 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
Volume 17, Number 11, Issue of June 1, 1997 pp. 4359-4366
Copyright ©1997 Society for NeuroscienceLocal Blockade of Sodium Channels by Tetrodotoxin Ameliorates Tissue Loss and Long-Term Functional Deficits Resulting from Experimental Spinal Cord Injury
Received Jan. 21, 1997; revised March 20, 1997; accepted March 25, 1997.
Yang Dong Teng and Jean R. Wrathall Department of Cell Biology, Neurobiology Division, Georgetown University, Washington, D.C. 20007
Although relatively little is known of the mechanisms involved in secondary axonal loss after spinal cord injury (SCI), recent data from in vitro models of white matter (WM) injury have implicated abnormal sodium influx as a key event. We hypothesized that blockade of sodium channels after SCI would reduce WM loss and long-term functional deficits. To test this hypothesis, a sufficient and safe dose (0.15 nmol) of the potent Na+ channel blocker tetrodotoxin (TTX) was determined through a dose-response study. We microinjected TTX or vehicle (VEH) into the injury site at 15 min after a standardized contusive SCI in the rat. Behavioral tests were performed 1 d after injury and weekly thereafter. Quantitative histopathology at 8 weeks postinjury showed that TTX treatment significantly reduced tissue loss at the injury site, with greater effect on sparing of WM than gray matter. TTX did not change the pattern of chronic histopathology typical of this SCI model, but restricted its extent, tripled the area of residual WM at the epicenter, and reduced the average length of the lesions. Serotonin immunoreactivity caudal to the epicenter, a marker for descending motor control axons, was nearly threefold that of VEH controls. The increase in WM at the epicenter was significantly correlated with the decrease in functional deficits. The TTX group exhibited a significantly enhanced recovery of coordinated hindlimb functions, more normal hindlimb reflexes, and earlier establishment of a reflex bladder. The results demonstrate that Na+ channels play a critical role in WM loss in vivo after SCI.
Key words: rat; spinal cord injury; sodium channel; tetrodotoxin; white matter injury; motor function; histopathology
This article has been cited by other articles:
J. A. Wang, W. Lin, T. Morris, U. Banderali, P. F. Juranka, and C. E. Morris
Membrane trauma and Na+ leak from Nav1.6 channels
Am J Physiol Cell Physiol, October 1, 2009; 297(4): C823 - C834.
[Abstract] [Full Text] [PDF]
J. A. Black, S. Liu, B. C. Hains, C. Y. Saab, and S. G. Waxman
Long-term protection of central axons with phenytoin in monophasic and chronic-relapsing EAE
Brain, December 1, 2006; 129(12): 3196 - 3208.
[Abstract] [Full Text] [PDF]
M. Ouardouz, S. Malek, E. Coderre, and P. K. Stys
Complex interplay between glutamate receptors and intracellular Ca2+ stores during ischaemia in rat spinal cord white matter
J. Physiol., November 15, 2006; 577(1): 191 - 204.
[Abstract] [Full Text] [PDF]
J.-Y. C. Hsu, R. McKeon, S. Goussev, Z. Werb, J.-U. Lee, A. Trivedi, and L. J. Noble-Haeusslein
Matrix Metalloproteinase-2 Facilitates Wound Healing Events That Promote Functional Recovery after Spinal Cord Injury
J. Neurosci., September 27, 2006; 26(39): 9841 - 9850.
[Abstract] [Full Text] [PDF]
H. Choi, W.-L. Liao, K. M. Newton, R. C. Onario, A. M. King, F. C. Desilets, E. J. Woodard, M. E. Eichler, W. R. Frontera, S. Sabharwal, et al.
Respiratory Abnormalities Resulting from Midcervical Spinal Cord Injury and their Reversal by Serotonin 1A Agonists in Conscious Rats
J. Neurosci., May 4, 2005; 25(18): 4550 - 4559.
[Abstract] [Full Text] [PDF]
A. Iwata, P. K. Stys, J. A. Wolf, X.-H. Chen, A. G. Taylor, D. F. Meaney, and D. H. Smith
Traumatic Axonal Injury Induces Proteolytic Cleavage of the Voltage-Gated Sodium Channels Modulated by Tetrodotoxin and Protease Inhibitors
J. Neurosci., May 12, 2004; 24(19): 4605 - 4613.
[Abstract] [Full Text] [PDF]
Y. D. Teng, H. Choi, R. C. Onario, S. Zhu, F. C. Desilets, S. Lan, E. J. Woodard, E. Y. Snyder, M. E. Eichler, and R. M. Friedlander
Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury
PNAS, March 2, 2004; 101(9): 3071 - 3076.
