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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 total spinal cord area and areas of spared tissue from the Luxol fast blue (LFB)-stained sections. Cross-sectional area of (a) total spinal cord, (b) spared tissue of the total white matter, (c) spared tissue of the lateral white matter, (d) spared tissue of the dorsal white matter, (e) spared tissue of the ventral white matter, and (f) spared tissue of the gray matter for the different SCI mechanisms (n = 6) and the normal (n = 5) as quantified from LFB-stained sections. Values for spared tissue analysis were obtained by measuring the number of pixels that were darker than the background intensity. All data are presented as median with quartiles and offset horizontally for clarity. The position along the spinal cord extends from −5 mm (rostral) through +5 mm (caudal) from the epicenter (0 mm). All statistical differences reported are p < 0.05. Statistical results in (a): (i) differences from normal: contusion −5 to +1 mm, +5 mm; dislocation −5 to +5 mm; distraction none; (ii) differences between contusion and dislocation: −5, −3, −1.6, −0.2 mm; (iii) differences between contusion and distraction: −3 to +2.2 mm; (iv) differences between dislocation and distraction: −5 to +3 mm. Statistical results in (b): (i) differences from normal: contusion −1 to +1 mm; dislocation −3, to +1 mm; distraction none; (ii) differences between contusion and dislocation: −5, −1.6, −0.2 mm; (iii) differences between contusion and distraction: −3 to +1.6 mm; (iv) differences between dislocation and distraction: −3 to +1.6 mm. Statistical results in (c): (i) differences from normal: contusion −1, +3 mm; dislocation −3 to +3 mm; distraction 0, +3 mm; (ii) differences between contusion and dislocation: −2.2 to +1 mm; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: −1.6 to +1 mm. Statistical results in (d): (i) differences from normal: contusion −1 to +1 mm; dislocation −3, −1, 0 mm; distraction −5 to +5 mm; (ii) differences between contusion and dislocation: +5 mm; (iii) differences between contusion and distraction: −5 to +5 mm; (iv) differences between dislocation and distraction: −5 to +5 mm. Statistical results in (e): (i) differences from normal: contusion 0, +1 mm; dislocation 0 mm; distraction +1 mm; (ii) differences between contusion and dislocation: −5 mm; (iii) differences between contusion and distraction: −1 to +0.6 mm, +3 mm; (iv) differences between dislocation and distraction: −1 to +0.6 mm. Statistical results in (f): (i) differences from normal: contusion −1 to +3 mm; dislocation −5mm, −1 to +3 mm; distraction 0, +1 mm; (ii) differences between contusion and dislocation: −5 mm; (iii) differences between contusion and distraction: −2.2 to +2.2 mm; (iv) differences between dislocation and distraction: −5 to +2.2 mm.
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f4: The total spinal cord area and areas of spared tissue from the Luxol fast blue (LFB)-stained sections. Cross-sectional area of (a) total spinal cord, (b) spared tissue of the total white matter, (c) spared tissue of the lateral white matter, (d) spared tissue of the dorsal white matter, (e) spared tissue of the ventral white matter, and (f) spared tissue of the gray matter for the different SCI mechanisms (n = 6) and the normal (n = 5) as quantified from LFB-stained sections. Values for spared tissue analysis were obtained by measuring the number of pixels that were darker than the background intensity. All data are presented as median with quartiles and offset horizontally for clarity. The position along the spinal cord extends from −5 mm (rostral) through +5 mm (caudal) from the epicenter (0 mm). All statistical differences reported are p < 0.05. Statistical results in (a): (i) differences from normal: contusion −5 to +1 mm, +5 mm; dislocation −5 to +5 mm; distraction none; (ii) differences between contusion and dislocation: −5, −3, −1.6, −0.2 mm; (iii) differences between contusion and distraction: −3 to +2.2 mm; (iv) differences between dislocation and distraction: −5 to +3 mm. Statistical results in (b): (i) differences from normal: contusion −1 to +1 mm; dislocation −3, to +1 mm; distraction none; (ii) differences between contusion and dislocation: −5, −1.6, −0.2 mm; (iii) differences between contusion and distraction: −3 to +1.6 mm; (iv) differences between dislocation and distraction: −3 to +1.6 mm. Statistical results in (c): (i) differences from normal: contusion −1, +3 mm; dislocation −3 to +3 