Limits...
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 three spinal cord injury (SCI) mechanisms. The spinal column orientation for (a) the normal animal and (b–d) the three SCI mechanisms is shown. To produce contusion injury, external displacement was applied to the dorsal spinal cord between C5 and C6 by an actuator with a 2-mm–diameter tip after laminectomy. To produce dislocation injury, external displacement was applied to the transverse processes at C6 and C7 dorsal to C5 by the actuator with vertebral clamps after facetectomy. To produce distraction injury, external displacement was applied to the transverse processes at C6 and C7 caudal to C5 by the actuator with the vertebral clamps after facetectomy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5035937&req=5

f1: Schematic diagrams of the three spinal cord injury (SCI) mechanisms. The spinal column orientation for (a) the normal animal and (b–d) the three SCI mechanisms is shown. To produce contusion injury, external displacement was applied to the dorsal spinal cord between C5 and C6 by an actuator with a 2-mm–diameter tip after laminectomy. To produce dislocation injury, external displacement was applied to the transverse processes at C6 and C7 dorsal to C5 by the actuator with vertebral clamps after facetectomy. To produce distraction injury, external displacement was applied to the transverse processes at C6 and C7 caudal to C5 by the actuator with the vertebral clamps after facetectomy.

Mentions: A cervical SCI was induced because of the preponderance of cervical injuries in clinical SCI.1,2 The animals' spinal columns from C2 to C7 were exposed dorsally by incision and splitting the muscles along the midline. Moderate contusion (n = 8), dislocation (n = 11), and distraction (n = 11) injuries were produced between C5 and C6 (Fig. 1) using our UBC multimechanism SCI apparatus as described previously.6,19,29 For contusion, the spinal cord between C5 and C6 was exposed by laminectomy. Custom vertebral clamps held the spinal column rigidly at the transverse processes on a stereotaxic surgical frame. An electromagnetic linear actuator applied a small pre-load to the surface of the dura mater (0.03 N) with a custom 2-mm–diameter tip. The injury was produced by retracting the actuator 6 mm above the dura mater and accelerating it into the spinal cord to a maximum displacement of 1.6 mm (Fig. 1b).


Differential Histopathological and Behavioral Outcomes Eight Weeks after Rat Spinal Cord Injury by Contusion, Dislocation, and Distraction Mechanisms
Schematic diagrams of the three spinal cord injury (SCI) mechanisms. The spinal column orientation for (a) the normal animal and (b–d) the three SCI mechanisms is shown. To produce contusion injury, external displacement was applied to the dorsal spinal cord between C5 and C6 by an actuator with a 2-mm–diameter tip after laminectomy. To produce dislocation injury, external displacement was applied to the transverse processes at C6 and C7 dorsal to C5 by the actuator with vertebral clamps after facetectomy. To produce distraction injury, external displacement was applied to the transverse processes at C6 and C7 caudal to C5 by the actuator with the vertebral clamps after facetectomy.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Schematic diagrams of the three spinal cord injury (SCI) mechanisms. The spinal column orientation for (a) the normal animal and (b–d) the three SCI mechanisms is shown. To produce contusion injury, external displacement was applied to the dorsal spinal cord between C5 and C6 by an actuator with a 2-mm–diameter tip after laminectomy. To produce dislocation injury, external displacement was applied to the transverse processes at C6 and C7 dorsal to C5 by the actuator with vertebral clamps after facetectomy. To produce distraction injury, external displacement was applied to the transverse processes at C6 and C7 caudal to C5 by the actuator with the vertebral clamps after facetectomy.
Mentions: A cervical SCI was induced because of the preponderance of cervical injuries in clinical SCI.1,2 The animals' spinal columns from C2 to C7 were exposed dorsally by incision and splitting the muscles along the midline. Moderate contusion (n = 8), dislocation (n = 11), and distraction (n = 11) injuries were produced between C5 and C6 (Fig. 1) using our UBC multimechanism SCI apparatus as described previously.6,19,29 For contusion, the spinal cord between C5 and C6 was exposed by laminectomy. Custom vertebral clamps held the spinal column rigidly at the transverse processes on a stereotaxic surgical frame. An electromagnetic linear actuator applied a small pre-load to the surface of the dura mater (0.03 N) with a custom 2-mm–diameter tip. The injury was produced by retracting the actuator 6 mm above the dura mater and accelerating it into the spinal cord to a maximum displacement of 1.6 mm (Fig. 1b).

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