[Abstract] [Full Text] [PDF]
A. C. Lo, C. Y. Saab, J. A. Black, and S. G. Waxman
Phenytoin Protects Spinal Cord Axons and Preserves Axonal Conduction and Neurological Function in a Model of Neuroinflammation In Vivo
J Neurophysiol, November 1, 2003; 90(5): 3566 - 3571.
[Abstract] [Full Text] [PDF]
S. A. Malek, E. Coderre, and P. K. Stys
Aberrant Chloride Transport Contributes to Anoxic/Ischemic White Matter Injury
J. Neurosci., May 1, 2003; 23(9): 3826 - 3836.
[Abstract] [Full Text] [PDF]
I. M. Medana and M. M. Esiri
Axonal damage: a key predictor of outcome in human CNS diseases
Brain, March 1, 2003; 126(3): 515 - 530.
[Abstract] [Full Text] [PDF]
J. A. Wolf, P. K. Stys, T. Lusardi, D. Meaney, and D. H. Smith
Traumatic Axonal Injury Induces Calcium Influx Modulated by Tetrodotoxin-Sensitive Sodium Channels
J. Neurosci., March 15, 2001; 21(6): 1923 - 1930.
[Abstract] [Full Text] [PDF]
V. Pikov and J. R. Wrathall
Coordination of the Bladder Detrusor and the External Urethral Sphincter in a Rat Model of Spinal Cord Injury: Effect of Injury Severity
J. Neurosci., January 15, 2001; 21(2): 559 - 569.
[Abstract] [Full Text] [PDF]
S. Li and P. K. Stys
Mechanisms of Ionotropic Glutamate Receptor-Mediated Excitotoxicity in Isolated Spinal Cord White Matter
J. Neurosci., February 1, 2000; 20(3): 1190 - 1198.
[Abstract] [Full Text] [PDF]
R. M. LoPachin, C. L. Gaughan, E. J. Lehning, Y. Kaneko, T. M. Kelly, and A. Blight
Experimental Spinal Cord Injury: Spatiotemporal Characterization of Elemental Concentrations and Water Contents in Axons and Neuroglia
J Neurophysiol, November 1, 1999; 82(5): 2143 - 2153.
[Abstract] [Full Text] [PDF]
Y. D. Teng, I. Mocchetti, A. M. Taveira-DaSilva, R. A. Gillis, and J. R. Wrathall
Basic Fibroblast Growth Factor Increases Long-Term Survival of Spinal Motor Neurons and Improves Respiratory Function after Experimental Spinal Cord Injury
J. Neurosci., August 15, 1999; 19(16): 7037 - 7047.
[Abstract] [Full Text] [PDF]
S. D. Grossman, B. B. Wolfe, R. P. Yasuda, and J. R. Wrathall
Alterations in AMPA Receptor Subunit Expression after Experimental Spinal Cord Contusion Injury
J. Neurosci., July 15, 1999; 19(14): 5711 - 5720.
[Abstract] [Full Text] [PDF]
L. J. Rosenberg, Y. D. Teng, and J. R. Wrathall
Effects of the Sodium Channel Blocker Tetrodotoxin on Acute White Matter Pathology After Experimental Contusive Spinal Cord Injury
J. Neurosci., July 15, 1999; 19(14): 6122 - 6133.
[Abstract] [Full Text] [PDF]
L. J. Rosenberg, Y. D. Teng, and J. R. Wrathall
2,3-Dihydroxy-6-Nitro-7-Sulfamoyl-Benzo(f)Quinoxaline Reduces Glial Loss and Acute White Matter Pathology after Experimental Spinal Cord Contusion
J. Neurosci., January 1, 1999; 19(1): 464 - 475.
[Abstract] [Full Text] [PDF]
J. R. Wrathall, W. Li, and L. D. Hudson
Myelin Gene Expression after Experimental Contusive Spinal Cord Injury
J. Neurosci., November 1, 1998; 18(21): 8780 - 8793.
[Abstract] [Full Text] [PDF]
S. Li, G. A. R. Mealing, P. Morley, and P. K. Stys
Novel Injury Mechanism in Anoxia and Trauma of Spinal Cord White Matter: Glutamate Release via Reverse Na+-dependent Glutamate Transport
J. Neurosci., July 15, 1999; 19(14): RC16 - RC16.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|