Antioxidant Therapies for Traumatic Brain Injury

Edward D. Hall, Radhika A. Vaishnav, Ayman G. Mustafa

Research output: Contribution to journalArticlepeer-review

323 Scopus citations

Abstract

Free radical-induced oxidative damage reactions, and membrane lipid peroxidation (LP), in particular, are among the best validated secondary injury mechanisms in preclinical traumatic brain injury (TBI) models. In addition to the disruption of the membrane phospholipid architecture, LP results in the formation of cytotoxic aldehyde-containing products that bind to cellular proteins and impair their normal functions. This article reviews the progress of the past three decades in regard to the preclinical discovery and attempted clinical development of antioxidant drugs designed to inhibit free radical-induced LP and its neurotoxic consequences via different mechanisms including the O2·- scavenger superoxide dismutase and the lipid peroxidation inhibitor tirilazad. In addition, various other antioxidant agents that have been shown to have efficacy in preclinical TBI models are briefly presented, such as the LP inhibitors U83836E, resveratrol, curcumin, OPC-14177, and lipoic acid; the iron chelator deferoxamine and the nitroxide-containing antioxidants, such as α-phenyl-tert-butyl nitrone and tempol. A relatively new antioxidant mechanistic strategy for acute TBI is aimed at the scavenging of aldehydic LP byproducts that are highly neurotoxic with "carbonyl scavenging" compounds. Finally, it is proposed that the most effective approach to interrupt posttraumatic oxidative brain damage after TBI might involve the combined treatment with mechanistically complementary antioxidants that simultaneously scavenge LP-initiating free radicals, inhibit LP propagation, and lastly remove neurotoxic LP byproducts.

Original languageEnglish
Pages (from-to)51-61
Number of pages11
JournalNeurotherapeutics
Volume7
Issue number1
DOIs
StatePublished - Jan 2010

Bibliographical note

Funding Information:
Portions of the work reviewed in this article were supported by funding from 5R01 NS046566, 5P30 NS051220, and 5P01 NS58484 and from the Kentucky Spinal Cord & Head Injury Research Trust.

Keywords

  • Traumatic brain injury
  • antioxidants
  • lipid peroxidation
  • oxidative damage

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Antioxidant Therapies for Traumatic Brain Injury'. Together they form a unique fingerprint.

Cite this