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The dynamics of axolemmal disruption in guinea pig spinal cord following compression

  • Published:
Journal of Neurocytology

Abstract

Membrane damage has been postulated as a critical factor in mediating axonal degeneration in brain and spinal cord trauma. Despite compelling evidence of membrane disruption as a result of physical insults in both in vivo and in vitro studies, the dynamics of such damage over the time post injury in in vivo studies has not been well documented. Using a well-characterized in vivo guinea pig spinal cord compression model and horseradish peroxidase exclusion assay, we have documented significant membrane disruption at 1 hr, 3 days, and 7 days following injury. Furthermore, the membrane damage was found to spread laterally 10 mm beyond the center of original compression site in both rostral and caudal directions. A second-degree polynomial fit of the measured data predicts a bilateral spread of approximately 20–21 mm of membrane disruption from the epicenter of injury over a period of about 20 days. Thus, this study shows that membrane damage exists days, and possibly weeks, after spinal cord trauma in live guinea pigs. This provides the evidence necessary to investigate the role of membrane damage in triggering axonal deterioration in the future. Furthermore, this study has also revealed a long therapeutical window for membrane repair and functional enhancement following traumatic injury in the central nervous system.

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References

  • ASANO, T., SHI, R. & BLIGHT, A. R. (1995) Horseradish peroxidase used to examine the distribution of axonal damage in spinal cord compression injury in vitro. Journal of Neurotrauma 12, 993 (abstract).

    Google Scholar 

  • BORGENS, R. B. & SHI, R. (2000) Immediate recovery from spinal cord injury through molecular repair of nerve membranes with polyethylene glycol. FASEB Journal 14, 27-35.

    Google Scholar 

  • BORGENS, R. B., SHI, R. & BOHNERT, D. (2002) Behavioral recovery from spinal cord injury following delayed application of polyethylene glycol. Journal of Experimental Biology 205, 1-12.

    Google Scholar 

  • DUERSTOCK, B. S. & BORGENS, R. B. (2002) Three-dimentional morphometry of spinal cord injury follow polyethylene glycol treatment. Journal of Experimental Biology 205, 13-24.

    Google Scholar 

  • EMERY, D. G., LUCAS, J. H. & GROSS, G. W. (1987) The sequence of ultrastructural changes in cultured neurons after dendrite transection. Experimental Brain Research 67, 41-45.

    Google Scholar 

  • FAWCETT, J. W. & KEYNES, R. J. (1990) Peripheral nerve regeneration. Annual Review of Neuroscience 13, 43-60.

    Google Scholar 

  • FITZPATRICK, M. O., MAXWELL, W. L. & GRAHAM, D. I. (1998) The role of the axolemma in the initiation of traumatically induced axonal injury (editorial). Journal of Neurology, Neurosurgery \(\& \) Psychiatry 64, 285-287.

    Google Scholar 

  • HUANG, P. P. & YOUNG, W. (1994) The effects of arterial blood gas values on lesion volumes in a graded rat spinal cord contusion model. Journal of Neurotrauma 11, 547-562.

    Google Scholar 

  • KIM, H., KOEHLER, R. C., HURN, P. D., HALL, E. D. & TRAYSTMAN, R. J. (1996) Amelioration of impaired cerebral metabolism after severe acidotic ischemia by tririlazad postteatment in dogs. Stroke 27, 114-121.

    Google Scholar 

  • LUCAS, J. H., EMERY, D. G. & ROSENBERG, L. J. (1997) Physical injury of neurons: Important roles for sodium and chloride ions. The Neuroscientist 3, 89-101.

    Google Scholar 

  • LUCAS, J. H., GROSS, G. W., EMERY, D. G. & GARDNER, C. R. (1985) Neuronal survival or death after dendrite transection close to the perikaryon: Correlation with electrophysiologic, morphologic, and ultrastructural changes. Central Nervous System Trauma 2, 231-255.

    Google Scholar 

  • LUO, J., UCHIDA, K. & SHI, R. (2003) Lipid peroxidation products, acrolein and 4-hydroxynonenal, are increased following traumatic spinal cord injury in guinea pig (abstract). 33rd Society for Neuroscience annual meeting neurobiology of lipid sessions. Neurobiology of Lipids 2, 3.

    Google Scholar 

  • MAXWELL, W. L., DOMLEO, A., MCCOLL, G., JAFARI, S. S. & GRAHAM, D. I. (2003) Post-acute alterations in the axonal cytoskeleton after traumatic axonal injury. Journal of Neurotrauma 20, 151-168.

    Google Scholar 

  • MAXWELL, W. L., KOSANLAVIT, R., MCCREATH, B. J., REID, O. & GRAHAM, D. I. (1999) Freeze-fracture and cytochemical evidence for structural and functional alteration in the axolemma and myelin sheath of adult guinea pig optic nerve fibers after stretch injury. Journal of Neurotrauma 16, 273-284.

    Google Scholar 

  • MAXWELL, W. L., MCCREATH, B. J., GRAHAM, D. I. & GENNARELLI, T. A. (1995) Cytochemical evidence for redistribution of membrane pump calcium-ATPase and ecto-Ca-ATPase activity, and calcium influx in myelinated nerve fibers of the optic nerve after stretch injury. Journal of Neurocytology 24, 925-942.

    Google Scholar 

  • MAXWELL, W. L., WATT, C., GRAHAM, D. I. & GENNARELLI, T. A. (1993) Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates. Acta Neuropathologica 86, 136-144.

    Google Scholar 

  • MEIRI, H., SPIRA, M. E. & PARNAS, I. (1981) Membrane conductance and action potetial of a regenerating axon tip. Science 211, 709-712.