mm; distraction 0, +3 mm; (ii) differences between contusion and dislocation: −2.2 to +1 mm; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: −1.6 to +1 mm. Statistical results in (d): (i) differences from normal: contusion −1 to +1 mm; dislocation −3, −1, 0 mm; distraction −5 to +5 mm; (ii) differences between contusion and dislocation: +5 mm; (iii) differences between contusion and distraction: −5 to +5 mm; (iv) differences between dislocation and distraction: −5 to +5 mm. Statistical results in (e): (i) differences from normal: contusion 0, +1 mm; dislocation 0 mm; distraction +1 mm; (ii) differences between contusion and dislocation: −5 mm; (iii) differences between contusion and distraction: −1 to +0.6 mm, +3 mm; (iv) differences between dislocation and distraction: −1 to +0.6 mm. Statistical results in (f): (i) differences from normal: contusion −1 to +3 mm; dislocation −5mm, −1 to +3 mm; distraction 0, +1 mm; (ii) differences between contusion and dislocation: −5 mm; (iii) differences between contusion and distraction: −2.2 to +2.2 mm; (iv) differences between dislocation and distraction: −5 to +2.2 mm.

Mentions: Geometrical change of the spinal cord was observed after both contusion injury and dislocation injury (Fig. 3), with the total spinal cord cross-sectional areas being less than the control animals at and around the epicenter (Fig. 4a). The cross-sectional areas after dislocation were less than after contusion, rostral to the injury site. In contrast, the cross-sectional area of distraction-injured cords was larger than after both contusion and dislocation (Fig. 3, 4a), but was not different from controls.


Differential Histopathological and Behavioral Outcomes Eight Weeks after Rat Spinal Cord Injury by Contusion, Dislocation, and Distraction Mechanisms
The total spinal cord area and areas of spared tissue from the Luxol fast blue (LFB)-stained sections. Cross-sectional area of (a) total spinal cord, (b) spared tissue of the total white matter, (c) spared tissue of the lateral white matter, (d) spared tissue of the dorsal white matter, (e) spared tissue of the ventral white matter, and (f) spared tissue of the gray matter for the different SCI mechanisms (n = 6) and the normal (n = 5) as quantified from LFB-stained sections. Values for spared tissue analysis were obtained by measuring the number of pixels that were darker than the background intensity. All data are presented as median with quartiles and offset horizontally for clarity. The position along the spinal cord extends from −5 mm (rostral) through +5 mm (caudal) from the epicenter (0 mm). All statistical differences reported are p < 0.05. Statistical results in (a): (i) differences from normal: contusion −5 to +1 mm, +5 mm; dislocation −5 to +5 mm; distraction none; (ii) differences between contusion and dislocation: −5, −3, −1.6, −0.2 mm; (iii) differences between contusion and distraction: −3 to +2.2 mm; (iv) differences between dislocation and distraction: −5 to +3 mm. Statistical results in (b): (i) differences from normal: contusion −1 to +1 mm; dislocation −3, to +1 mm; distraction none; (ii) differences between contusion and dislocation: −5, −1.6, −0.2 mm; (iii) differences between contusion and distraction: −3 to +1.6 mm; (iv) differences between dislocation and distraction: −3 to +1.6 mm. Statistical results in (c): (i) differences from normal: contusion −1, +3 mm; dislocation −3 to +3 mm; distraction 0, +3 mm; (ii) differences between contusion and dislocation: −2.2 to +1 mm; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: −1.6 to +1 mm. Statistical results in (d): (i) differences from normal: contusion −1 to +1 mm; dislocation −3, −1, 0 mm; distraction −5 to +5 mm; (ii) differences between contusion and dislocation: +5 mm; (iii) differences between contusion and distraction: −5 to +5 mm; (iv) differences between dislocation and distraction: −5 to +5 mm. Statistical results in (e): (i) differences from normal: contusion 0, +1 mm; dislocation 0 mm; distraction +1 mm; (ii) differences between contusion and dislocation: −5 mm; (iii) differences between contusion and distraction: −1 to +0.6 mm, +3 mm; (iv) differences between dislocation and distraction: −1 to +0.6 mm. Statistical results in (f): (i) differences from normal: contusion −1 to +3 mm; dislocation −5mm, −1 to +3 mm; distraction 0, +1 mm; (ii) differences between contusion and dislocation: −5 mm; (iii) differences between contusion and distraction: −2.2 to +2.2 mm; (iv) differences between dislocation and distraction: −5 to +2.2 mm.
