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Differential Histopathological and Behavioral Outcomes Eight Weeks after Rat Spinal Cord Injury by Contusion, Dislocation, and Distraction Mechanisms

View Article: PubMed Central - PubMed

ABSTRACT

The objective of this study was to compare the long-term histological and behavioral outcomes after spinal cord injury (SCI) induced by one of three distinct biomechanical mechanisms: dislocation, contusion, and distraction. Thirty male Sprague-Dawley rats were randomized to incur a traumatic cervical SCI by one of these three clinically relevant mechanisms. The injured cervical spines were surgically stabilized, and motor function was assessed for the following 8 weeks. The spinal cords were then harvested for histologic analysis. Quantification of white matter sparing using Luxol fast blue staining revealed that dislocation injury caused the greatest overall loss of white matter, both laterally and along the rostrocaudal axis of the injured cord. Distraction caused enlarged extracellular spaces and structural alteration in the white matter but spared the most myelinated axons overall. Contusion caused the most severe loss of myelinated axons in the dorsal white matter. Immunohistochemistry for the neuronal marker NeuN combined with Fluoro Nissl revealed that the dislocation mechanism resulted in the greatest neuronal cell losses in both the ventral and dorsal horns. After the distraction injury mechanism, animals displayed no recovery of grip strength over time, in contrast to the animals subjected to contusion or dislocation injuries. After the dislocation injury mechanism, animals displayed no improvement in the grooming test, in contrast to the animals subjected to contusion or distraction injuries. These data indicate that different SCI mechanisms result in distinct patterns of histopathology and behavioral recovery. Understanding this heterogeneity may be important for the future development of therapeutic interventions that target specific neuropathology after SCI.

No MeSH data available.


Related in: MedlinePlus

Schematic diagrams of the anatomic damage patterns in the spinal cord. The damage to the myelinated axons in the dorsal, lateral, and ventral white matter are depicted as is the damage to the neuronal cell bodies in the gray matter. The red arrows show the directions of the mechanical deformations. The severe loss of myelinated axons after contusion can be seen in the dorsal white matter (point A). Dislocation caused the greatest overall loss of white matter tissue, especially in the lateral white matter (point B), and the rostrocaudal extent of this loss was greatest after dislocation. Dislocation also caused the greatest neuronal cell death in both the ventral and dorsal horns (point C), although the differences from contusion were small. Distraction caused substantial structural alteration in the white matter (point D), while sparing the most myelinated axons overall. Distraction also caused the most extensive lesion cavity (point E), particularly in the dorsal white matter. Neuronal survival after distraction injuries was highly variable. The schematic diagram does not accurately reflect the spinal cord areas compared with control or changes from rostral to caudal.
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f12: Schematic diagrams of the anatomic damage patterns in the spinal cord. The damage to the myelinated axons in the dorsal, lateral, and ventral white matter are depicted as is the damage to the neuronal cell bodies in the gray matter. The red arrows show the directions of the mechanical deformations. The severe loss of myelinated axons after contusion can be seen in the dorsal white matter (point A). Dislocation caused the greatest overall loss of white matter tissue, especially in the lateral white matter (point B), and the rostrocaudal extent of this loss was greatest after dislocation. Dislocation also caused the greatest neuronal cell death in both the ventral and dorsal horns (point C), although the differences from contusion were small. Distraction caused substantial structural alteration in the white matter (point D), while sparing the most myelinated axons overall. Distraction also caused the most extensive lesion cavity (point E), particularly in the dorsal white matter. Neuronal survival after distraction injuries was highly variable. The schematic diagram does not accurately reflect the spinal cord areas compared with control or changes from rostral to caudal.

Mentions: This study is the first to compare three clinically relevant mechanisms of cervical SCI up to 8 weeks post-injury in a rat model. We observed distinct differences in the histopathology across the three injury mechanisms, and a brief summary is outlined below and shown schematically in Figure 12. Contusion caused the most severe loss of myelinated axons in the dorsal white matter (point A, Fig. 12). Dislocation caused the greatest overall loss of white matter tissue, especially in the lateral white matter (point B), and the rostrocaudal extent of this loss was greatest after dislocation. Dislocation also caused the greatest neuronal cell death in both the ventral and dorsal horns (point C), although the differences from contusion were small. Distraction caused substantial structural alteration in the white matter (point D), while sparing the most myelinated axons overall. Distraction also caused the most extensive lesion cavity (point E), particularly in the dorsal white matter. These key findings highlight the complex and varied effect of different spinal cord deformations on histopathology.


