Temporal–Spatial Pattern of Acute Neuronal and Glial Loss after Spinal Cord Contusion

The secondary loss of neurons and glia over the first 24 h after spinal cord injury (SCI) contributes to the permanent functional deficits that are the unfortunate consequence of SCI. The progression of this acute secondary cell death in specific neuronal and glial populations has not previously been investigated in a quantitative manner. We used a well-characterized model of SCI to analyze the loss of ventral motoneurons (VMN) and ventral funicular astrocytes and oligodendrocytes at 15 min and 4, 8, and 24 h after an incomplete midthoracic contusion injury in the rat. We found that both the length of lesion and the length of spinal cord devoid of VMN increased in a time-dependent manner. The extent of VMN loss at specified distances rostral and caudal to the injury epicenter progressed symmetrically with time. Neuronal loss was accompanied by a loss of glial cells in ventral white matter that was significant at the epicenter by 4 h after injury. Oligodendrocyte loss followed the same temporal pattern as that of VMN while astrocyte loss was delayed. This information on the temporal-spatial pattern of cell loss can be used to investigate mechanisms involved in secondary injury of neurons and glia after SCI.

[1]  J. Wrathall,et al.  Relationship of Altered Glutamate Receptor Subunit mRNA Expression to Acute Cell Loss after Spinal Cord Contusion , 2001, Experimental Neurology.

[2]  J. Wrathall,et al.  Changes in NMDA Receptor Subunit Expression in Response to Contusive Spinal Cord Injury , 2000, Journal of neurochemistry.

[3]  G. L. Li,et al.  Apoptosis of oligodendrocytes occurs for long distances away from the primary injury after compression trauma to rat spinal cord , 1999, Acta Neuropathologica.

[4]  T. Yamamoto,et al.  Apoptotic cells associated with Wallerian degeneration after experimental spinal cord injury: a possible mechanism of oligodendroglial death. , 1999, Journal of neurotrauma.

[5]  M. Mattson,et al.  Basic fibroblast growth factor (bFGF) enhances tissue sparing and functional recovery following moderate spinal cord injury. , 1999, Journal of neurotrauma.

[6]  J. Wrathall,et al.  Basic Fibroblast Growth Factor Increases Long-Term Survival of Spinal Motor Neurons and Improves Respiratory Function after Experimental Spinal Cord Injury , 1999, The Journal of Neuroscience.

[7]  P. Knapp,et al.  Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury , 1999, Nature Medicine.

[8]  J. Wrathall,et al.  Effects of the Sodium Channel Blocker Tetrodotoxin on Acute White Matter Pathology After Experimental Contusive Spinal Cord Injury , 1999, The Journal of Neuroscience.

[9]  T. Sakou,et al.  Apoptosis following spinal cord injury in rats and preventative effect of N-methyl-D-aspartate receptor antagonist. , 1999, Journal of neurosurgery.

[10]  B. Pike,et al.  Temporal Profile of Apoptotic-like Changes in Neurons and Astrocytes Following Controlled Cortical Impact Injury in the Rat , 1999, Experimental Neurology.

[11]  J. Wrathall,et al.  2,3-Dihydroxy-6-Nitro-7-Sulfamoyl-Benzo(f)Quinoxaline Reduces Glial Loss and Acute White Matter Pathology after Experimental Spinal Cord Contusion , 1999, The Journal of Neuroscience.

[12]  J. E. Vaughn,et al.  Differential vulnerability of autonomic and somatic motor neurons to N-methyl- d-aspartate-induced excitotoxicity , 1998, Neuroscience.

[13]  L. Lenke,et al.  Apoptosis as a mechanism of neuronal cell death following acute experimental spinal cord injury , 1998, Spinal Cord.

[14]  K. Abe,et al.  Delayed and selective motor neuron death after transient spinal cord ischemia: a role of apoptosis? , 1998, The Journal of thoracic and cardiovascular surgery.

[15]  M. Beattie,et al.  Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats , 1997, Journal of neuroscience research.