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f4: The total spinal cord area and areas of spared tissue from the Luxol fast blue (LFB)-stained sections. Cross-sectional area of (a) total spinal cord, (b) spared tissue of the total white matter, (c) spared tissue of the lateral white matter, (d) spared tissue of the dorsal white matter, (e) spared tissue of the ventral white matter, and (f) spared tissue of the gray matter for the different SCI mechanisms (n = 6) and the normal (n = 5) as quantified from LFB-stained sections. Values for spared tissue analysis were obtained by measuring the number of pixels that were darker than the background intensity. All data are presented as median with quartiles and offset horizontally for clarity. The position along the spinal cord extends from −5 mm (rostral) through +5 mm (caudal) from the epicenter (0 mm). All statistical differences reported are p < 0.05. Statistical results in (a): (i) differences from normal: contusion −5 to +1 mm, +5 mm; dislocation −5 to +5 mm; distraction none; (ii) differences between contusion and dislocation: −5, −3, −1.6, −0.2 mm; (iii) differences between contusion and distraction: −3 to +2.2 mm; (iv) differences between dislocation and distraction: −5 to +3 mm. Statistical results in (b): (i) differences from normal: contusion −1 to +1 mm; dislocation −3, to +1 mm; distraction none; (ii) differences between contusion and dislocation: −5, −1.6, −0.2 mm; (iii) differences between contusion and distraction: −3 to +1.6 mm; (iv) differences between dislocation and distraction: −3 to +1.6 mm. Statistical results in (c): (i) differences from normal: contusion −1, +3 mm; dislocation −3 to +3 mm; distraction 0, +3 mm; (ii) differences between contusion and dislocation: −2.2 to +1 mm; (iii) differences between contusion and distraction: none; (iv) differences between dislocation and distraction: −1.6 to +1 mm. Statistical results in (d): (i) differences from normal: contusion −1 to +1 mm; dislocation −3, −1, 0 mm; distraction −5 to +5 mm; (ii) differences between contusion and dislocation: +5 mm; (iii) differences between contusion and distraction: −5 to +5 mm; (iv) differences between dislocation and distraction: −5 to +5 mm. Statistical results in (e): (i) differences from normal: contusion 0, +1 mm; dislocation 0 mm; distraction +1 mm; (ii) differences between contusion and dislocation: −5 mm; (iii) differences between contusion and distraction: −1 to +0.6 mm, +3 mm; (iv) differences between dislocation and distraction: −1 to +0.6 mm. Statistical results in (f): (i) differences from normal: contusion −1 to +3 mm; dislocation −5mm, −1 to +3 mm; distraction 0, +1 mm; (ii) differences between contusion and dislocation: −5 mm; (iii) differences between contusion and distraction: −2.2 to +2.2 mm; (iv) differences between dislocation and distraction: −5 to +2.2 mm.
Mentions: Geometrical change of the spinal cord was observed after both contusion injury and dislocation injury (Fig. 3), with the total spinal cord cross-sectional areas being less than the control animals at and around the epicenter (Fig. 4a). The cross-sectional areas after dislocation were less than after contusion, rostral to the injury site. In contrast, the cross-sectional area of distraction-injured cords was larger than after both contusion and dislocation (Fig. 3, 4a), but was not different from controls.

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