Effects of dextromethorphan on rat brain during ischemia and reperfusion assessed by magnetic resonance spectroscopy.
Using proton and phosphorus magnetic resonance spectroscopy, we evaluated the metabolic effects of preischemic administration of the N-methyl-D-aspartate antagonist dextromethorphan (50 mg/kg i.p.) during global forebrain ischemia and subsequent reperfusion in rats. Dextromethorphan-treated animals (n = 10) showed less lactate formation during ischemia than untreated animals (n = 11, p less than 0.001). During reperfusion, the lactate level in the treated group was reduced (p less than 0.05). Tissue pH declined less in the treated group during ischemia (p less than 0.01). There was no difference in the phosphocreatine/inorganic phosphate peak height ratio between groups. During ischemia, the N-acetylaspartate resonance peaks decreased in both groups. Histologic damage assessed in the hippocampal CA1 region 7 days after the ischemic insult was more severe in the untreated group (p less than 0.05). There was a significant correlation between end-ischemic tissue pH and hippocampal damage (r = -0.73, p less than 0.05). In the dextromethorphan-treated animals, 90% of the rats survived compared with 47% of the untreated animals (p less than 0.05). These results support findings in previous studies that dextromethorphan attenuates ischemic damage.
van Rijen
P C
PC
Department of Neurosurgery, State University Hospital Utrech, The Netherlands.
Verheul
H B
HB
van Echteld
C J
CJ
Balázs
R
R
Lewis
P
P
Nasim
M M
MM
Tulleken
C A
CA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003915:Dextromethorphan / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D007773:Lactates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion
D007773:Lactates; D003915:Dextromethorphan