Differential Histopathological and Behavioral Outcomes Eight Weeks after Rat Spinal Cord Injury by Contusion, Dislocation, and Distraction Mechanisms
Schematic diagrams of the anatomic damage patterns in the spinal cord. The damage to the myelinated axons in the dorsal, lateral, and ventral white matter are depicted as is the damage to the neuronal cell bodies in the gray matter. The red arrows show the directions of the mechanical deformations. The severe loss of myelinated axons after contusion can be seen in the dorsal white matter (point A). Dislocation caused the greatest overall loss of white matter tissue, especially in the lateral white matter (point B), and the rostrocaudal extent of this loss was greatest after dislocation. Dislocation also caused the greatest neuronal cell death in both the ventral and dorsal horns (point C), although the differences from contusion were small. Distraction caused substantial structural alteration in the white matter (point D), while sparing the most myelinated axons overall. Distraction also caused the most extensive lesion cavity (point E), particularly in the dorsal white matter. Neuronal survival after distraction injuries was highly variable. The schematic diagram does not accurately reflect the spinal cord areas compared with control or changes from rostral to caudal.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5035937&req=5

f12: Schematic diagrams of the anatomic damage patterns in the spinal cord. The damage to the myelinated axons in the dorsal, lateral, and ventral white matter are depicted as is the damage to the neuronal cell bodies in the gray matter. The red arrows show the directions of the mechanical deformations. The severe loss of myelinated axons after contusion can be seen in the dorsal white matter (point A). Dislocation caused the greatest overall loss of white matter tissue, especially in the lateral white matter (point B), and the rostrocaudal extent of this loss was greatest after dislocation. Dislocation also caused the greatest neuronal cell death in both the ventral and dorsal horns (point C), although the differences from contusion were small. Distraction caused substantial structural alteration in the white matter (point D), while sparing the most myelinated axons overall. Distraction also caused the most extensive lesion cavity (point E), particularly in the dorsal white matter. Neuronal survival after distraction injuries was highly variable. The schematic diagram does not accurately reflect the spinal cord areas compared with control or changes from rostral to caudal.
Mentions: This study is the first to compare three clinically relevant mechanisms of cervical SCI up to 8 weeks post-injury in a rat model. We observed distinct differences in the histopathology across the three injury mechanisms, and a brief summary is outlined below and shown schematically in Figure 12. Contusion caused the most severe loss of myelinated axons in the dorsal white matter (point A, Fig. 12). Dislocation caused the greatest overall loss of white matter tissue, especially in the lateral white matter (point B), and the rostrocaudal extent of this loss was greatest after dislocation. Dislocation also caused the greatest neuronal cell death in both the ventral and dorsal horns (point C), although the differences from contusion were small. Distraction caused substantial structural alteration in the white matter (point D), while sparing the most myelinated axons overall. Distraction also caused the most extensive lesion cavity (point E), particularly in the dorsal white matter. These key findings highlight the complex and varied effect of different spinal cord deformations on histopathology.

View Article: PubMed Central - PubMed

ABSTRACT

The objective of this study was to compare the long-term histological and behavioral outcomes after spinal cord injury (SCI) induced by one of three distinct biomechanical mechanisms: dislocation, contusion, and distraction. Thirty male Sprague-Dawley rats were randomized to incur a traumatic cervical SCI by one of these three clinically relevant mechanisms. The injured cervical spines were surgically stabilized, and motor function was assessed for the following 8 weeks. The spinal cords were then harvested for histologic analysis. Quantification of white matter sparing using Luxol fast blue staining revealed that dislocation injury caused the greatest overall loss of white matter, both laterally and along the rostrocaudal axis of the injured cord. Distraction caused enlarged extracellular spaces and structural alteration in the white matter but spared the most myelinated axons overall. Contusion caused the most severe loss of myelinated axons in the dorsal white matter. Immunohistochemistry for the neuronal marker NeuN combined with Fluoro Nissl revealed that the dislocation mechanism resulted in the greatest neuronal cell losses in both the ventral and dorsal horns. After the distraction injury mechanism, animals displayed no recovery of grip strength over time, in contrast to the animals subjected to contusion or dislocation injuries. After the dislocation injury mechanism, animals displayed no improvement in the grooming test, in contrast to the animals subjected to contusion or distraction injuries. These data indicate that different SCI mechanisms result in distinct patterns of histopathology and behavioral recovery. Understanding this heterogeneity may be important for the future development of therapeutic interventions that target specific neuropathology after SCI.

No MeSH data available.


Related in: MedlinePlus