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

Micrographs of myelinated axons in the (a) lateral white matter and (b) ventral white matter. Representative confocal micrographs of the regions of interest used in the quantitative analysis of white matter damage immunostained for neurofilament H/β-tubulin (NF/Tub) for axons (in red) and myelin basic protein for myelin/myelin debris in green. The normal control tracts show a dense packing of predominantly midsize myelinated axons in the lateral white matter and predominantly medium to large ones in the ventral white matter. These intact fibers display the typical green myelin rings surrounding a red axon in the middle. All three injury types produce a thinning of the myelinated axon packing in the lateral white matter at all levels reflecting the damage of ascending and descending fibers while the damage of the ventral white matter is very pronounced at the injury epicenter and further distally (with some preservation rostrally). The damage of the lateral white matter is somewhat more pronounced after dislocation than in the other two models. Note the abundance of green dots or empty rings representing myelin debris and of red dots without green rings most likely showing demyelinated (and possibly sprouted) axons; they appear particularly prominent in the lateral white matter around the epicenter after distraction injury. Scale bar 20 μm. MBP, myelin basic protein.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Micrographs of myelinated axons in the (a) lateral white matter and (b) ventral white matter. Representative confocal micrographs of the regions of interest used in the quantitative analysis of white matter damage immunostained for neurofilament H/β-tubulin (NF/Tub) for axons (in red) and myelin basic protein for myelin/myelin debris in green. The normal control tracts show a dense packing of predominantly midsize myelinated axons in the lateral white matter and predominantly medium to large ones in the ventral white matter. These intact fibers display the typical green myelin rings surrounding a red axon in the middle. All three injury types produce a thinning of the myelinated axon packing in the lateral white matter at all levels reflecting the damage of ascending and descending fibers while the damage of the ventral white matter is very pronounced at the injury epicenter and further distally (with some preservation rostrally). The damage of the lateral white matter is somewhat more pronounced after dislocation than in the other two models. Note the abundance of green dots or empty rings representing myelin debris and of red dots without green rings most likely showing demyelinated (and possibly sprouted) axons; they appear particularly prominent in the lateral white matter around the epicenter after distraction injury. Scale bar 20 μm. MBP, myelin basic protein.

Mentions: In the lateral white matter, there was a lower density of myelinated axons at the epicenter after the distraction injury compared with contusion injury (Fig. 5c). We observed large numbers of small myelinated and unmyelinated axons (apparently spared or possibly demyelinated) at all levels post-contusion injury in the lateral white matter (Fig. 7a). In contrast, after dislocation, numerous axons were devoid of myelin and likely demyelinated based on their large caliber. Although the number of myelinated axons encountered in the lateral white matter after distraction was low at the lesion epicenter, there was an abundance of unmyelinated and apparently demyelinated axons (based on their large caliber).


Differential Histopathological and Behavioral Outcomes Eight Weeks after Rat Spinal Cord Injury by Contusion, Dislocation, and Distraction Mechanisms
Micrographs of myelinated axons in the (a) lateral white matter and (b) ventral white matter. Representative confocal micrographs of the regions of interest used in the quantitative analysis of white matter damage immunostained for neurofilament H/β-tubulin (NF/Tub) for axons (in red) and myelin basic protein for myelin/myelin debris in green. The normal control tracts show a dense packing of predominantly midsize myelinated axons in the lateral white matter and predominantly medium to large ones in the ventral white matter. These intact fibers display the typical green myelin rings surrounding a red axon in the middle. All three injury types produce a thinning of the myelinated axon packing in the lateral white matter at all levels reflecting the damage of ascending and descending fibers while the damage of the ventral white matter is very pronounced at the injury epicenter and further distally (with some preservation rostrally). The damage of the lateral white matter is somewhat more pronounced after dislocation than in the other two models. Note the abundance of green dots or empty rings representing myelin debris and of red dots without green rings most likely showing demyelinated (and possibly sprouted) axons; they appear particularly prominent in the lateral white matter around the epicenter after distraction injury. Scale bar 20 μm. MBP, myelin basic protein.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Micrographs of myelinated axons in the (a) lateral white matter and (b) ventral white matter. Representative confocal micrographs of the regions of interest used in the quantitative analysis of white matter damage immunostained for neurofilament H/β-tubulin (NF/Tub) for axons (in red) and myelin basic protein for myelin/myelin debris in green. The normal control tracts show a dense packing of predominantly midsize myelinated axons in the lateral white matter and predominantly medium to large ones in the ventral white matter. These intact fibers display the typical green myelin rings surrounding a red axon in the middle. All three injury types produce a thinning of the myelinated axon packing in the lateral white matter at all levels reflecting the damage of ascending and descending fibers while the damage of the ventral white matter is very pronounced at the injury epicenter and further distally (with some preservation rostrally). The damage of the lateral white matter is somewhat more pronounced after dislocation than in the other two models. Note the abundance of green dots or empty rings representing myelin debris and of red dots without green rings most likely showing demyelinated (and possibly sprouted) axons; they appear particularly prominent in the lateral white matter around the epicenter after distraction injury. Scale bar 20 μm. MBP, myelin basic protein.
Mentions: In the lateral white matter, there was a lower density of myelinated axons at the epicenter after the distraction injury compared with contusion injury (Fig. 5c). We observed large numbers of small myelinated and unmyelinated axons (apparently spared or possibly demyelinated) at all levels post-contusion injury in the lateral white matter (Fig. 7a). In contrast, after dislocation, numerous axons were devoid of myelin and likely demyelinated based on their large caliber. Although the number of myelinated axons encountered in the lateral white matter after distraction was low at the lesion epicenter, there was an abundance of unmyelinated and apparently demyelinated axons (based on their large caliber).

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