Brain Hydroxyl Radical Generation in Acute Experimental Head Injury

Edward D. Hall, Paula K. Andrus, Patricia A. Yonkers

Research output: Contribution to journalReview articlepeer-review

228 Scopus citations


Abstract: The time course and intensity of brain hydroxyl radical (OH) generation were examined in male CF‐1 mice during the first hour after moderate or severe concussive head injury. Hydroxyl radical production was measured using the salicylate trapping method in which the production of 2,3‐ and/or 2,5‐dihydroxybenzoic acid (DHBA) in brain 15 min after salicylate administration was used as an index of OH formation. In mice injured with a concussion of moderate severity as defined by the 1‐h posttraumatic neurologic recovery (grip score), a 60% increase in 2,5‐DHBA formation was observed by 1 min after injury compared with that observed in uninjured mice. The peak in DHBA formation occurred at 15 min after injury (+67.5%; p < 0.02, compared with uninjured). At 30 min, the increase in DHBA lost significance, indicating that the posttraumatic increase in brain OH formation is a transient phenomenon. In severely injured mice, the peak increase in DHBA (both 2,3‐ and 2,5‐) was observed at 30 min after injury, but also fell off thereafter as with the moderate injury severity. Preinjury dosing of the mice with SKF‐525A (50 mg/kg i.p.), an inhibitor of microsomal drug oxidations, did not blunt the posttraumatic increase in salicylate‐derived 2,5‐DHBA, thus showing that it is not due to increased metabolic hydroxylation. Neither injury nor SKF‐525A administration affected the DHBA plasma levels. However, saline perfusion of the injured mice to remove the intravascular blood before brain removal eliminated the injury‐induced increase in 2,5‐DHBA, but did not affect the baseline levels seen in uninjured mice. This implies that the source of the increased DHBA in the injured mice is the microvasculature, probably the endothelium. The administration of the 21‐aminosteroid lipid antioxidant, tirilazad mesylate, which possesses OH scavenging properties, also attenuated the posttraumatic increase in DHBA, further supporting that it reflects an increase in OH radical formation. These results are the first direct demonstration of the occurrence and time course of increased OH production in injured brain.

Original languageEnglish
Pages (from-to)588-594
Number of pages7
JournalJournal of Neurochemistry
Issue number2
StatePublished - Feb 1993


  • Brain
  • Concussion
  • Hydroxyl radical
  • Salicylate trapping

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Brain Hydroxyl Radical Generation in Acute Experimental Head Injury'. Together they form a unique fingerprint.

Cite this