Lucas J H, Emery D G, Higgins M L, Gross G W
Department of Biological Sciences, University of North Texas, Denton.
J Neurotrauma. 1990 Fall;7(3):169-92. doi: 10.1089/neu.1990.7.169.
To determine the contributions of calcium to development of ultrastructural damage and neuronal death after mechanical injury, we amputated primary dendrites from over 300 cultured mammalian spinal neurons under normal (1.8 mM) or low (less than or equal to 30 microM) calcium conditions. Two general categories of early ultrastructural change were seen in both normal and low calcium: (1) a lesion-dependent gradient of damage that moved centripetally through the proximal segment and penetrated the soma within 15 min and (2) dilation of the somal Golgi/smooth endoplasmic reticulum (SER), which preceded the wave of deterioration from the lesion. Although the somal Golgi/SER changes were similar in both normal and low calcium, the damage gradient in low calcium differed from the damage gradient in normal calcium. (1) Microtubules and neurofilaments were preserved, (2) mitochondria became more electron dense but did not develop electronlucent foci or high amplitude swelling, and (3) an extensive vesicular gradient formed consisting of rows of swollen SER vesicles. Sodium ionophores have been reported to cause similar changes. Survival studies showed that calcium reduction significantly delayed neuronal death. Survival was 63 +/- 16% vs 35 +/- 8% (p less than 0.003) at 2 h and 30 +/- 7% vs 23 +/- 8% at 6 h in low and normal calcium, respectively. Dead neurons that had been lesioned in low calcium also showed greater ultrastructural preservation than neurons that died after dendrotomy in normal calcium. We hypothesize that under low calcium conditions, the large sodium injury current plays an important role in neuronal deterioration and death after mechanical trauma.
为了确定钙在机械损伤后超微结构损伤和神经元死亡发展过程中的作用，我们在正常（1.8 mM）或低钙（小于或等于30 microM）条件下，从300多个培养的哺乳动物脊髓神经元上切断初级树突。在正常钙和低钙条件下均观察到两种早期超微结构变化：（1）损伤依赖性损伤梯度，其向心穿过近端节段并在15分钟内穿透胞体；（2）胞体高尔基体/滑面内质网（SER）扩张，这在损伤导致的恶化波之前出现。尽管正常钙和低钙条件下胞体高尔基体/SER的变化相似，但低钙条件下的损伤梯度与正常钙条件下的损伤梯度不同。（1）微管和神经丝得以保留；（2）线粒体电子密度增加，但未出现电子透亮灶或高幅度肿胀；（3）形成了由一排排肿胀的SER囊泡组成的广泛囊泡梯度。据报道，钠离子载体可引起类似变化。存活研究表明，降低钙浓度可显著延迟神经元死亡。在低钙和正常钙条件下，2小时时的存活率分别为63±16%和35±8%（p<0.003），6小时时分别为30±7%和23±8%。在低钙条件下受损的死亡神经元，其超微结构保存也比在正常钙条件下树突切断后死亡的神经元更好。我们推测，在低钙条件下，大量的钠损伤电流在机械创伤后神经元的恶化和死亡中起重要作用。
