Waxman S G, Black J A, Ransom B R, Stys P K
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.
Brain Res. 1994 May 2;644(2):197-204. doi: 10.1016/0006-8993(94)91680-2.
Physiological studies in the anoxic rat optic nerve indicate that irreversible loss of function, measured by the compound action potential, is due to depolarization and run-down of the transmembrane Na+ gradient which triggers Ca2+ entry through reverse Na(+)-Ca2+ exchange. EM studies in the anoxic optic nerve have demonstrated characteristic changes, including mitochondrial swelling and dissolution of cristae, submyelinic vacuoles, detachment of perinodal oligodendrocyte-axon loops, and severe cytoskeletal damage with loss of microtubules and neurofilaments within the axoplasm. To further examine the coupling between Na+ influx and Ca(2+)-mediated injury in myelinated axons within anoxic white matter, we have examined the ultrastructural effects of tetrodotoxin (TTX), in the anoxic optic nerve. Optic nerves, maintained in an interface brain slice chamber, were exposed to a 60-min period of anoxia. TTX (1 microM) was introduced 10 min before the onset of anoxia. Nerves were examined at the end of the anoxic period, or after 80 min in 1 microM TTX for normoxic controls. Under normoxic conditions, optic nerve axons exposed to TTX exhibited a normal ultrastructure. In optic nerves exposed to TTX studied at the end of a 60-min period of anoxia, mitochondria showed swelling and loss of cristae, and terminal oligodendroglial loops were detached from the nodal axon membrane. Cytoskeletal architecture was preserved in anoxic optic nerve axons treated with TTX, and axonal microtubules and neurofilaments maintained their continuity. Submyelinic empty spaces were not present. Perinodal astrocyte processes often appeared to be replaced by cellular remnants containing multiple membranous profiles; clusters of shrunken astrocytic processes were present between myelinated axons.(ABSTRACT TRUNCATED AT 250 WORDS)
对缺氧大鼠视神经的生理学研究表明，通过复合动作电位测量的不可逆功能丧失是由于跨膜Na⁺梯度的去极化和降低，这会触发Ca²⁺通过反向Na⁺-Ca²⁺交换进入。对缺氧视神经的电子显微镜研究已经证明了特征性变化，包括线粒体肿胀和嵴溶解、髓鞘下空泡、结周少突胶质细胞-轴突环分离，以及轴浆内微管和神经丝丧失导致的严重细胞骨架损伤。为了进一步研究缺氧白质中有髓轴突中Na⁺内流与Ca²⁺介导的损伤之间的耦合关系，我们研究了缺氧视神经中河豚毒素（TTX）的超微结构效应。将置于界面脑片室中的视神经暴露于60分钟的缺氧环境。在缺氧开始前10分钟引入TTX（1微摩尔）。在缺氧期结束时检查神经，或在1微摩尔TTX中处理80分钟后作为常氧对照进行检查。在常氧条件下，暴露于TTX的视神经轴突表现出正常的超微结构。在60分钟缺氧期结束时研究的暴露于TTX的视神经中，线粒体显示肿胀和嵴丧失，终末少突胶质环从结轴突膜分离。用TTX处理的缺氧视神经轴突中的细胞骨架结构得以保留，轴突微管和神经丝保持其连续性。不存在髓鞘下空隙。结周星形胶质细胞突起常似乎被含有多个膜性结构的细胞残余物取代；在有髓轴突之间存在收缩的星形胶质细胞突起簇。（摘要截断于250字）
