Dextrorphan reduces infarct volume, vascular injury, and brain edema after ischemic brain injury.
Focal cerebral ischemia confined to the cerebral cortex in the right middle cerebral artery (MCA) territory was induced by temporary ligation of the MCA and both common carotid arteries (CCAs). Reperfusion was initiated by releasing all three arterial occlusions after 90 min of ischemia. Infarct volume was morphometrically measured after triphenyltetrazolium chloride staining 24 h postischemia. Blood-brain barrier breakdown was assessed 4 h postischemia by measuring vascular permeability to fluorescein isothiocyanate-conjugated dextran (FITC-D), a macromolecule tracer. Ischemic brain edema was measured based on percent water content, 24 h postischemia. Dextrorphan (DX) 20-10 mg/kg given ip 15 min before ischemia reduced infarct volume in a dose-dependent manner with an apparent U-shaped dose-response curve; best protection was observed at 30 mg/kg. Posttreatment at 30 min, but not 60 min, was still 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 NMDA receptor activation contributes to blood-brain barrier breakdown and brain edema after ischemic insults
Du
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C
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hu
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R
Hsu
C Y
CY
Choi
D W
DW
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002245:Carbon Dioxide / Q000097:blood; D017536:Carotid Artery, Common; D002544:Cerebral Infarction / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation; D003917:Dextrorphan / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D051381:Rats; D015424:Reperfusion; D013997:Time Factors
D001786:Blood Glucose; D018696:Neuroprotective Agents; D003917:Dextrorphan; D002245:Carbon Dioxide; D010100:Oxygen