Salińska E, Pluta R, Puka M, Lazarewicz J W
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warszawa.
Exp Neurol. 1991 Apr;112(1):89-94. doi: 10.1016/0014-4886(91)90117-u.
To evaluate the participation of excitatory amino acid receptors sensitive to N-methyl-D-aspartate (NMDA) in ischemia-evoked redistribution of Ca2+ ions from the extra- to the intracellular compartment of the hippocampus, 2-amino-5-phosphonovalerate (APV), a specific antagonist of NMDA receptors, was administered to the rabbit hippocampus through a dialysis probe before, during, and after complete reversible 15-min cerebral ischemia. Microdialysis of the hippocampus allowed us to determine the changes in extracellular calcium and amino acid concentrations and to monitor the permeability of the blood-brain barrier (BBB) to fluorescein. Moreover, EEG and general physiological parameters were registered. APV significantly reduced the ischemic drop of calcium and increased the taurine and phosphoethanolamine content in the extracellular compartment, whereas changes in concentrations of other amino acids and BBB permeability were not modified. Local administration of APV also improved the recovery of EEG activity after ischemia. Inhibition by APV of ischemia-induced calcium redistribution in the hippocampus suggests a major role of NMDA receptors in the influx of calcium to hippocampal neurons during cerebral ischemia.
为评估对N-甲基-D-天冬氨酸（NMDA）敏感的兴奋性氨基酸受体在缺血诱发的海马体中钙离子从细胞外区室向细胞内区室重新分布过程中的作用，在完全可逆的15分钟脑缺血前、缺血期间及缺血后，通过透析探针将NMDA受体的特异性拮抗剂2-氨基-5-磷酸缬氨酸（APV）注入兔海马体。对海马体进行微透析使我们能够测定细胞外钙和氨基酸浓度的变化，并监测血脑屏障（BBB）对荧光素的通透性。此外，还记录了脑电图（EEG）和一般生理参数。APV显著减少了缺血引起的钙下降，并增加了细胞外区室中牛磺酸和磷酸乙醇胺的含量，而其他氨基酸浓度和血脑屏障通透性的变化未被改变。局部注射APV还改善了缺血后EEG活动的恢复。APV对缺血诱导的海马体中钙重新分布的抑制作用表明，NMDA受体在脑缺血期间钙离子流入海马神经元的过程中起主要作用。
