Sg. Waxman et al., PROTECTION OF THE AXONAL CYTOSKELETON IN ANOXIC OPTIC-NERVE BY DECREASED EXTRACELLULAR CALCIUM, Brain research, 614(1-2), 1993, pp. 137-145
Since CNS white matter tracts contain axons, oligodendrocytes and astr
ocytes but not synapses, it is likely that anoxic injury of white matt
er is mediated by cellular mechanisms that do not involve synapses. In
order to test the hypothesis, that anoxic injury of white matter is m
ediated by an influx of Ca2+ into the intracellular compartment of axo
ns, we compared the ultrastructure of axons in rat optic nerve exposed
to 60 min of anoxia in artificial cerebrospinal fluid (aCSF) containi
ng 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 C
a2+ exhibit extensive ultrastructural alterations including disruption
of microtubules and neurofilaments within the axonal cytoskeleton, de
velopment of membranous profiles and empty spaces between the axon and
the ensheathing myelin, and swelling of mitochondria with loss of cri
stae. 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. Membr
anous profiles were rare, and empty spaces between axons and myelin di
d not develop in anoxic optic nerves bathed in zero-Ca2+ aCSF. Disorga
nization of cristae in axonal mitochondria was observed in anoxic opti
c nerves even when Ca2+ was omitted from the medium. Because Ca2+-medi
ated 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.