) within 12 hours of injury. No effect was seen at 24 hours or later. Conclusions The results of this study indicate that oxidative stress persists for 5 days following SCI in rats, and although methylprednisolone reduces MDA levels within the first 12 hours, it has no effect on the second lipid peroxidation peak.

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“…In the early 1980's, beneficial effects of intravenous methylprednisolone (30 mg/kg) on experimental SCI have been confirmed (Hall & Braughler, 1982, Braughler & Hall, 1983, Laschinger et al, 1984. It has been believed that steroid act as cellular and lysosomal membrane stabilizers.…”

Section: Steroidmentioning

confidence: 96%