DEXTRORPHAN REDUCES INFARCT VOLUME, VASCULAR INJURY, AND BRAIN EDEMA AFTER ISCHEMIC BRAIN INJURY

Focal cerebral ischemia confined to the cerebral cortex in the right m iddle cerebral artery (MCA) territory was induced by temporary ligatio n of the MCA and both common carotid arteries (CCAs), Reperfusion was initiated by releasing all three arterial occlusions after 90 min of i schemia, Infarct volume was morphometrically measured after triphenylt etrazolium chloride staining 24 h postischemia, Blood-brain barrier br eakdown was assessed 4 h postischemia by measuring vascular permeabili ty to fluorescein isothiocyanate-conjugated dextran (FITC-D), a macrom olecule tracer, Ischemic brain edema was measured based on percent wat er content, 24 h postischemia. Dextrorphan (DX) 20-40 mg/kg given ip 1 5 min before ischemia reduced infarct volume in a dose-dependent manne r with an apparent U-shaped dose-response curve; best protection was o bserved at 30 mg/kg, Posttreatment at 30 min, but not 60 min, was stil l effective, DX (30 mg/kg, given 15 min before ischemia) also reduced the postischemic increase in vascular permeability and brain edema in the right MCA cortex, Results from this study support the idea that NM DA receptor activation contributes to blood-brain barrier breakdown an d brain edema after ischemic insults.