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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

Walking footprint and analysis. (A–C) Pictures of typical footprints obtained at one week after injury in the Sham, 25 mm, and 50 mm groups, respectively. Scale bar (A-C), 10 mm. Dash line: Footprint length (FL), maximum distance from the third toe to end of the print; Toe spread (TS), distance between the first and fifth toes; Intermediate toe spread (ITS), distance from the second to the fourth toe. (D) The increase in mean footprint length (FL) in the Sham (n=8), 25 mm (n=7), and 50 mm (n=8) groups. (E) and (F) show the decrease in toe spread (TS) and intermediate toe spread (ITS) in the three injury groups. (G) shows the decrease in mean sciatic function index (SFI) scores. The error bars indicate standard deviation. The three groups differed significantly from each other at all time-points after the first week. * indicates significant difference compared with the Sham group. # indicates significant difference between 25 mm and 50 mm groups. (H) shows a walking injured rat (2 weeks after injury) while (I) shows a normal rat. Both rats had just moved their left hindlimb forward. The heel of injured rat (H red arrow) touched the ground, while normal one did not. The toes of injured rat (H blue arrow) did not flatten and spread, while the normal one did. Neither of these behaviors would be rated in a BBB score.
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f2: Walking footprint and analysis. (A–C) Pictures of typical footprints obtained at one week after injury in the Sham, 25 mm, and 50 mm groups, respectively. Scale bar (A-C), 10 mm. Dash line: Footprint length (FL), maximum distance from the third toe to end of the print; Toe spread (TS), distance between the first and fifth toes; Intermediate toe spread (ITS), distance from the second to the fourth toe. (D) The increase in mean footprint length (FL) in the Sham (n=8), 25 mm (n=7), and 50 mm (n=8) groups. (E) and (F) show the decrease in toe spread (TS) and intermediate toe spread (ITS) in the three injury groups. (G) shows the decrease in mean sciatic function index (SFI) scores. The error bars indicate standard deviation. The three groups differed significantly from each other at all time-points after the first week. * indicates significant difference compared with the Sham group. # indicates significant difference between 25 mm and 50 mm groups. (H) shows a walking injured rat (2 weeks after injury) while (I) shows a normal rat. Both rats had just moved their left hindlimb forward. The heel of injured rat (H red arrow) touched the ground, while normal one did not. The toes of injured rat (H blue arrow) did not flatten and spread, while the normal one did. Neither of these behaviors would be rated in a BBB score.

Mentions: Before injury, mean FLs were 20.1±0.95 mm, 23.04±1.26 mm, and 22.38±1.57 mm for the Sham, 25 mm, and 50 mm groups, respectively. Normally, rats walked with their heels elevated from the ground. After injury, as shown in Figure 2H, the rats walked with their heels on the ground and hence had longer footprints. At one week after injury, three of seven rats in Group 25 mm and four of eight rats in Group 50 mm could not take steps and their footprint lengths were assumed to be 45 mm. With these assumed values, mean footprint lengths of the 25 mm and 50 mm groups, respectively, increased to 39.89±5.88 mm and 40.33±5.07 mm (Fig. 2). By two weeks, all the rats were able to walk. Repeated ANOVA indicated significant differences among the groups (p<0.0001). Post hoc testing revealed significant differences between the Sham and 25 mm groups (p<0.0001), the Sham and 50 mm groups (p<0.0001), and the 25 mm and 50 mm groups (p=0.0023).


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

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

Walking footprint and analysis. (A–C) Pictures of typical footprints obtained at one week after injury in the Sham, 25 mm, and 50 mm groups, respectively. Scale bar (A-C), 10 mm. Dash line: Footprint length (FL), maximum distance from the third toe to end of the print; Toe spread (TS), distance between the first and fifth toes; Intermediate toe spread (ITS), distance from the second to the fourth toe. (D) The increase in mean footprint length (FL) in the Sham (n=8), 25 mm (n=7), and 50 mm (n=8) groups. (E) and (F) show the decrease in toe spread (TS) and intermediate toe spread (ITS) in the three injury groups. (G) shows the decrease in mean sciatic function index (SFI) scores. The error bars indicate standard deviation. The three groups differed significantly from each other at all time-points after the first week. * indicates significant difference compared with the Sham group. # indicates significant difference between 25 mm and 50 mm groups. (H) shows a walking injured rat (2 weeks after injury) while (I) shows a normal rat. Both rats had just moved their left hindlimb forward. The heel of injured rat (H red arrow) touched the ground, while normal one did not. The toes of injured rat (H blue arrow) did not flatten and spread, while the normal one did. Neither of these behaviors would be rated in a BBB score.
© Copyright Policy - open-access
Related In: Results  -  Collection

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f2: Walking footprint and analysis. (A–C) Pictures of typical footprints obtained at one week after injury in the Sham, 25 mm, and 50 mm groups, respectively. Scale bar (A-C), 10 mm. Dash line: Footprint length (FL), maximum distance from the third toe to end of the print; Toe spread (TS), distance between the first and fifth toes; Intermediate toe spread (ITS), distance from the second to the fourth toe. (D) The increase in mean footprint length (FL) in the Sham (n=8), 25 mm (n=7), and 50 mm (n=8) groups. (E) and (F) show the decrease in toe spread (TS) and intermediate toe spread (ITS) in the three injury groups. (G) shows the decrease in mean sciatic function index (SFI) scores. The error bars indicate standard deviation. The three groups differed significantly from each other at all time-points after the first week. * indicates significant difference compared with the Sham group. # indicates significant difference between 25 mm and 50 mm groups. (H) shows a walking injured rat (2 weeks after injury) while (I) shows a normal rat. Both rats had just moved their left hindlimb forward. The heel of injured rat (H red arrow) touched the ground, while normal one did not. The toes of injured rat (H blue arrow) did not flatten and spread, while the normal one did. Neither of these behaviors would be rated in a BBB score.
Mentions: Before injury, mean FLs were 20.1±0.95 mm, 23.04±1.26 mm, and 22.38±1.57 mm for the Sham, 25 mm, and 50 mm groups, respectively. Normally, rats walked with their heels elevated from the ground. After injury, as shown in Figure 2H, the rats walked with their heels on the ground and hence had longer footprints. At one week after injury, three of seven rats in Group 25 mm and four of eight rats in Group 50 mm could not take steps and their footprint lengths were assumed to be 45 mm. With these assumed values, mean footprint lengths of the 25 mm and 50 mm groups, respectively, increased to 39.89±5.88 mm and 40.33±5.07 mm (Fig. 2). By two weeks, all the rats were able to walk. Repeated ANOVA indicated significant differences among the groups (p<0.0001). Post hoc testing revealed significant differences between the Sham and 25 mm groups (p<0.0001), the Sham and 50 mm groups (p<0.0001), and the 25 mm and 50 mm groups (p=0.0023).

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