Katayama Y, Tamura T, Becker D P, Tsubokawa T
Division of Neurosurgery, UCLA School of Medicine 90024.
Brain Res. 1992 Apr 10;577(1):121-6. doi: 10.1016/0006-8993(92)90544-j.
This study demonstrates ischemic cellular swelling in vivo detected as changes in the concentration of 14C-sucrose pre-perfused into the extracellular space (ECS) as an ECS marker. Microdialysis was utilized as a means of perfusion and measurement of the extracellular concentration of 14C-sucrose ([14C-sucrose]e). Concomitant with an abrupt increase in [K+]e at 1-3 min following the ischemia induction, [14C-sucrose]e was also rapidly elevated. Since sucrose is not taken up by either cells or capillaries, the absolute amount of 14C-sucrose in the ECS must be unchanged. The increase therefore appears to represent a relative decrease in water volume in the ECS resulting from a movement of water into the cells, i.e. cellular swelling. Ca(2+)-free perfusate containing Co2+, which has been shown to block excitatory amino acid release during cerebral ischemia, significantly delayed the increase in [14C-sucrose]e and [K+]e. Kynurenic acid, a broad-spectrum antagonist of excitatory amino acids, administered in situ through the dialysis probe also significantly delayed the increase in [14C-sucrose]e and [K+]e. These findings indicate that the early cellular swelling occurring during cerebral ischemia is a result of massive ionic fluxes mediated by excitatory amino acids which are released by a Ca(2+)-dependent exocytotic process from the nerve terminals.
本研究证明了在体内检测到的缺血性细胞肿胀，其表现为预先灌注到细胞外间隙（ECS）作为ECS标志物的14C-蔗糖浓度的变化。微透析被用作灌注和测量细胞外14C-蔗糖浓度（[14C-蔗糖]e）的手段。在缺血诱导后1-3分钟，随着[K+]e突然增加，[14C-蔗糖]e也迅速升高。由于蔗糖既不被细胞也不被毛细血管摄取，ECS中14C-蔗糖的绝对量必须保持不变。因此，这种增加似乎代表了由于水进入细胞导致的ECS中水量的相对减少，即细胞肿胀。含Co2+的无Ca(2+)灌注液已被证明可在脑缺血期间阻断兴奋性氨基酸的释放，它显著延迟了[14C-蔗糖]e和[K+]e的增加。通过透析探针原位给予的兴奋性氨基酸的广谱拮抗剂犬尿氨酸也显著延迟了[14C-蔗糖]e和[K+]e的增加。这些发现表明，脑缺血期间早期发生的细胞肿胀是由兴奋性氨基酸介导的大量离子通量的结果，这些兴奋性氨基酸通过Ca(2+)依赖性胞吐过程从神经末梢释放。
