Antioxidant Therapies for Acute Spinal Cord Injury

Abstract

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.

Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury

“…The current therapeutic approach for SCI is limited to MP administration. The neuroproctective effects of MP has been proposed on the basis of inhibition of reactive nitrogen species peroxynitrite and its highly reactive free radicals [10,11]. The potent anti-inflammatory activity of MP suggest that neuroprotective effects and improvement of motor recovery in human SCI after of high-dose MP treatment is also due to its immunosuppressive properties [11,12].…”

“…The use of GC in the treatment of SCI has been proposed on the basis of the ability of high-dose MP to attenuate posttraumatic free radical-induced lipid peroxidation [10] or attenuation of oligodendrocyte apoptosis after injury [11]. However, the mechanisms by which GC protect the central nervous system are not completely understood.…”

High-dose ascorbic acid administration improves functional recovery in rats with spinal cord contusion injury

“…17 Free radicals and proinflammatory cytokines can cause a series of effects leading to progressive damage after SCI. 6,11 Free radicals not only attack and damage the membrane of neural cells, but also destroy the critical enzymatic systems in the phospholipid membrane, such as the activity of the Na þ -K þ -ATPase, resulting in swelling and dysfunction of neural cells, and ultimately their autolysis. 6 Physiologically, endogenous catalase and superoxide dismutase have functions that help clear free radicals.…”

“…8 On the basis of these observations, several exogenous antioxidants capable of scavenging free radicals have been proposed as a treatment regimen for SCI, with some exhibiting beneficial effects, such as ascorbic acid (AA) 9,10 and the nonglucocorticoid 21-aminosteroid tirilazad. 11 Among these antioxidants agents, AA is of particular interest because of its critical function in a wide range of physiological processes. 12 Several studies have investigated the therapeutic effect of AA administration on rat SCI models.…”

Prednisona e meloxicam no tratamento de ratos submetidos ao trauma agudo da medula espinhal

“…livres tem sido implicada como a maior causa de degeneração do sistema nervoso central (SNC) após o trauma (HALL, 2011), gerando um quadro de estresse oxidativo. O mais conhecido efeito deste estresse é a oxidação em todos os componentes celulares, principalmente os ácidos graxos insaturados da membrana, levando à peroxidação lipídica (BRAUND et al, 1990).…”