Imaizumi T, Kocsis J D, Waxman S G
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
J Neurotrauma. 1997 May;14(5):299-311. doi: 10.1089/neu.1997.14.299.
To examine anoxic injury in spinal cord white matter, we studied axonal conduction in the dorsal columns during and following a standard 60 min anoxic insult at 36 degrees C. Perfusion of the spinal cord in 0-Ca2+ Ringer solution resulted in significantly improved recovery of the compound action potential. Similarly, removal of Na+ from the perfusate resulted in significantly improved recovery of conduction in dorsal column axons. Exposure of the anoxic spinal cord to the Na+ channel blocker tetrodotoxin (TTX), the Na-Ca exchange blockers benzamil and bepridil, Na(+)-H+ exchange blockers amiloride and harmaline, and perfusion in Ringer solution with pH adjusted to 6.4, all resulted in improved recovery. The tertiary anesthetics procaine and lidocaine, as well as phenytoin and carbamazepine, also resulted in improved recovery of compound action potential amplitude after 60 min of anoxia. These results demonstrate that a significant component of irreversible loss of conduction, following anoxic injury of the dorsal columns, is Ca(2+)-dependent. Moreover, these results demonstrate that TTX-inhibitable Na+ channels participate in the pathophysiology of anoxic injury in spinal cord white matter, and indicate that reverse Na-Ca exchange provides a route for at least part of the damaging influx of Ca2+ into an intracellular compartment in anoxic spinal cord white matter. Our results also suggest that extracellular acidosis may have a protective effect on anoxic spinal cord white matter, and support the hypothesis that anoxic injury of spinal cord white matter may involve the Na(+)-H+ exchanger.
为了研究脊髓白质中的缺氧损伤，我们在36℃下进行标准的60分钟缺氧损伤期间及之后，研究了背柱中的轴突传导。在0-Ca2+林格液中灌注脊髓可显著改善复合动作电位的恢复。同样，从灌注液中去除Na+可显著改善背柱轴突传导的恢复。将缺氧的脊髓暴露于Na+通道阻滞剂河豚毒素（TTX）、Na-Ca交换阻滞剂苄胺和苄普地尔、Na(+)-H+交换阻滞剂阿米洛利和哈马灵，并在pH值调至6.4的林格液中灌注，均导致恢复改善。叔麻醉药普鲁卡因和利多卡因，以及苯妥英和卡马西平，在缺氧60分钟后也导致复合动作电位幅度的恢复改善。这些结果表明，背柱缺氧损伤后传导不可逆丧失的一个重要组成部分是Ca(2+)依赖性的。此外，这些结果表明TTX可抑制的Na+通道参与脊髓白质缺氧损伤的病理生理学，并表明反向Na-Ca交换为缺氧脊髓白质中至少部分Ca2+流入细胞内室的损伤性内流提供了一条途径。我们的结果还表明细胞外酸中毒可能对缺氧脊髓白质有保护作用，并支持脊髓白质缺氧损伤可能涉及Na(+)-H+交换体的假说。
