Friedrich, Patricia F.

The effects of the N-methyl-d-aspartate (NMDA) antagonist MK-801 on capillary beds and CBF following 1 h of transient incomplete focal cerebral ischemia were studied by examining 133 Xe CBF, capillary diameter, and area of perfused vasculature. Capillary diameter increased from a control of 5.24 ± 0.37 to 8.62 ± 0.57 μm (p < 0.001) and area of perfused vasculature from 20,943 ± 1,151 to 30,442 ± 1,691 μm 2 /×10 magnification field (p < 0.001) with MK-801 1.0 mg/kg administered 30 min prior to ischemia. After flow restoration in control animals, there was a relative hypoperfusion with eventual normalization of CBF over 60 min. Alternatively, in MK-801 1.0 mg/kg animals, there was rapid normalization of CBF upon flow restoration without the postischemic hypoperfusion observed in controls. On histological analysis, there was consistently less neuronal edema in MK-801-treated animals. These results support the hypothesis that hypoperfusion following incomplete focal cerebral ischemia may be due in part to NMDA-mediated cellular edema with subsequent extravascular capillary bed compression.