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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

Scatterplots showing the relation between histological and behavioral outcomes (n = 18, except in the Montoya staircase, n = 17) evaluated by Pearson correlation coefficient (r). The number of myelinated axons was measured by multiplying the density of myelinated axons by the area of spared tissue in the dorsal, lateral, and ventral white matter. The average of these numbers were then calculated between 5 mm rostral and caudal to the epicenter. The number of dorsal and large ventral cells was averaged between 1 mm rostral and 0.6 mm caudal and between 2.2 mm rostral and 1.6 mm caudal to the epicenter, respectively. These cord segments in histology were selectively analyzed because the injury differences were found within these distances relative to the epicenter. Behavioral data were obtained from the Martinez locomotor rating scale, the forelimb locomotor assessment scale, the grooming test, the grip strength test, and the Montoya staircase 8 week post-injury. *Statistically correlated with each other (p < 0.05).
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f11: Scatterplots showing the relation between histological and behavioral outcomes (n = 18, except in the Montoya staircase, n = 17) evaluated by Pearson correlation coefficient (r). The number of myelinated axons was measured by multiplying the density of myelinated axons by the area of spared tissue in the dorsal, lateral, and ventral white matter. The average of these numbers were then calculated between 5 mm rostral and caudal to the epicenter. The number of dorsal and large ventral cells was averaged between 1 mm rostral and 0.6 mm caudal and between 2.2 mm rostral and 1.6 mm caudal to the epicenter, respectively. These cord segments in histology were selectively analyzed because the injury differences were found within these distances relative to the epicenter. Behavioral data were obtained from the Martinez locomotor rating scale, the forelimb locomotor assessment scale, the grooming test, the grip strength test, and the Montoya staircase 8 week post-injury. *Statistically correlated with each other (p < 0.05).

Mentions: Scatterplots between the various histological outcomes and the behavioral scores are displayed in Figure 11, and many significant correlations were found. Significant relationships may shed a causal link between the structures in the spinal cord and certain behaviors, but we are cautious to not make too many assertions here, because it is a highly complex system that would likely require a much larger study and a multivariate statistical analysis. A second observation from these plots is the apparent clustering of the data from the three SCI mechanisms in some plots. An example is the grip strength—average number of dorsal cells scatterplot. This may demonstrate how the different SCI mechanisms result in distinct functional injuries.


Differential Histopathological and Behavioral Outcomes Eight Weeks after Rat Spinal Cord Injury by Contusion, Dislocation, and Distraction Mechanisms
Scatterplots showing the relation between histological and behavioral outcomes (n = 18, except in the Montoya staircase, n = 17) evaluated by Pearson correlation coefficient (r). The number of myelinated axons was measured by multiplying the density of myelinated axons by the area of spared tissue in the dorsal, lateral, and ventral white matter. The average of these numbers were then calculated between 5 mm rostral and caudal to the epicenter. The number of dorsal and large ventral cells was averaged between 1 mm rostral and 0.6 mm caudal and between 2.2 mm rostral and 1.6 mm caudal to the epicenter, respectively. These cord segments in histology were selectively analyzed because the injury differences were found within these distances relative to the epicenter. Behavioral data were obtained from the Martinez locomotor rating scale, the forelimb locomotor assessment scale, the grooming test, the grip strength test, and the Montoya staircase 8 week post-injury. *Statistically correlated with each other (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f11: Scatterplots showing the relation between histological and behavioral outcomes (n = 18, except in the Montoya staircase, n = 17) evaluated by Pearson correlation coefficient (r). The number of myelinated axons was measured by multiplying the density of myelinated axons by the area of spared tissue in the dorsal, lateral, and ventral white matter. The average of these numbers were then calculated between 5 mm rostral and caudal to the epicenter. The number of dorsal and large ventral cells was averaged between 1 mm rostral and 0.6 mm caudal and between 2.2 mm rostral and 1.6 mm caudal to the epicenter, respectively. These cord segments in histology were selectively analyzed because the injury differences were found within these distances relative to the epicenter. Behavioral data were obtained from the Martinez locomotor rating scale, the forelimb locomotor assessment scale, the grooming test, the grip strength test, and the Montoya staircase 8 week post-injury. *Statistically correlated with each other (p < 0.05).
Mentions: Scatterplots between the various histological outcomes and the behavioral scores are displayed in Figure 11, and many significant correlations were found. Significant relationships may shed a causal link between the structures in the spinal cord and certain behaviors, but we are cautious to not make too many assertions here, because it is a highly complex system that would likely require a much larger study and a multivariate statistical analysis. A second observation from these plots is the apparent clustering of the data from the three SCI mechanisms in some plots. An example is the grip strength—average number of dorsal cells scatterplot. This may demonstrate how the different SCI mechanisms result in distinct functional injuries.

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