[16]  M. Jacquin,et al.  Neuronal Apoptosis and Necrosis Following Spinal Cord Ischemia in the Rat , 1997, Experimental Neurology.

[17]  J. Wrathall,et al.  Quantitative analysis of acute axonal pathology in experimental spinal cord contusion. , 1997, Journal of neurotrauma.

[18]  M. Jacquin,et al.  Neuronal and Glial Apoptosis after Traumatic Spinal Cord Injury , 1997, The Journal of Neuroscience.

[19]  J. Wrathall,et al.  Local Blockade of Sodium Channels by Tetrodotoxin Ameliorates Tissue Loss and Long-Term Functional Deficits Resulting from Experimental Spinal Cord Injury , 1997, The Journal of Neuroscience.

[20]  M. Jacquin,et al.  Slowly triggered excitotoxicity occurs by necrosis in cortical cultures , 1997, Neuroscience.

[21]  J. Bresnahan,et al.  Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys , 1997, Nature Medicine.

[22]  J. E. Vaughn,et al.  Differential Vulnerability of Two Subsets of Spinal Motor Neurons in Amyotrophic Lateral Sclerosis , 1996, Experimental Neurology.

[23]  K. Katoh,et al.  Induction and its spread of apoptosis in rat spinal cord after mechanical trauma , 1996, Neuroscience Letters.

[24]  K. Kinzler,et al.  Expression of the APC tumor suppressor protein in oligodendroglia , 1996, Glia.

[25]  Michael S. Beattie,et al.  Graded Histological and Locomotor Outcomes after Spinal Cord Contusion Using the NYU Weight-Drop Device versus Transection , 1996, Experimental Neurology.

[26]  G. L. Li,et al.  Apoptosis and Expression of Bcl‐2 after Compression Trauma to Rat Spinal Cord , 1996, Journal of neuropathology and experimental neurology.

[27]  R. Coggeshall,et al.  Methods for determining numbers of cells and synapses: A case for more uniform standards of review , 1996, The Journal of comparative neurology.

[28]  S. Lipton,et al.  Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Wrathall,et al.  Dose-dependent reduction of tissue loss and functional impairment after spinal cord trauma with the AMPA/kainate antagonist NBQX , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  M. Mizuguchi,et al.  Expression of Bcl-2 protein in murine neural cells in culture , 1994, Brain Research.

[31]  W. Young,et al.  Elevation and Clearance of Extracellular K+ Following Graded Contusion of the Rat Spinal Cord , 1994, Experimental Neurology.

[32]  Y. Ben‐Ari,et al.  Glutamate‐Induced Neuronal Death Is Not a Programmed Cell Death in Cerebellar Culture , 1993, Journal of neurochemistry.

[33]  D. Choi Excitotoxic cell death. , 1992, Journal of neurobiology.

[34]  B. Stokes,et al.  Three-dimensional computer-assisted analysis of graded contusion lesions in the spinal cord of the rat. , 1991, Journal of neurotrauma.

[35]  L. Noble,et al.  Correlative analyses of lesion development and functional status after graded spinal cord contusive injuries in the rat , 1989, Experimental Neurology.

[36]  M. Panjabi,et al.  Biomechanical Analysis of Experimental Spinal Cord Injury and Functional Loss , 1988, Spine.

[37]  J. Wrathall,et al.  Spinal cord contusion in the rat: somatosensory evoked potentials as a function of graded injury. , 1988, Journal of neurotrauma.

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

[39]  J. Wrathall,et al.  Spinal cord contusion in the rat: Production of graded, reproducible, injury groups , 1985, Experimental Neurology.

[40]  L. Noble,et al.  Spinal cord contusion in the rat: Morphometric analyses of alterations in the spinal cord , 1985, Experimental Neurology.

[41]  Karen Gale,et al.  Spinal cord contusion in the rat: Behavioral analysis of functional neurologic impairment , 1985, Experimental Neurology.