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A consistent, quantifiable, and graded rat lumbosacral spinal cord injury model.

Wen J, Sun D, Tan J, Young W - J. Neurotrauma (2015)

Bottom Line: The result shows that peroneal and tibial motoneurons were respectively distributed in 4.71 mm and 5.01 mm columns in the spinal cord.Dropping a 10-g weight from 25 mm or 50 mm caused 1.5 mm or 3.75 mm gaps in peroneal and tibial motoneuronal columns, respectively, and increased spinal cord white matter loss.Fifty millimeter contusions significantly increased FL and reduced TS, ITS, STS, SITS, SFI, and SSI more than 25 mm contusions, and resulted in smaller axon and myelinated axon diameters in tibial and peroneal nerves and greater atrophy of gastrocnemius and anterior tibialis muscles, than 25 mm contusions.

View Article: PubMed Central - PubMed

Affiliation: 1 Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey , Piscataway, New Jersey.

ABSTRACT
The purpose of this study is to develop a rat lumbosacral spinal cord injury (SCI) model that causes consistent motoneuronal loss and behavior deficits. Most SCI models focus on the thoracic or cervical spinal cord. Lumbosacral SCI accounts for about one third of human SCI but no standardized lumbosacral model is available for evaluating therapies. Twenty-six adult female Sprague-Dawley rats were randomized to three groups: sham (n=9), 25 mm (n=8), and 50 mm (n=9). Sham rats had laminectomy only, while 25 mm and 50 mm rats were injured by dropping a 10 g rod from a height of 25 mm or 50 mm, respectively, onto the L4-5 spinal cord at the T13/L1 vertebral junction. We measured footprint length (FL), toe spreading (TS), intermediate toe spreading (ITS), and sciatic function index (SFI) from walking footprints, and static toe spreading (STS), static intermediate toe spreading (SITS), and static sciatic index (SSI) from standing footprints. At six weeks, we assessed neuronal and white matter loss, quantified axons, diameter, and myelin thickness in the peroneal and tibial nerves, and measured cross-sectional areas of tibialis anterior and gastrocnemius muscle fibers. The result shows that peroneal and tibial motoneurons were respectively distributed in 4.71 mm and 5.01 mm columns in the spinal cord. Dropping a 10-g weight from 25 mm or 50 mm caused 1.5 mm or 3.75 mm gaps in peroneal and tibial motoneuronal columns, respectively, and increased spinal cord white matter loss. Fifty millimeter contusions significantly increased FL and reduced TS, ITS, STS, SITS, SFI, and SSI more than 25 mm contusions, and resulted in smaller axon and myelinated axon diameters in tibial and peroneal nerves and greater atrophy of gastrocnemius and anterior tibialis muscles, than 25 mm contusions. This model of lumbosacral SCI produces consistent and graded loss of white matter, motoneuronal loss, peripheral nerve axonal changes, and anterior tibialis and gastrocnemius muscles atrophy in rats.

No MeSH data available.


Related in: MedlinePlus

Measurements of myelinated axons after surgery. (A–C) shows exemplary images of combined silver and fast blue staining of tibial nerve in the Sham, 25 mm, and 50 mm injury groups, respectively. Axons were stained black and surrounding myelin sheathes were stained blue. (D) shows the numbers of myelinated axon in tibial and peroneal nerves of the three injury groups. (E–G) are higher magnification images of tibial nerve in the Sham, 25 mm, and 50 mm, groups, respectively. Arrows indicate densely silver-stained axon bulbs. (H) shows mean axon diameters in the three injury groups. (I) shows myelin sheath thickness in the three injury groups. Scale bar (A–C), 100 μm; (E–G), 10 μm. The error bars (D, H, I) indicate standard deviation. * indicates p<0.05 versus Sham; # indicates p<0.05 versus 25 mm. The data represent means and standard errors of means from 3 rats from the Sham group and 4 rats each from the 25 mm and 50 mm groups.
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f7: Measurements of myelinated axons after surgery. (A–C) shows exemplary images of combined silver and fast blue staining of tibial nerve in the Sham, 25 mm, and 50 mm injury groups, respectively. Axons were stained black and surrounding myelin sheathes were stained blue. (D) shows the numbers of myelinated axon in tibial and peroneal nerves of the three injury groups. (E–G) are higher magnification images of tibial nerve in the Sham, 25 mm, and 50 mm, groups, respectively. Arrows indicate densely silver-stained axon bulbs. (H) shows mean axon diameters in the three injury groups. (I) shows myelin sheath thickness in the three injury groups. Scale bar (A–C), 100 μm; (E–G), 10 μm. The error bars (D, H, I) indicate standard deviation. * indicates p<0.05 versus Sham; # indicates p<0.05 versus 25 mm. The data represent means and standard errors of means from 3 rats from the Sham group and 4 rats each from the 25 mm and 50 mm groups.

Mentions: We assessed axons in the tibial and common peroneal nerves (Fig. 7). Profiles of collapsed axons surrounded by myelin sheaths were present in both nerves of rats injured by 25 mm or 50 mm contusions (Fig.7F, 7G). Total myelinated axon counts in tibial nerve were 3015.2±180.0 for the Sham group, 2939.4±144.1 for the 25 mm group, and 2852±145.7 for 50 mm group. Total myelinated axonal numbers in common peroneal nerve was 1007.6±133.6 for the Sham group, 967.4±88.3 for the 25 mm group, and 994.4±119.3 for the 50 mm group. ANOVA showed no significant differences of total myelinated axon numbers among the three groups (p>0.05) in either nerve.


