PROTECTION OF THE AXONAL CYTOSKELETON IN ANOXIC OPTIC-NERVE BY DECREASED EXTRACELLULAR CALCIUM

被引:72
作者
WAXMAN, SG
BLACK, JA
RANSOM, BR
STYS, PK
机构
[1] VET ADM MED CTR,CTR NEUROSCI & REGENERAT RES,PVA EPVA,W HAVEN,CT 06516
[2] OTTAWA CIVIC HOSP,DIV NEUROL,OTTAWA K1Y 4E9,ONTARIO,CANADA
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
ANOXIA; AXON; CALCIUM-MEDIATED NEURONAL INJURY; CYTOSKELETON; MICROTUBULE; NEUROFILAMENT;
D O I
10.1016/0006-8993(93)91027-P
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Since CNS white matter tracts contain axons, oligodendrocytes and astrocytes but not synapses, it is likely that anoxic injury of white matter is mediated by cellular mechanisms that do not involve synapses. In order to test the hypothesis, that anoxic injury of white matter is mediated by an influx of Ca2+ into the intracellular compartment of axons, we compared the ultrastructure of axons in rat optic nerve exposed to 60 min of anoxia in artificial cerebrospinal fluid (aCSF) containing normal (2 mM) Ca2+, and in aCSF containing zero-Ca2+ together with 5 mM EGTA. Optic nerves fixed at the end of 60 min of anoxia in 2 mM Ca2+ exhibit extensive ultrastructural alterations including disruption of microtubules and neurofilaments within the axonal cytoskeleton, development of membranous profiles and empty spaces between the axon and the ensheathing myelin, and swelling of mitochondria with loss of cristae. Bathing the nerves in zero-Ca2+ aCSF during anoxia protected the axons from cytoskeletal changes; after 60 min of anoxia, optic nerve axons retained normal-appearing microtubules and neurofilaments. Membranous profiles were rare, and empty spaces between axons and myelin did not develop in anoxic optic nerves bathed in zero-Ca2+ aCSF. Disorganization of cristae in axonal mitochondria was observed in anoxic optic nerves even when Ca2+ was omitted from the medium. Because Ca2+-mediated injury is known to disrupt the axonal cytoskeleton, these results support the hypothesis that anoxia triggers an abnormal influx of Ca2+ into myelinated axons in CNS white matter.
引用
收藏
页码:137 / 145
页数:9
相关论文
共 33 条
[1]   ION CHANNEL ORGANIZATION OF THE MYELINATED FIBER [J].
BLACK, JA ;
KOCSIS, JD ;
WAXMAN, SG .
TRENDS IN NEUROSCIENCES, 1990, 13 (02) :48-54
[3]  
CHOI DW, 1987, J NEUROSCI, V7, P369
[4]   NERVE-FIBER CONDUCTION-VELOCITY DISTRIBUTIONS .1. ESTIMATION BASED ON THE SINGLE-FIBER AND COMPOUND ACTION POTENTIALS [J].
CUMMINS, KL ;
PERKEL, DH ;
DORFMAN, LJ .
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY, 1979, 46 (06) :634-646
[5]  
DAVIS P, 1987, Society for Neuroscience Abstracts, V13, P1634
[6]   DEVELOPMENT OF 4-AP AND TEA SENSITIVITIES IN MAMMALIAN MYELINATED NERVE-FIBERS [J].
ENG, DL ;
GORDON, TR ;
KOCSIS, JD ;
WAXMAN, SG .
JOURNAL OF NEUROPHYSIOLOGY, 1988, 60 (06) :2168-2179
[7]   NERVE FIBRES IN OPTIC NERVE OF RAT [J].
FORRESTER, J ;
PETERS, A .
NATURE, 1967, 214 (5085) :245-+
[8]  
FOSTER RE, 1982, DEV BRAIN RES, V3, P361
[9]   EXPERIMENTAL CYANIDE ENCEPHALOPATHY - ELECTRON MICROSCOPIC OBSERVATIONS OF EARLY LESIONS IN WHITE MATTER [J].
HIRANO, A ;
LEVINE, S ;
ZIMMERMAN, HM .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1967, 26 (02) :200-+
[10]  
KAMPE K, 1992, PFLUG ARCH EUR J PHY, V420, pR28