Dietrich W D, Alonso O, Halley M, Busto R, Globus M Y
Department of Neurology, University of Miami School of Medicine, FL 33101.
Acta Neuropathol. 1992;84(6):621-9. doi: 10.1007/BF00227739.
The purpose of this study was to document the early cerebrovascular consequences of excessive N-methyl-D-aspartate (NMDA) receptor activation. Five microliters of NMDA (100 nmol/microliters) or vehicle was infused over a 15-min period into the lateral ventricle of adult rats. The protein tracer horseradish peroxidase (HRP) was injected intravenously for blood-brain barrier (BBB) studies. The intraventricular infusion of vehicle (n = 5) caused no alterations in arterial blood pressure or microvascular damage away from the intraventricular probe tract. In contrast, NMDA infusion (n = 8) led to a gradual increase in arterial blood pressure (mean 36 mm Hg). Multifocal regions of HRP extravasation were observed bilaterally throughout the neuraxis following NMDA infusion. Sites of BBB disruption and hemorrhage included brain regions bordering ventricular spaces. In addition, isolated foci of protein extravasation were commonly detected in the cerebral cortex, thalamus, basal forebrain, septum and cerebellum. Pretreatment with the noncompetitive NMDA antagonist MK-801 (2 mg/kg) substantially reduced the BBB responses to NMDA. However, microvascular abnormalities were seen in NMDA-infused rats where blood pressure elevations were inhibited by blood removal. In addition to neurons, cerebral blood vessels are also acutely affected by NMDA receptor activation. Blockage of NMDA receptor channels following brain injury may potentially provide protection by attenuating BBB breakdown and subsequent brain edema.
本研究的目的是记录过量N-甲基-D-天冬氨酸（NMDA）受体激活对早期脑血管的影响。将5微升NMDA（100纳摩尔/微升）或赋形剂在15分钟内注入成年大鼠的侧脑室。静脉注射蛋白质示踪剂辣根过氧化物酶（HRP）用于血脑屏障（BBB）研究。脑室内注入赋形剂（n = 5）未引起动脉血压改变或脑室探头通道以外的微血管损伤。相比之下，注入NMDA（n = 8）导致动脉血压逐渐升高（平均36毫米汞柱）。注入NMDA后，在整个神经轴双侧观察到HRP外渗的多灶性区域。血脑屏障破坏和出血部位包括与脑室空间相邻的脑区。此外，在大脑皮层、丘脑、基底前脑、隔区和小脑中通常检测到孤立的蛋白质外渗灶。用非竞争性NMDA拮抗剂MK-801（2毫克/千克）预处理可显著降低血脑屏障对NMDA的反应。然而，在通过放血抑制血压升高的NMDA注入大鼠中观察到微血管异常。除神经元外，脑血管也会受到NMDA受体激活的急性影响。脑损伤后阻断NMDA受体通道可能通过减轻血脑屏障破坏和随后的脑水肿提供保护。
