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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

The behavioral test data for the animals injured by the three spinal cord injury mechanisms. Data are presented as median with quartiles and offset horizontally for clarity. The time goes from −1 week (pre-injury) to +8 weeks (post-injury). All statistical differences reported are p < 0.05. (a) Martinez locomotor rating scale, forelimb score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +6 week; distraction +1 to +6 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (b) Martinez locomotor rating scale, hindlimb score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: +8 weeks; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: +8 weeks. (c) Martinez locomotor rating scale, total score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (d) Forelimb locomotor assessment scale score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +4 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (e) Grooming test score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: +1 to +8 weeks; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: +2 to +8 weeks. (f) Grip strength test statistical results: (i) differences from −1 week: contusion +2 weeks; dislocation +2 weeks; distraction +2 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: +3, +6, +8 wk; (iv) differences between dislocation and distraction: +3 to +8 weeks.
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f10: The behavioral test data for the animals injured by the three spinal cord injury mechanisms. Data are presented as median with quartiles and offset horizontally for clarity. The time goes from −1 week (pre-injury) to +8 weeks (post-injury). All statistical differences reported are p < 0.05. (a) Martinez locomotor rating scale, forelimb score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +6 week; distraction +1 to +6 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (b) Martinez locomotor rating scale, hindlimb score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: +8 weeks; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: +8 weeks. (c) Martinez locomotor rating scale, total score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (d) Forelimb locomotor assessment scale score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +4 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (e) Grooming test score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: +1 to +8 weeks; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: +2 to +8 weeks. (f) Grip strength test statistical results: (i) differences from −1 week: contusion +2 weeks; dislocation +2 weeks; distraction +2 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: +3, +6, +8 wk; (iv) differences between dislocation and distraction: +3 to +8 weeks.

Mentions: We observed differences across the three SCI mechanisms in the various post-injury behavioral tests. In the Martinez locomotor rating scale, the forelimb score for all animals decreased at 1 week post-injury (Fig. 10a). After that time, the contusion and distraction animals improved up to 8 weeks post-injury and reached levels similar to those before SCI, while the dislocation animals did not improve beyond 1 week. As expected, after the incomplete cervical injuries used in our models, the impairments in hindlimb function as measured with this scale were of a transient nature in rats, but the hindlimb score did not improve after all three SCIs from 1–8 weeks post-injury, and the animals remained below pre-injury score (Fig. 10b). The total score decreased at 1 week post-injury and then improved to 8 weeks (Fig. 10c), but the animals for all three SCI mechanisms still had lower total scores at 8 weeks post-injury than pre-injury, mainly because of impairment of the forelimb movements. The FLAS mirrored the results of the Martinez total score (Fig. 10d).


Differential Histopathological and Behavioral Outcomes Eight Weeks after Rat Spinal Cord Injury by Contusion, Dislocation, and Distraction Mechanisms
The behavioral test data for the animals injured by the three spinal cord injury mechanisms. Data are presented as median with quartiles and offset horizontally for clarity. The time goes from −1 week (pre-injury) to +8 weeks (post-injury). All statistical differences reported are p < 0.05. (a) Martinez locomotor rating scale, forelimb score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +6 week; distraction +1 to +6 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (b) Martinez locomotor rating scale, hindlimb score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: +8 weeks; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: +8 weeks. (c) Martinez locomotor rating scale, total score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (d) Forelimb locomotor assessment scale score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +4 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (e) Grooming test score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: +1 to +8 weeks; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: +2 to +8 weeks. (f) Grip strength test statistical results: (i) differences from −1 week: contusion +2 weeks; dislocation +2 weeks; distraction +2 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: +3, +6, +8 wk; (iv) differences between dislocation and distraction: +3 to +8 weeks.
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f10: The behavioral test data for the animals injured by the three spinal cord injury mechanisms. Data are presented as median with quartiles and offset horizontally for clarity. The time goes from −1 week (pre-injury) to +8 weeks (post-injury). All statistical differences reported are p < 0.05. (a) Martinez locomotor rating scale, forelimb score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +6 week; distraction +1 to +6 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (b) Martinez locomotor rating scale, hindlimb score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: +8 weeks; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: +8 weeks. (c) Martinez locomotor rating scale, total score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (d) Forelimb locomotor assessment scale score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +4 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: none. (e) Grooming test score statistical results: (i) differences from −1 week: contusion +1 to +8 weeks; dislocation +1 to +8 weeks; distraction +1 to +8 weeks; (ii) differences between contusion and dislocation: +1 to +8 weeks; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: +2 to +8 weeks. (f) Grip strength test statistical results: (i) differences from −1 week: contusion +2 weeks; dislocation +2 weeks; distraction +2 to +8 weeks; (ii) differences between contusion and dislocation: none; (iii) differences between contusion and distraction: +3, +6, +8 wk; (iv) differences between dislocation and distraction: +3 to +8 weeks.
Mentions: We observed differences across the three SCI mechanisms in the various post-injury behavioral tests. In the Martinez locomotor rating scale, the forelimb score for all animals decreased at 1 week post-injury (Fig. 10a). After that time, the contusion and distraction animals improved up to 8 weeks post-injury and reached levels similar to those before SCI, while the dislocation animals did not improve beyond 1 week. As expected, after the incomplete cervical injuries used in our models, the impairments in hindlimb function as measured with this scale were of a transient nature in rats, but the hindlimb score did not improve after all three SCIs from 1–8 weeks post-injury, and the animals remained below pre-injury score (Fig. 10b). The total score decreased at 1 week post-injury and then improved to 8 weeks (Fig. 10c), but the animals for all three SCI mechanisms still had lower total scores at 8 weeks post-injury than pre-injury, mainly because of impairment of the forelimb movements. The FLAS mirrored the results of the Martinez total score (Fig. 10d).

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