Zuccarello M, Anderson D K
Veterans Administration Medical Center, Cincinnati, Ohio.
J Neurotrauma. 1993 Winter;10(4):397-403. doi: 10.1089/neu.1993.10.397.
Excitatory amino acids and oxygen free radicals have been reported to cooperate in the genesis of brain injury in vivo and in vitro. In this study, we tested the capacity of a noncompetitive N-methyl-D-aspartate receptor antagonist, MK-801, and a 21-aminosteroid, U-74006F, tirilazad mesylate, to block the opening of the blood-brain barrier after subarachnoid injection of FeCl2, which is believed to cause a primarily "pure" free radical insult. Subarachnoid injection of FeCl2 resulted in a significant 10-fold increase in Evans blue extravasation while sham injection or NaCl injection had no effect. Pretreatment with either MK-801 or U-74006F significantly reduced the FeCl2-induced increase in capillary permeability by 43 and 63%, respectively (p < 0.05). Combined treatment with MK-801 and U-74006F resulted in a 65% reduction in vascular leakage that was not significantly greater than pretreatment with either drug alone. These results show that both excitatory amino acids and free radicals can damage the cerebral microvasculature and that an excitatory amino acid antagonist can partially protect the blood-brain barrier after free radical-induced injury.
据报道，兴奋性氨基酸和氧自由基在体内和体外脑损伤的发生过程中相互作用。在本研究中，我们测试了一种非竞争性N-甲基-D-天冬氨酸受体拮抗剂MK-801和一种21-氨基类固醇甲磺酸盐替拉扎德（U-74006F）在蛛网膜下腔注射氯化铁后阻断血脑屏障开放的能力，据信氯化铁主要引起“单纯”的自由基损伤。蛛网膜下腔注射氯化铁导致伊文思蓝外渗显著增加10倍，而假注射或注射氯化钠则无影响。用MK-801或U-74006F预处理分别使氯化铁诱导的毛细血管通透性增加显著降低43%和63%（p<0.05）。MK-801和U-74006F联合治疗使血管渗漏减少65%，并不显著大于单独使用任一药物预处理的效果。这些结果表明，兴奋性氨基酸和自由基均可损伤脑微血管，且兴奋性氨基酸拮抗剂可在自由基诱导的损伤后部分保护血脑屏障。
