Endogenous recovery of injured spinal cord: Longitudinal in vivo magnetic resonance imaging

Pathological changes were followed longitudinally with in vivo magnetic resonance imaging (MRI) and behavioral studies in experimental spinal cord injury (SCI). MRI‐observed pathology was correlated with histology. On MRI, the cavitated regions of the injured cord were gradually filled with viable tissue between two and 8 weeks postinjury, and a concomitant improvement was observed in the neurobehavioral scores. By weeks 3–6, on MRI, the gray matter (GM) returned in the segments caudal, but not rostral, to the injury site. The corresponding histological sections revealed motor neurons as well as other nuclei in the gray matter immediately caudal to the epicenter, but not at the site of injury, suggesting neuronal recovery in perilesioned areas. The neuronal and neurological recovery appeared to occur about the same time as neovasculature that was reported on the contrast‐enhanced MRI, suggesting a role for angiogenesis in recovery from SCI. The role of angiogenesis in neuronal recovery is further supported by the immunohistochemical observation of greater bromodeoxyuridine uptake by blood vessels near the lesion site compared with uninjured cords. © 2004 Wiley‐Liss, Inc.

[1]  L. Guth,et al.  Experimental Spinal Cord Injury: Wallerian Degeneration in the Dorsal Column Is Followed by Revascularization, Glial Proliferation, and Nerve Regeneration , 1997, Experimental Neurology.

[2]  R. Pallini,et al.  Promotion of regeneration of corticospinal tract axons in rats with recombinant vascular endothelial growth factor alone and combined with adenovirus coding for this factor. , 2002, Journal of neurosurgery.

[3]  M. Tuszynski,et al.  Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[4]  P. Narayana,et al.  Characterization of an Experimental Spinal Cord Injury Model Using Waveform and Morphometric Analysis , 1996, Spine.

[5]  J. Hedges,et al.  Inability to validate a predictive score for infective endocarditis in intravenous drug users. , 1993, The Journal of emergency medicine.

[6]  Charles Tator.  Biology of neurological recovery and functional restoration after spinal cord injury. , 1998, Neurosurgery.

[7]  P. London.  Injury , 1969, Definitions.

[8]  P. Quesenberry,et al.  Studies on BrdU labeling of hematopoietic cells: Stem cells and cell lines , 2003, Journal of cellular physiology.

[9]  M. Bilgen,et al.  Dynamic contrast‐enhanced MRI of experimental spinal cord injury: In vivo serial studies , 2001, Magnetic resonance in medicine.

[10]  M. Schwab,et al.  Local Changes in Vascular Architecture Following Partial Spinal Cord Lesion in the Rat , 1997, Experimental Neurology.

[11]  M. Bilgen,et al.  In vivo assessment of blood-spinal cord barrier permeability: serial dynamic contrast enhanced MRI of spinal cord injury. , 2002, Magnetic resonance imaging.

[12]  B. Stokes,et al.  A Quantitative Spatial Analysis of the Blood–Spinal Cord Barrier I. Permeability Changes after Experimental Spinal Contusion Injury , 1996, Experimental Neurology.

[13]  R. Bunge,et al.  The changes in human spinal sympathetic preganglionic neurons after spinal cord injury , 1999, Spinal Cord.

[14]  D. Johnston,et al.  Does loss of gray‐ and white‐matter contrast in injured spinal cord signify secondary injury? In vivo longitudinal MRI studies , 1999, Magnetic resonance in medicine.

[15]  Martin E Schwab,et al.  The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats , 2004, Nature Neuroscience.

[16]  M. Beattie,et al.  A behavioral and anatomical analysis of spinal cord injury produced by a feedback-controlled impaction device , 1987, Experimental Neurology.

[17]  G. Savić,et al.  Long-term survival in spinal cord injury: a fifty year investigation , 1998, Spinal Cord.

[18]  M. Bilgen,et al.  Spatial and temporal evolution of hemorrhage in the hyperacute phase of experimental spinal cord injury: In vivo magnetic resonance imaging , 2000, Magnetic resonance in medicine.

[19]  I. Elshafiey,et al.  In vivo magnetic resonance microscopy of rat spinal cord at 7 T using implantable RF coils , 2001, Magnetic resonance in medicine.

[20]  D. Basso,et al.  A sensitive and reliable locomotor rating scale for open field testing in rats. , 1995, Journal of neurotrauma.

[21]  W. Collins,et al.  Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study. , 1992, Journal of neurosurgery.

[22]  P. Wood,et al.  New Vascular Tissue Rapidly Replaces Neural Parenchyma and Vessels Destroyed by a Contusion Injury to the Rat Spinal Cord , 2002, Experimental Neurology.

[23]  M. Norenberg,et al.  Schwannosis: role of gliosis and proteoglycan in human spinal cord injury. , 2000, Journal of neurotrauma.

[24]  L. Noble,et al.  Vascular events after spinal cord injury: contribution to secondary pathogenesis. , 2000, Physical therapy.

[25]  M. Sparkes.  Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data , 1992 .

[26]  J. A. Gruner,et al.  Histological and functional evaluation of experimental spinal cord injury: evidence of a stepwise response to graded compression , 1996, Brain Research.

[27]  P I Terasaki,et al.  Long-term survival. , 1988, Clinical transplants.

[28]  W. Young,et al.  Secondary injury mechanisms in acute spinal cord injury. , 1993, The Journal of emergency medicine.

[29]  C. Hulsebosch,et al.  Direct evidence of primary afferent sprouting in distant segments following spinal cord injury in the rat: colocalization of GAP-43 and CGRP , 2003, Experimental Neurology.

[30]  W. Young,et al.  Endogenous Repair after Spinal Cord Contusion Injuries in the Rat , 1997, Experimental Neurology.

[31]  D. Burke,et al.  Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat , 2002, The Journal of comparative neurology.

[32]  M. Tuszynski,et al.  Spontaneous and augmented growth of axons in the primate spinal cord: Effects of local injury and nerve growth factor‐secreting cell grafts , 2002, The Journal of comparative neurology.

[33]  Lars Olson,et al.  High-Resolution MRI of Intact and Transected Rat Spinal Cord , 1998, Experimental Neurology.

[34]  A. Blight.  Remyelination, revascularization, and recovery of function in experimental spinal cord injury. , 1993, Advances in neurology.

[35]  P. Narayana,et al.  Quantitative MRI of spinal cord injury in a rat model , 1994, Magnetic resonance in medicine.

[36]  L. Olson,et al.  Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury , 2003, Neuroscience.

[37]  O. Steward,et al.  Ascending sensory, but not other long‐tract axons, regenerate into the connective tissue matrix that forms at the site of a spinal cord injury in mice , 2003, The Journal of comparative neurology.

[38]  Martin E. Schwab,et al.  Plasticity of motor systems after incomplete spinal cord injury , 2001, Nature Reviews Neuroscience.

[39]  D. Tracey.  Ascending and descending pathways in the spinal cord , 2004 .