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, 25 (10), 1227-40

Spinal Cord Contusion Based on Precise Vertebral Stabilization and Tissue Displacement Measured by Combined Assessment to Discriminate Small Functional Differences

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Spinal Cord Contusion Based on Precise Vertebral Stabilization and Tissue Displacement Measured by Combined Assessment to Discriminate Small Functional Differences

Yi Ping Zhang et al. J Neurotrauma.

Abstract

Contusive spinal cord injury (SCI) is the most common type of spinal injury seen clinically. Several rat contusion SCI models have been described, and all have strengths and weaknesses with respect to sensitivity, reproducibility, and clinical relevance. We developed the Louisville Injury System Apparatus (LISA), which contains a novel spine-stabilizing device that enables precise and stable spine fixation, and is based on tissue displacement to determine the severity of injury. Injuries graded from mild to moderately severe were produced using 0.2-, 0.4-, 0.6-, 0.8-, 1.0-, and 1.2-mm spinal cord displacement in rats. Basso, Beattie, and Bresnahan (BBB) and Louisville Swim Score (LSS) could not significantly distinguish between 0.2-mm lesion severities, except those of 0.6- and 0.8-mm BBB scores, but could between 0.4-mm injury differences or if the data were grouped (0.2-0.4, 0.6-0.8, and 1.0-1.2). Transcranial magnetic motor evoked potential (tcMMEP) response amplitudes were decreased 10-fold at 0.2-mm displacement, barely detected at 0.4-mm displacement, and absent with greater displacement injuries. In contrast, somatosensory evoked potentials (SSEPs) were recorded at 0.2- and 0.4-mm displacements with normal amplitudes and latencies but were detected at lower amplitudes at 0.6-mm displacement and absent with more severe injuries. Analyzing combined BBB, tcMMEP, and SSEP results enabled statistically significant discrimination between 0.2-, 0.4-, 0.6-, and 0.8-mm displacement injuries but not the more severe injuries. Present data document that the LISA produces reliable and reproducible SCI whose parameters of injury can be adjusted to more accurately reflect clinical SCI. Moreover, multiple outcome measures are necessary to accurately detect small differences in functional deficits and/or recovery. This is of crucial importance when trying to detect functional improvement after therapeutic intervention to treat SCI.