A consistent, quantifiable, and graded rat lumbosacral spinal cord injury model.

Wen J, Sun D, Tan J, Young W - J. Neurotrauma (2015)

Measurements of myelinated axons after surgery. (A–C) shows exemplary images of combined silver and fast blue staining of tibial nerve in the Sham, 25 mm, and 50 mm injury groups, respectively. Axons were stained black and surrounding myelin sheathes were stained blue. (D) shows the numbers of myelinated axon in tibial and peroneal nerves of the three injury groups. (E–G) are higher magnification images of tibial nerve in the Sham, 25 mm, and 50 mm, groups, respectively. Arrows indicate densely silver-stained axon bulbs. (H) shows mean axon diameters in the three injury groups. (I) shows myelin sheath thickness in the three injury groups. Scale bar (A–C), 100 μm; (E–G), 10 μm. The error bars (D, H, I) indicate standard deviation. * indicates p<0.05 versus Sham; # indicates p<0.05 versus 25 mm. The data represent means and standard errors of means from 3 rats from the Sham group and 4 rats each from the 25 mm and 50 mm groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4492780&req=5

f7: Measurements of myelinated axons after surgery. (A–C) shows exemplary images of combined silver and fast blue staining of tibial nerve in the Sham, 25 mm, and 50 mm injury groups, respectively. Axons were stained black and surrounding myelin sheathes were stained blue. (D) shows the numbers of myelinated axon in tibial and peroneal nerves of the three injury groups. (E–G) are higher magnification images of tibial nerve in the Sham, 25 mm, and 50 mm, groups, respectively. Arrows indicate densely silver-stained axon bulbs. (H) shows mean axon diameters in the three injury groups. (I) shows myelin sheath thickness in the three injury groups. Scale bar (A–C), 100 μm; (E–G), 10 μm. The error bars (D, H, I) indicate standard deviation. * indicates p<0.05 versus Sham; # indicates p<0.05 versus 25 mm. The data represent means and standard errors of means from 3 rats from the Sham group and 4 rats each from the 25 mm and 50 mm groups.
Mentions: We assessed axons in the tibial and common peroneal nerves (Fig. 7). Profiles of collapsed axons surrounded by myelin sheaths were present in both nerves of rats injured by 25 mm or 50 mm contusions (Fig.7F, 7G). Total myelinated axon counts in tibial nerve were 3015.2±180.0 for the Sham group, 2939.4±144.1 for the 25 mm group, and 2852±145.7 for 50 mm group. Total myelinated axonal numbers in common peroneal nerve was 1007.6±133.6 for the Sham group, 967.4±88.3 for the 25 mm group, and 994.4±119.3 for the 50 mm group. ANOVA showed no significant differences of total myelinated axon numbers among the three groups (p>0.05) in either nerve.

Bottom Line: The result shows that peroneal and tibial motoneurons were respectively distributed in 4.71 mm and 5.01 mm columns in the spinal cord.Dropping a 10-g weight from 25 mm or 50 mm caused 1.5 mm or 3.75 mm gaps in peroneal and tibial motoneuronal columns, respectively, and increased spinal cord white matter loss.Fifty millimeter contusions significantly increased FL and reduced TS, ITS, STS, SITS, SFI, and SSI more than 25 mm contusions, and resulted in smaller axon and myelinated axon diameters in tibial and peroneal nerves and greater atrophy of gastrocnemius and anterior tibialis muscles, than 25 mm contusions.

View Article: PubMed Central - PubMed

Affiliation: 1 Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey , Piscataway, New Jersey.

ABSTRACT
The purpose of this study is to develop a rat lumbosacral spinal cord injury (SCI) model that causes consistent motoneuronal loss and behavior deficits. Most SCI models focus on the thoracic or cervical spinal cord. Lumbosacral SCI accounts for about one third of human SCI but no standardized lumbosacral model is available for evaluating therapies. Twenty-six adult female Sprague-Dawley rats were randomized to three groups: sham (n=9), 25 mm (n=8), and 50 mm (n=9). Sham rats had laminectomy only, while 25 mm and 50 mm rats were injured by dropping a 10 g rod from a height of 25 mm or 50 mm, respectively, onto the L4-5 spinal cord at the T13/L1 vertebral junction. We measured footprint length (FL), toe spreading (TS), intermediate toe spreading (ITS), and sciatic function index (SFI) from walking footprints, and static toe spreading (STS), static intermediate toe spreading (SITS), and static sciatic index (SSI) from standing footprints. At six weeks, we assessed neuronal and white matter loss, quantified axons, diameter, and myelin thickness in the peroneal and tibial nerves, and measured cross-sectional areas of tibialis anterior and gastrocnemius muscle fibers. The result shows that peroneal and tibial motoneurons were respectively distributed in 4.71 mm and 5.01 mm columns in the spinal cord. Dropping a 10-g weight from 25 mm or 50 mm caused 1.5 mm or 3.75 mm gaps in peroneal and tibial motoneuronal columns, respectively, and increased spinal cord white matter loss. Fifty millimeter contusions significantly increased FL and reduced TS, ITS, STS, SITS, SFI, and SSI more than 25 mm contusions, and resulted in smaller axon and myelinated axon diameters in tibial and peroneal nerves and greater atrophy of gastrocnemius and anterior tibialis muscles, than 25 mm contusions. This model of lumbosacral SCI produces consistent and graded loss of white matter, motoneuronal loss, peripheral nerve axonal changes, and anterior tibialis and gastrocnemius muscles atrophy in rats.

No MeSH data available.


Related in: MedlinePlus