Kristián T, Gidö G, Kuroda S, Schütz A, Siesjö B K
Division of Experimental Brain Research, University Hospital, Lund, Sweden.
Exp Brain Res. 1998 Jun;120(4):503-9. doi: 10.1007/s002210050424.
The present experiments were undertaken to define changes in tissue calcium metabolism in focal and perifocal ("penumbral") tissues following 2 h of transient middle cerebral artery occlusion (MCAO) in rats, induced with an intraluminal filament occlusion technique. The extracellular calcium concentration ([Ca2+]e) was measured with ion-selective microelectrodes in neocortical focus and penumbra. For measurement of total tissue calcium content, tissue samples from these areas were collected and analyzed with atomic absorption spectrometry. During MCAO, [Ca2+]e in a neocortical focal area fell from a normal value of about 1.2 mM to values around 0.1 mM, suggesting translocation of virtually all extracellular calcium to intracellular fluids. Recirculation was accompanied by re-extrusion of calcium within 5-7 min; however, [Ca2+]e never returned to normal but stabilized at about 50% of the control value for the first 6 h, and decreased further after 24 h. In penumbral areas, [Ca2+]e showed the expected transient decreases associated with spreading depression-like (or ischemic) depolarization waves. Recirculation was followed by return of [Ca2+]e towards normal values. In the focus, water content increased from about 79% to about 80.4% at the end of the 2-h period of ischemia. After 2 h and 4 h of recirculation, the edema was aggravated (mean values 81.9% and 81.2%, respectively). After 6 h and 24 h, the edema was more pronounced (83.6% and 83.8%, respectively). In the penumbra, no significant edema was observed until 6 h and 24 h of recirculation. The total tissue calcium content in the focus (expressed by unit dry weight) increased at the end of the ischemia period demonstrating calcium translocation from blood to tissue. After 6 h and 24 h, the content increased two- to threefold, compared with control. Changes in the penumbra were qualitatively similar but less pronounced, and a significant increase was not observed until after 6 h of recirculation. The results suggest that 2 h of MCAO leads to a profound perturbation of cell calcium metabolism. In focal areas, cells fail to extrude the calcium that is gradually accumulated during reperfusion and show massive calcium overload after the first 4-6 h of recirculation. Penumbral tissues show a similar increase in calcium concentration after 6 h of recirculation.
本实验旨在确定大鼠大脑中动脉短暂闭塞（MCAO）2小时后，局灶性和局灶周围（“半暗带”）组织中组织钙代谢的变化，采用腔内细丝闭塞技术诱导MCAO。用离子选择性微电极测量新皮质病灶和半暗带中的细胞外钙浓度（[Ca2+]e）。为了测量组织总钙含量，收集这些区域的组织样本并用原子吸收光谱法进行分析。在MCAO期间，新皮质病灶区域的[Ca2+]e从正常的约1.2 mM降至约0.1 mM左右的值，表明几乎所有细胞外钙都转移到了细胞内液中。再灌注伴随着钙在5 - 7分钟内的重新排出；然而，[Ca2+]e从未恢复正常，而是在最初6小时内稳定在对照值的约50%，并在24小时后进一步下降。在半暗带区域，[Ca2+]e显示出与扩散性抑制样（或缺血性）去极化波相关的预期短暂下降。再灌注后，[Ca2+]e恢复到正常值。在病灶区域，缺血2小时结束时，含水量从约79%增加到约80.4%。再灌注2小时和4小时后，水肿加重（平均值分别为81.9%和81.2%）。6小时和24小时后，水肿更明显（分别为83.6%和83.8%）。在半暗带，直到再灌注6小时和24小时才观察到明显的水肿。病灶区域的组织总钙含量（以单位干重表示）在缺血期结束时增加，表明钙从血液转移到组织中。6小时和24小时后，含量增加了两到三倍，与对照相比。半暗带的变化在性质上相似但不太明显，直到再灌注6小时后才观察到显著增加。结果表明，2小时的MCAO导致细胞钙代谢的严重紊乱。在病灶区域，细胞在再灌注期间无法排出逐渐积累的钙，并在再灌注的最初4 - 6小时后出现大量钙超载。再灌注6小时后，半暗带组织中的钙浓度也有类似的增加。
