MK-801 attenuates capillary bed compression and hypoperfusion following incomplete focal cerebral ischemia.
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 133Xe CBF, capillary diameter, and area of perfused vasculature. Capillary diameter increased from a control of 5.24 +/- 0.37 to 8.62 +/- 0.57 microns (p less than 0.001) and area of perfused vasculature from 20,943 +/- 1,151 to 30,442 +/- 1,691 microns2/x 10 magnification field (p less than 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.
Meyer
F B
FB
Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota 55905.
Anderson
R E
RE
Friedrich
P F
PF
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002196:Capillaries / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D011817:Rabbits
D016291:Dizocilpine Maleate