Neuroprotective profile of dextromethorphan in an experimental model of penetrating ballistic-like brain injury

Deborah A. Shear*, Anthony J. Williams, Keith Sharrow, Xi Chun M. Lu, Frank C. Tortella

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Dextromethorphan (DM) has been well-characterized as a neuroprotective agent in experimental models of CNS injury. The goal of this study was to determine the neuroprotective profile of DM in a military-relevant model of penetrating ballistic-like brain injury (PBBI). In an acute (3 day) dose-response study, anesthetized male Sprague-Dawley rats were exposed to a unilateral frontal PBBI with DM (0.156-10 mg/kg) or vehicle delivered as an i.v. bolus from 30 min to 48 h post-injury. In a follow-up (7 day) experiment, the 10-mg/kg bolus injections of DM were administered in conjunction with a 6-h infusion (5 mg/kg/h). DM bolus injections alone produced a dose-dependent improvement in motor recovery on a balance beam task at 3 days post-injury. However, more rapid recovery (24 h) was observed on this task when the bolus injections were combined with the 6-h infusion. Moreover, the DM bolus/infusion treatment regimen resulted in a significant (76%) improvement in cognitive performance in a novel object recognition (NOR) task at 7 days post-injury. Although post-injury administration of DM (all doses) failed to reduce core lesion size, the maximum dose of DM (10 mg/kg) was effective in reducing silver-stained axonal fiber degeneration in the cortical regions adjacent to the injury.

Original languageEnglish
Pages (from-to)56-62
Number of pages7
JournalPharmacology, Biochemistry and Behavior
Issue number1
StatePublished - Nov 2009
Externally publishedYes


  • Cognitive
  • DM
  • Dextromethorphan
  • Motor
  • NOR
  • Novel object recognition
  • PBBI
  • Penetrating ballistic-like brain injury
  • TBI
  • Traumatic brain injury


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