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. 2023 Mar 8:14:1136267.
doi: 10.3389/fneur.2023.1136267. eCollection 2023.

Integration of multiple prognostic predictors in a porcine spinal cord injury model: A further step closer to reality

Chao-Kai Hu  1   2 , Ming-Hong Chen  3   4 , Yao-Horng Wang  5 , Jui-Sheng Sun  6   7   8   9 , Chung-Yu Wu  10
Affiliations

Integration of multiple prognostic predictors in a porcine spinal cord injury model: A further step closer to reality

Chao-Kai Hu et al. Front Neurol. .

Abstract

Introduction: Spinal cord injury (SCI) is a devastating neurological disorder with an enormous impact on individual's life and society. A reliable and reproducible animal model of SCI is crucial to have a deeper understanding of SCI. We have developed a large-animal model of spinal cord compression injury (SCI) with integration of multiple prognostic factors that would have applications in humans.

Methods: Fourteen human-like sized pigs underwent compression at T8 by implantation of an inflatable balloon catheter. In addition to basic neurophysiological recording of somatosensory and motor evoked potentials, we introduced spine-to-spine evoked spinal cord potentials (SP-EPs) by direct stimulation and measured them just above and below the affected segment. A novel intraspinal pressure monitoring technique was utilized to measure the actual pressure on the cord. The gait and spinal MRI findings were assessed in each animal postoperatively to quantify the severity of injury.

Results: We found a strong negative correlation between the intensity of pressure applied to the spinal cord and the functional outcome (P < 0.0001). SP-EPs showed high sensitivity for real time monitoring of intraoperative cord damage. On MRI, the ratio of the high-intensity area to the cross-sectional of the cord was a good predictor of recovery (P < 0.0001).

Conclusion: Our balloon compression SCI model is reliable, predictable, and easy to implement. By integrating SP-EPs, cord pressure, and findings on MRI, we can build a real-time warning and prediction system for early detection of impending or iatrogenic SCI and improve outcomes.

Keywords: balloon compression; intraspinal pressure; magnetic resonance imaging; motor behavior; porcine model; spinal cord injury; spine-to-spine evoked potentials.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Diagram showing the experimental set-up. SSEP, somatosensory evoked potentials; MEP, motor evoked potentials.
Figure 2
Figure 2
(A) Plain lateral radiograph showing an upstream three-contact platinum catheter electrode (D-wave electrode), inserted epidurally in the cephalic direction (white arrows) via a T5 flavectomy. (B) A downstream D-wave wire (black arrows) is inserted in the caudal direction epidurally from this laminectomy window. The balloon, which has been inflated with a contrast medium, is located at the T8 level (white arrow).
Figure 3
Figure 3
Photographs showing the surgical site. (A) A widened T10 laminectomy was created as the injury site. A Foley catheter with pressure sensor apparatus was implanted epidurally in the cranial direction. (B) A Foley balloon catheter was mounted with a pressure transducer. (C) The position of the pressure sensor is precisely at the center of the balloon when inflated.
Figure 4
Figure 4
The Porcine Thoracic Injury Behavioral Scale (PTIBS). (A) PTIBS score 1, complete loss of active hindlimb movements. (B) PTIBS score 3, the rump and knee are lifted off the ground transiently with “weight-bearing extensions.” (C) PTIBS score 8, more than six steps can be taken with the knees fully extended but balance while walking is mildly impaired.
Figure 5
Figure 5
Determination of the extent of the trauma-induced region on magnetic resonance images. (A) Mid-sagittal T2-weighted image showing an intramedullary hyperintensity lesion (black arrow) indicating cord damage. (B) A segment of the maximal hyperintensity area in a transverse T2-weighted image. (C) The severity of the spinal cord injury is determined by comparing the hyperintense area (green circle) ratio to the total cross-sectional area of the spinal cord (yellow circle) using ImageJ software.
Figure 6
Figure 6
Pigs are grouped according to the recovery status of the animals' hind limbs after surgery. The graph shows a scatter plot to indicate the difference in the maximum ISP that the spinal cord suffered in each animal. ISP, intraspinal pressure; SCI, spinal cord injury.
Figure 7
Figure 7
MEPs and SP-EPs were recorded in pig 11. (A) The waveforms (RAPB) in the upper part of the figure represent MEPs from the forelimb of the pig, which maintains a complete structure during the experiment. The waveforms in the lower part represented hindlimb MEPs (RAH). As the compression increases, the waveform declines gradually, resulting in a complete loss when the maximum compression pressure is reached. (B) As the compression increases, there is an initial prolongation of SP-EP latency which is followed by a decrease in amplitude. At this point, the balloon was released, and the amplitude decreased by 50% from the maximum pressure recorded. MEPs, motor evoked potentials; SP-Eps, spine-to-spine evoked spinal cord potentials.
Figure 8
Figure 8
SP-EPs in pig 14. MEPs could not be tested under inhaled general anesthesia. The SP-EP latency started to become prolonged when the ISP reached 6 mmHg. At this point, inflation ceased, and the balloon was released at an ISP of 18 mmHg before the amplitude dropped. ISP, intraspinal pressure; MEPs, motor evoked potentials; SP-Eps, spine-to-spine evoked spinal cord potentials.
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