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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

Counts of spared NeuN-stained motoneurons. (A) Normal spinal cord. Large motoneurons are located in the ventral horn. (B) Injured spinal cord in Group 50 mm about 3 mm proximal to injury epicenter. (C) Injury epicenter in Group 50 mm. (D) Injured spinal cord in Group 50 mm about 3 mm distal to injury epicenter. Scale bar (A-D), 200 μm. (E) Graph of the numbers of spare motoneurons of±5 mm of the injury epicenter in the Sham (n=4), 25 mm (n=3), and 50 mm (n=4) injury groups. The error bars indicate standard deviation.
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f4: Counts of spared NeuN-stained motoneurons. (A) Normal spinal cord. Large motoneurons are located in the ventral horn. (B) Injured spinal cord in Group 50 mm about 3 mm proximal to injury epicenter. (C) Injury epicenter in Group 50 mm. (D) Injured spinal cord in Group 50 mm about 3 mm distal to injury epicenter. Scale bar (A-D), 200 μm. (E) Graph of the numbers of spare motoneurons of±5 mm of the injury epicenter in the Sham (n=4), 25 mm (n=3), and 50 mm (n=4) injury groups. The error bars indicate standard deviation.

Mentions: To assess motoneuronal loss, we counted NeuN-stained cells that met the criteria for motoneurons in coronal sections (i.e., located in ventral horn) with a clearly identifiable nucleus and a cell soma larger than 100 μm2 (Fig. 4). In the Sham group, the number of motoneurons declined from 20–25/section at the T13 vertebral level to 15–20/section at the L1 vertebra level. Injury caused complete loss of motoneurons at the lesion epicenter (Fig. 4C), gradually returning to levels similar to the Sham group at 5 mm rostral and caudal. Repeated measures ANOVA indicated significant difference of spared motoneurons among the three injury groups (p<0.0001). Post hoc testing revealed significant differences between Groups Sham and 25 mm (p<0.0001), Groups Sham and 50 mm (p<0.0001); and Groups 25 mm and 50 mm (p=0.0004).


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

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

Counts of spared NeuN-stained motoneurons. (A) Normal spinal cord. Large motoneurons are located in the ventral horn. (B) Injured spinal cord in Group 50 mm about 3 mm proximal to injury epicenter. (C) Injury epicenter in Group 50 mm. (D) Injured spinal cord in Group 50 mm about 3 mm distal to injury epicenter. Scale bar (A-D), 200 μm. (E) Graph of the numbers of spare motoneurons of±5 mm of the injury epicenter in the Sham (n=4), 25 mm (n=3), and 50 mm (n=4) injury groups. The error bars indicate standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4492780&req=5

f4: Counts of spared NeuN-stained motoneurons. (A) Normal spinal cord. Large motoneurons are located in the ventral horn. (B) Injured spinal cord in Group 50 mm about 3 mm proximal to injury epicenter. (C) Injury epicenter in Group 50 mm. (D) Injured spinal cord in Group 50 mm about 3 mm distal to injury epicenter. Scale bar (A-D), 200 μm. (E) Graph of the numbers of spare motoneurons of±5 mm of the injury epicenter in the Sham (n=4), 25 mm (n=3), and 50 mm (n=4) injury groups. The error bars indicate standard deviation.
Mentions: To assess motoneuronal loss, we counted NeuN-stained cells that met the criteria for motoneurons in coronal sections (i.e., located in ventral horn) with a clearly identifiable nucleus and a cell soma larger than 100 μm2 (Fig. 4). In the Sham group, the number of motoneurons declined from 20–25/section at the T13 vertebral level to 15–20/section at the L1 vertebra level. Injury caused complete loss of motoneurons at the lesion epicenter (Fig. 4C), gradually returning to levels similar to the Sham group at 5 mm rostral and caudal. Repeated measures ANOVA indicated significant difference of spared motoneurons among the three injury groups (p<0.0001). Post hoc testing revealed significant differences between Groups Sham and 25 mm (p<0.0001), Groups Sham and 50 mm (p<0.0001); and Groups 25 mm and 50 mm (p=0.0004).

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