    Google Scholar 

  • PEASLEY, M. A. & SHI, R. (2002) Resistance of isolated mammalian spinal cord white matter to oxygen-glucose deprivation. American Journal of Physiology Cell Physiology 283, C980-C989.

    Google Scholar 

  • PETTUS, E. H. & POVLISHOCK, J. T. (1996) Characterization of a distinct set of intra-axonal ultrastructural changes associated with traumatically induced alteration in axolemmal permeability. Brain Research 722, 1-11.

    Google Scholar 

  • PETTUS, E. H., CHRISTMAN, C. W., GIEBEL, M. L. & POVLISHOCK, J. T. (1994) Traumatically induced altered membrane permeability: Its relationship to traumatically induced reactive axonal change. Journal of Neurotrauma 11, 507-522.

    Google Scholar 

  • POVLISHOCK, J. T. & PETTUS, E. H. (1996) Traumatically induced axonal damage: Evidence for enduring changes in axolemmal permeability with associated cytoskeletal change. Acta Neurochirurgica—Supplementum 66, 81-86.

    Google Scholar 

  • RANSOM, B. R., STYS, P. K. & WAXMAN, S. G. (1990) The pathophysiology of anoxic injury in central nervous system white matter. Stroke 21, 52-57.

    Google Scholar 

  • ROEDERER, E., GOLDBERG, N. H. & COHEN, M. J. (1983) Modification of retrograde degeneration in transected spinal axons of the lamprey by applied DC current. Journal of Neuroscience 3, 153-160.

    Google Scholar 

  • SCHWAB, M. E., KAPFHAMMER, J. P. & BANDTLOW, C. E. (1993) Inhibitors of neurite growth. Annual Review of Neuroscience 16, 565-595.

    Google Scholar 

  • SHI, R. (2002) In vivo evidence of membrane damage following compression of adult guinea pig spinal cord. Journal of Neurotrauma 19, 1394.

    Google Scholar 

  • SHI, R. & BLIGHT, A. R. (1996) Compression injury of mammalian spinal cord in vitro and the dynamics of action potential conduction failure. Journal of Neurophysiology 76, 1572-1580.

    Google Scholar 

  • SHI, R. & BORGENS, R. B. (1999) Acute repair of crushed guinea pig spinal cord by polyethylene glycol. Journal of Neurophysiology 81, 2406-2414.

    Google Scholar 

  • SHI, R. & BORGENS, R. B. (2000) Anatomic repair of nerve membrane in crushed mammalian spinal cord with Polyethylene Glycol. Journal of Neurocytology 29, 633-644.

    Google Scholar 

  • SHI, R. & PRYOR, J. D. (2000) Temperature dependence of membrane sealing following transection in mammalian spinal cord axons. Neuroscince 98, 157-166.

    Google Scholar 

  • SHI, R. & PRYOR, J. D. (2002) Pathological changes of isolated spinal cord axons in response to mechanical stretch. Neuroscience 110, 765-777.

    Google Scholar 

  • SHI, R., ASANO, T., VINING, N. C. & BLIGHT, A. R. (2000) Control of membrane sealing in injured mammalian spinal cord axons. Journal of Neurophysiology 84, 1763-1769.

    Google Scholar 

  • SHI, R., BORGENS, R. B. & BLIGHT, A. R. (1999) Functional reconnection of severed mammalian spinal cord axons with polyethylene glycol. Journal of Neurotrauma 16, 727-738.

    Google Scholar 

  • SHI, R., LUO, J. & PEASLEY, M. A. (2002) Acrolein inflicts axonal membrane disruption and conduction loss in isolated guinea pig spinal cord. Neuroscience 115, 337-340.

    Google Scholar 

  • SHI, R., LUCAS, J. H., WOLF, A. & GROSS, G. W. (1989) Calcium antagonists fail to protect mammalian spinal neurons after physical injury. Journal of Neurotrauma 6, 261-276; discussion 77-78.

    Google Scholar 

  • SHI, R., QIAO, X., EMERSON, N. & MALCOM, A. (2001) Dimethylsulfoxide enhances CNS neuronal plasma membrane resealing after injury in low temperature or low calcium. Journal of Neurocytology 30, 829-839.

    Google Scholar 

  • STOKES, B. T., FOX, P. & HOLLINDEN, G. (1983) Extracellular calcium activity in the injured spinal cord. Experimental Neurology 80, 561-572.

    Google Scholar 

  • STRAUTMAN, A. F., CORK, R. J. & ROBINSON, K. R. (1990) The distribution of free calcium in transected spinal axons and its modulation by applied electrical fields. Journal of Neuroscience 10, 3564-3575.

    Google Scholar 

  • XIE, X. & BARRETT, J. N. (1991) Membrane resealing in cultured rat septal neurons after neurite transection: Evidence for enhancement by Ca2+-triggered protease activity and cytoskeletal disassembly. Journal of Neuroscience 11, 3257-3267.

    Google Scholar 

  • YAWO, H. & KUNO, M. (1985) Calcium dependence of membrane sealing at the cut end of the cockroach giant axon. Journal of Neuroscience 5, 1626-1632.

    Google Scholar 

  • YOUNG, W. & KOREH, I. (1986) Potassium and calcium changes in injured spinal cords. Brain Research 365, 42-53.

    Google Scholar 

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Authors and Affiliations

  1. Department of Basic Medical Sciences, Institute for Applied Neurology, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana, 47907-1244, USA

    Riyi Shi

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  1. Riyi Shi
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Shi, R. The dynamics of axolemmal disruption in guinea pig spinal cord following compression. J Neurocytol 33, 203–211 (2004). https://doi.org/10.1023/B:NEUR.0000030695.76840.19

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  • DOI: https://doi.org/10.1023/B:NEUR.0000030695.76840.19

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