Neuroprotective profile of dextromethorphan in an experimental model of penetrating ballistic-like brain injury.
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.
Shear
Deborah A
DA
Walter Reed Army Institute of Research, Department of Applied Neurobiology, Silver Spring, MD 21045, USA. Deborah.Shear@AMEDD.ARMY.MIL
Williams
Anthony J
AJ
Sharrow
Keith
K
Lu
Xi-Chun M
XC
Tortella
Frank C
FC
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D003071:Cognition / Q000187:drug effects; D003915:Dextromethorphan / Q000008:administration & dosage / Q000627:therapeutic use*; D020833:Diffuse Axonal Injury / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000293:injuries* / Q000601:surgery; D020197:Head Injuries, Penetrating / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D007091:Image Processing, Computer-Assisted; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D013997:Time Factors
D018696:Neuroprotective Agents; D003915:Dextromethorphan