Validation of brain extracellular glycerol as an indicator of cellular membrane damage due to free radical activity after traumatic brain injury

Amedeo Merenda, Marinella Gugliotta, Rebecca Holloway, Joseph E. Levasseur, Beht Alessandri, Dong Sun, M. Ross Bullock

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Following severe traumatic brain injury (TBI), increasing oxygen delivery to the brain has been advocated as a useful strategy to reverse mitochondrial dysfunction and improve neurological outcome. However, this might also promote overproduction of free radicals, responsible for lipid peroxidation and hence brain cell damage. Therefore, a method for monitoring this potential adverse effect in humans is desirable. Glycerol, an end product of phospholipid breakdown, easily detectable in the human brain by means of microdialysis, might represent a reliable indicator of free radical-induced cell membrane damage. Brain microdialysates were collected from 24 adult male Sprague-Dawley rats over a 3-hour period following sham operation (n = 6), chemical brain injury via administration of Fenton's reagent (n = 6), a powerful hydroxyl radical generator, and lateral fluid percussion injury (FPI; n = 12). In the FPI animals, post-traumatic i.v. administration of either normal saline or the free radical scavenger Tempol (10 mg/kg, followed by an infusion of 30 mg/kg/h over 3 h) was carried out to evaluate the effect of blockade of free radical generation. Samples were analyzed for the presence of glycerol and the marker of hydroxyl radical (OH·) by generation of 2,3-DHBA (dihydroxybenzoic acid). Brain tissue staining with TTC (2,3,5-triphenyltetrazoium chloride) was performed for lesion size assessment. Rats subjected to either Fenton's reagent administration or FPI exhibited significantly higher levels of glycerol as compared with shams (p = 0.05). However, when the FPI was followed by Tempol administration, concentration of both glycerol and 2,3-DHBA decreased significantly (p = 0.05). Furthermore, TCC staining revealed a significant reduction of secondary brain tissue damage in Tempol-treated animals (p = 0.05). Our data suggest that injury-induced increases in microdialysate glycerol levels are a valid indicator of free radical activity, and their amelioration following Tempol treatment accords with less histological damage in response to FPI.

Original languageEnglish (US)
Pages (from-to)527-537
Number of pages11
JournalJournal of neurotrauma
Volume25
Issue number5
DOIs
StatePublished - May 1 2008
Externally publishedYes

Keywords

  • Adult brain injury
  • Axonal injury
  • Head trauma
  • Metabolism
  • Microdialysis

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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