Attenuated Tissue Damage With Mechanical Tissue Resuscitation in a Pig Model of Spinal Cord Injury.

Abstract

Our previous studies on the treatment of spinal cord injuries with Mechanical Tissue Resuscitation (MTR) in rats have demonstrated that it can significantly improve the locomotor recovery and Basso Beattie Bresnahan scores. MTR treatment also reduced fluid accumulations by T2-imaging and improved the mean neural fiber number and fiber length in injured sites by fiber tractography. Myelin volume was also significantly preserved by MTR treatment. For further clinical application, a large animal model is necessary to assess this treatment. This study examined the effects of application of MTR on traumatic spinal cord injury in a swine model. Traumatic spinal cord contusion injuries in swine were created by controlled pneumatic impact device. Negative pressure at -75 mm Hg was continuously applied to the injured site through open cell silicone manifold for 7 days. In vivo magnetic resonance imaging for T2 and gradient echo (GRE) analysis employed a 3T machine, while a 7T machine was employed for diffusion tensor imaging (DTI) and fiber tractography. Histological hematoxylin and eosin (H&E) and Luxol fast blue staining were examined. MTR significantly reduced the mean injured volumes over 46% by T2-imaging in the injured sites from 477.34 ± 146.31 mm3 in non-treated group to 255.99 ± 70.28 mm3 in MTR treated group (p < 0.01). It also reduced fluid accumulations by relative T2 signal density in the epicenter of the spinal cord injury from 1.62 ± 0.27 in non-treated group to 1.22 ± 0.10 in the MTR treated group (p < 0.05). The mean injured tissue volume measured by H&E staining was 303.71 ± 78.21 mm3 in the non-treated group and decreased significantly to 162.16 ± 33.0 mm3 in the MTR treated group (p < 0.01). The myelin fiber bundles stained by Luxol blue were preserved much more in the MTR treated group (90 ± 29.71 mm3) than in the non-treated group (33.68 ± 24.99 mm3, p < 0.01). The fractional anisotropy (FA) values processed by DTI analysis are increased from 0.203 ± 0.027 in the untreated group to 0.238 ± 0.029 in MTR treatment group (p < 0.05). Fiber tractography showings the mean fiber numbers across the impacted area were increased over 112% from 327.0 ± 99.74 in the non-treated group to 694.83 ± 297.86 in the MTR treated group (p < 0.05). These results indicate local application of MTR for 7 days to spinal cord injury in a swine model decreased tissue injury, reduced tissue edema, and preserved more myelin fibers as well as nerve fibers in the injured spinal cord.