Effect of the NMDA Antagonist MK-801 on Local Cerebral Blood Flow in Focal Cerebral Ischaemia in the Rat

Abstract

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 ∼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 −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 −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. Thus, the reported antiischaemic effects of MK-801 in this model cannot be attributed to improvement of blood flow to the hypoperfused cerebral tissue.