RT Journal Article
SR Electronic
T1 Effects of the Sodium Channel Blocker Tetrodotoxin on Acute White Matter Pathology After Experimental Contusive Spinal Cord Injury
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6122
OP 6133
DO 10.1523/JNEUROSCI.19-14-06122.1999
VO 19
IS 14
A1 Lisa J. Rosenberg
A1 Yang D. Teng
A1 Jean R. Wrathall
YR 1999
UL http://www.jneurosci.org/content/19/14/6122.abstract
AB 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.