Antioxidant Therapies for Acute Spinal Cord Injury

Edward D. Hall

Research output: Contribution to journalReview articlepeer-review

159 Scopus citations

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.

Original languageEnglish
Pages (from-to)152-167
Number of pages16
JournalNeurotherapeutics
Volume8
Issue number2
DOIs
StatePublished - Apr 2011

Bibliographical note

Funding Information:
Full conflict of interest disclosure is available in the for this article. Some of the work reviewed in this aricle was supported by grants from the Kentucky Spinal Cord & Head Injury Research Trust.

Keywords

  • Spinal cord injury
  • antioxidants
  • free radicals
  • lipid peroxidation
  • neuroprotection
  • peroxynitrite

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

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