Mechanism of brain protection by nitroxide radicals in experimental model of closed-head injury

Renliang Zhang, Esther Shohami, Elie Beit-Yannai, Roman Bass, Victoria Trembovler, Amram Samuni

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Reactive oxygen-derived species were previously implicated in mediation of post-traumatic brain damage; however, the efficacy of traditional antioxidants in preventing/reversing the damage is sometimes limited. The present work focused on the mechanisms underlying the neuroprotective activity of cell permeable, nontoxic, anti-oxidants, namely stable nitroxide radicals in an experimental model of rat closed-head injury Brain damage was reduced by the weight-drop method and the clinical status was evaluated according to a neurological seventy score at I h and 24 h, where the difference between these scores reflects the extent of recovery. The metal chelator deferoxamine as well as three nitroxide derivatives, differing in hydrophilicity and charge, and one hydroxylamine (a reduced nitroxide) facilitated the clinical recovery and decreased the brain edema. The nitroxides, but neither the hydroxylamine nor deferoxamine, protected the integrity of the blood-brain barrier. Superoxide dismutase also improved the clinical recovery but did not affect brain edema or the blood-brain barrier. The results suggest that by switching back and forth between themselves, the nitroxide and hydroxylamine act catalytically as self-replenishing annoxidants, and protect brain tissue by terminating radical-chain reactions, oxidizing deleterious metal ions, and by removal of intracellular superoxide.

Original languageEnglish
Pages (from-to)332-340
Number of pages9
JournalFree Radical Biology and Medicine
Volume24
Issue number2
DOIs
StatePublished - 15 Jan 1998
Externally publishedYes

Keywords

  • Oxidative damage
  • Spin label
  • Superoxide
  • Transition metals
  • Traumatic brain injury

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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