Robertson S C, Wetjen N M, Beer B J, Loftus C M
Division of Neurosurgery, University of Iowa College of Medicine, Iowa City 52242, USA.
J Neurosurg. 1997 Dec;87(6):927-33. doi: 10.3171/jns.1997.87.6.0927.
The authors studied the effects of pre- and postischemic administration of dizocilpine maleate (MK-801) on collateral and regional cerebral blood flow (CBF). The ischemic penumbra appears to benefit most from the neuroprotective effects of MK-801. The precise mechanism by which MK-801 provides this neuroprotection remains controversial. Alterations in CBF have been demonstrated with MK-801 administration, but whether the response is an increase or decrease in flow has remained unclear. A left-sided craniectomy was performed in 20 dogs. A branch of the middle cerebral artery (MCA) was cannulated and collateral blood supply-dependent tissue (CDT) was identified using the "shadow flow" technique. Regional CBF was measured using radiolabeled microspheres. Six dogs received MK-801 (1 mg/kg administered intravenously) before they underwent MCA branch occlusion; the remaining 14 dogs received MK-801 after they underwent MCA occlusion. Cerebral blood flow and vascular pressures were measured 30 and 60 minutes after MK-801 administration. In animals that received MK-801 before MCA occlusion, CBF did not change significantly from baseline values before or after occlusion. In contrast, in animals that received MK-801 after MCA occlusion, CBF was significantly reduced in all regions of the brain, including the CDT. Collateral blood supply-dependent tissue showed a 51.7% reduction in flow, whereas normal CBF was reduced by 29.7%. The MK-801 induced cerebral vasoconstriction in both groups. The neuroprotective effects of MK-801 do not appear to be caused by the augmentation of collateral or global cerebral circulation and, in fact, may block the glutamate-mediated vasodilation that occurs during ischemia.
作者研究了马来酸二氮卓西平（MK-801）缺血前后给药对侧支循环和局部脑血流量（CBF）的影响。缺血半暗带似乎最能从MK-801的神经保护作用中获益。MK-801提供这种神经保护的确切机制仍存在争议。已有研究表明，给予MK-801后CBF会发生改变，但血流是增加还是减少尚不清楚。对20只犬进行左侧颅骨切除术。将大脑中动脉（MCA）的一个分支插管，并使用“阴影血流”技术识别侧支血液供应依赖组织（CDT）。使用放射性标记微球测量局部CBF。6只犬在MCA分支闭塞前接受MK-801（静脉注射1mg/kg）；其余14只犬在MCA闭塞后接受MK-801。在给予MK-801后30分钟和60分钟测量脑血流量和血管压力。在MCA闭塞前接受MK-801的动物中，CBF在闭塞前后与基线值相比无显著变化。相比之下，在MCA闭塞后接受MK-801的动物中，包括CDT在内的大脑所有区域的CBF均显著降低。侧支血液供应依赖组织的血流减少了51.7%，而正常CBF减少了29.7%。两组中MK-801均诱导脑血管收缩。MK-801的神经保护作用似乎不是由侧支或全脑循环的增强引起的，事实上，它可能会阻断缺血期间发生的谷氨酸介导的血管舒张。