Figures

FIG. 1.
FIG. 1.
(Top) The LISA consists of the following: (1) impactor complex that measures tissue displacement and causes the contusion, (2) spine stabilizer that secures the spinal cord, (3) vibration isolator that prevents vibration from being transmitted from the impactor complex to the force sensor located below the spine stabilizer, (4) base, and (5) control box that contains circuits that control the impactor position and its duration of contact with the spinal cord. It also conveys biomechanical information to the impactor complex. (Bottom) Cartoons of the impactor complex illustrate the mechanism of tissue displacement control. In position A, the distance from the laser sensor (pink vertical line) to the reflecting surface (DRS) of the impactor is calibrated in its fully extended position (vertical large arrow). Tip distance (TD) = tip thickness (3 mm) + DRS. In position B, the impactor is withdrawn and moved laterally away from the laser beam path (horizontal large arrow). The distance from the laser sensor to the spinal cord is measured (cord distance [CD]). The desired tissue displacement is determined by the difference between the cord distance and tip distance (CD-TD). The impactor is returned back to the laser beam path and is ready for impact.
FIG. 2.
FIG. 2.
(A) Picture of the rat spine stabilizer. Note the shape of the two arms (one is fixed and the other adjustable), which provides excellent bone fixation. The three main components of the spine stabilizing device include a U-shaped steel channel to hold the animal, a fixed arm, and an adjustable arm. In this figure, the fixed arm is set in one of the cervical (C) grooves while the adjustable arm is not yet attached. For thoracic injuries, the thoracic (T) grooves are utilized. The animal is secured into the rat spine stabilizer by inserting the stainless steel arms of the stabilizer bilaterally on the facets of T8 and then locking the set screws. This device suspends the spine to prevent respiration and other movements from influencing the spine position. (B) The effectiveness of vertebral stabilization was studied on the NYU device that monitors the vertebral position and the spinal cord surface. Using the LISA spine stabilization device, a 12.5-g-cm injury did not cause bone movement and, after impact, the deformed spinal cord recoiled back to the original position (solid lines). However, attaching forceps to the spinous processes as the fixation method results in significant vertebral and spinal cord shift (dotted lines).
FIG. 3.
FIG. 3.
Injury parameters were monitored including impactor/cord contact duration (msec), impactor velocity at impact (m/sec), and force (V) at impact.
FIG. 4.
FIG. 4.
(A) Open field locomotor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) score for each group subjected to the displacement injury with a velocity of 1 m/sec and impactor/cord contact time of 0.2 sec. Greater tissue displacements led to poorer functional recovery. At each greater displacement level, the BBB score was progressively lower which continued over 5 weeks. (B) The Louisville Swim Score (LSS) was used to test rats at 5 weeks after spinal cord injury (SCI). Swimming performance worsened with increasing cord displacement. After 5 weeks, the milder injury displacement groups were able to swim much better than those injured at 0.8 mm or higher displacement levels (***p = 0.001). Data are the mean ± SD (n = 6–7/group).
FIG. 5.
FIG. 5.
Neither increased velocity nor increased duration of cord-impactor contact had an effect on the outcome of locomotor function. All three injury conditions (velocity 1 m/sec, duration 0.2 sec [filled circles]; velocity 1 m/sec, duration 5.0 sec [inverted filled triangles]; velocity 2 m/sec, duration 0.2 sec [open circles]) showed improvement over time (*p > 0.05). There were no significant differences at any time points between the three groups. Data are the mean ± SD (n = 6/group).
FIG. 6.
FIG. 6.
Transcranial magnetic motor evoked potentials (tcMMEPs) and somatosensory evoked potentials (SSEPs) could be recorded in all animals before surgery. (A) Representative tcMMEP waveforms of a normal animal (displacement = 0 mm) are compared to responses following graded spinal cord injury (SCI). Responses are very sensitive to injury severity (displacement > 0.2 mm). (B) SSEPs were recorded in all rats using low-intensity electrical stimulation to the posterior tibial nerve (PTN). Representative waveforms of the responses show deterioration after spinal cord contusion. Compared with the uninjured spinal cord (displacement = 0 mm), the P1 latency (arrowhead) was longer in all injury groups with a response (p < 0.01). A decreased amplitude was noted in the 0.6-mm displacement group (p = 0.058; n = 5–6/group).
FIG. 7.
FIG. 7.
There was greater tissue loss as displacement injury increased: 0-mm (A), 0.2-mm (B), 0.4-mm (C), 0.6-mm (D), 0.8-mm (E), 1.0-mm (F), and 1.2-mm (G) displacement (iron-eriochrome cyanine RC staining). Higher velocity (2 m/sec; H) and longer duration of cord-impactor contact (5 sec; I) did not show a difference in white matter (WM) sparing compared with the 0.6-mm displacement. (J) There was a greater degree of white matter sparing among the 0.2- and 0.4-mm groups compared to the higher displacement groups (p < 0.001). Data are the mean ± SD (n = 5–6/group).
FIG. 8.
FIG. 8.
The amount of spared white matter at the epicenter correlated to behavior outcome and injury parameters. Spared white matter at the epicenter was plotted against week 5 post-injury results: (A) Basso, Beattie, and Bresnahan (BBB) scores. (B) Louisville Swim Score (LSS) scores. (C) Tissue displacement. (D) Impact force. BBB (p < 0.001, n = 31) and LSS (p < 0.001, n = 31) correlated positively, and tissue displacement (p < 0.001, n = 31) and impact force (p < 0.05, n = 27) correlated inversely with white matter sparing (rs, Spearman rank; r, Pearson correlation). Individual data points are shown.
FIG. 9.
FIG. 9.
Representation of tissue displacement, velocity, and force during impact. Tissue displacement is constant and therefore can be precisely controlled (arrow, upper panel). Velocity decelerates throughout the contact period (middle panel). Force increased and peaked before the impactor stopped (lower panel). Controllable parameters (displacement) create a more reproducible injury than variable parameters (velocity, force).

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