Effect of the NMDA antagonist MK-801 on local cerebral blood flow in focal cerebral ischaemia in the rat.
The effects of MK-801 upon local CBF after permanent middle cerebral artery (MCA) occlusion have been examined using [14C]iodoantipyrine autoradiography in halothane-anaesthetised rats. MK-801 (0.5 mg kg-1 i.v.) or saline was administered 30 min before MCA occlusion and CBF measured approximately 40 min after occlusion. In the hemisphere contralateral to the occluded MCA, MK-801 significantly reduced local CBF in 19 of the 22 regions examined from the levels in saline-treated rats. In the contralateral hemisphere, after treatment with MK-801, blood flow was reduced by an average of 37% with little variation in the magnitude of the reductions in different regions. In the hemisphere ipsilateral to MCA occlusion, MK-801 reduced CBF in almost every region located outside the territory of the occluded MCA. Within the territory of the occluded MCA, blood flow in the MK-801-treated rat did not significantly differ from values in vehicle-treated rats in any of the five cortical areas examined, although in the caudate nucleus there was a tendency for CBF to be lower in rats pretreated with MK-801. MK-801 had no effect on the amount of hypoperfused cerebral tissue (CBF less than 30 ml 100 g-1 min-1) in the ipsilateral hemisphere at any coronal plane examined; e.g., at coronal plane anterior 7.2 mm, 51 +/- 5% of the hemisphere displayed CBF of less than 30 ml 100 g-1 min-1 in saline-treated rats with MCA occlusion compared with 52 +/- 8% of the hemisphere in rats treated with MK-801 prior to MCA occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Park
C K
CK
Wellcome Surgical Institute, University of Glasgow, Scotland.
Nehls
D G
DG
Teasdale
G M
GM
McCulloch
J
J
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D008297:Male; D016202:N-Methylaspartate; D051381:Rats; D011919:Rats, Inbred Strains
D003986:Dibenzocycloheptenes; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate