Wahlestedt C, Golanov E, Yamamoto S, Yee F, Ericson H, Yoo H, Inturrisi C E, Reis D J
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021.
Nature. 1993 May 20;363(6426):260-3. doi: 10.1038/363260a0.
The excitatory amino acid, L-glutamate, acting through its N-methyl-D-aspartate (NMDA) receptor, may contribute to neuronal death following cerebral vascular occlusion. In support of this hypothesis, NMDA receptor antagonists reduce the volume of infarction produced by occlusion of the middle cerebral artery in vivo and attenuate Ca2+ influx and neuronal death elicited by L-glutamate or NMDA in vitro. A complementary DNA coding for a major component of the NMDA receptor channel complex, a single protein of M(r) 105.5K (NMDA-R1), has been isolated from rat brain. Here we demonstrate that inhibition of the synthesis of NMDA-R1 by treatment with antisense oligodeoxynucleotides selectively reduces the expression of NMDA receptors, prevents the neurotoxicity elicited by NMDA in vitro and reduces the volume of the focal ischaemic infarction produced by occlusion of the middle cerebral artery in the rat.
兴奋性氨基酸L-谷氨酸通过其N-甲基-D-天冬氨酸（NMDA）受体发挥作用，可能在脑血管闭塞后导致神经元死亡。支持这一假说的证据是，NMDA受体拮抗剂可在体内减少大脑中动脉闭塞所产生的梗死体积，并在体外减弱由L-谷氨酸或NMDA引起的Ca2+内流和神经元死亡。已从大鼠脑中分离出一种编码NMDA受体通道复合物主要成分的互补DNA，该复合物是一种分子量为105.5K的单一蛋白质（NMDA-R1）。在此我们证明，用反义寡脱氧核苷酸处理抑制NMDA-R1的合成，可选择性降低NMDA受体的表达，防止NMDA在体外引起的神经毒性，并减少大鼠大脑中动脉闭塞所产生的局灶性缺血性梗死体积。
