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The Journal of Neuroscience, July 15, 1999, 19(14):6122-6133
Effects of the Sodium Channel Blocker Tetrodotoxin on Acute White
Matter Pathology After Experimental Contusive Spinal Cord
Injury
Lisa J.
Rosenberg,
Yang D.
Teng, and
Jean R.
Wrathall
Neurobiology Division, Department of Cell Biology, Georgetown
University, Washington, DC 20007
Focal microinjection of tetrodotoxin (TTX), a potent voltage-gated
sodium channel blocker, reduces neurological deficits and tissue loss
after spinal cord injury (SCI). Significant sparing of white matter
(WM) is seen at 8 weeks after injury and is correlated to a reduction
in functional deficits. To determine whether TTX exerts an acute effect
on WM pathology, Sprague Dawley rats were subjected to a standardized
weight-drop contusion at T8 (10 gm × 2.5 cm). TTX (0.15 nmol) or
vehicle solution was injected into the injury site 5 or 15 min later.
At 4 and 24 hr, ventromedial WM from the injury epicenter was compared
by light and electron microscopy and immunohistochemistry. By 4 hr
after SCI, axonal counts revealed reduced numbers of axons and
significant loss of large ( 5 µm)-diameter axons. TTX treatment
significantly reduced the loss of large-diameter axons. In addition,
TTX significantly attenuated axoplasmic pathology at both 4 and 24 hr
after injury. In particular, the development of extensive periaxonal
spaces in the large-diameter axons was reduced with TTX treatment. In contrast, there was no significant effect of TTX on the loss of WM glia
after SCI. Thus, the long-term effects of TTX in reducing WM loss after
spinal cord injury appear to be caused by the reduction of acute axonal
pathology. These results support the hypothesis that TTX-sensitive
sodium channels at axonal nodes of Ranvier play a significant role in
the secondary injury of WM after SCI.
Key words:
spinal cord injury; TTX; electron microscopy; white
matter; glia; microinjection
Copyright © 1999 Society for Neuroscience 0270-6474/99/19146122-12$05.00/0
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