Cerebrospinal fluid pressures during dynamic contusion-type spinal cord injury in a pig model

Jones, C. F.<sup>1,3</sup>; Lee, J. H. T.<sup>3</sup>; Kwon, B. K.<sup>2,3</sup>; Cripton, P. A.<sup>1,3</sup>

Affiliations

¹Orthopaedic and Injury Biomechanics Group, Departments of Mechanical Engineering and Orthopaedics

²Division of Spine, Department of Orthopaedics, The University of British Columbia, Vancouver, Canada

³International Collaboration on Repair Discoveries, The University of British Columbia, Vancouver, Canada

Abstract

Despite considerable effort over the last four decades, research has failed to translate into tangible and consistently effective treatment options for spinal cord injury (SCI). This is partly attributed to differences between the human injury response and that of the predominant rodent models. We hypothesized that some of this divergence could be because humans have a discernable cerebrospinal fluid (CSF) layer surrounding their spinal cord, while rodents do not. Therefore, we sought to characterize the fluid impulse induced in the CSF by experimental SCIs of low and high human-like severity, and to compare this with previous studies in which fluid impulse has been associated with neural tissue injury. We used a new in vivo pig model (n=6 per injury group, mean age 124.5 days, 20.9 kg) incorporating four miniature pressure transducers that were implanted in pairs in the subarachnoid space, cranial and caudal to the injury at 30 mm and 100 mm. The median peak impact force was 20.8 and 62.1 N, and the impact velocity, 2.3 and 4.7 m/s, for the low and high injury severities, respectively. The peak pressures near the injury had median values of 522.5 and 868.8 mmHg (range 96.7-1430.0) and far from the injury, 7.6 and 36.3 mmHg (range 3.8-83.7), for the respective injury groups. Pressure impulse, wave speed and attenuation factor were also evaluated. The data indicates that the severity and extent of primary tissue damage close to the injury site may be affected by a fluid pressure wave in the human-like CSF-spinal cord system. However, the pressure wave was considerably damped at 100 mm from the injury, reaching close to normal physiologic pressures. This study provides evidence that future work seeking to elucidate the mechanical origins of primary tissue damage in SCI should consider utilizing an animal or computational model that incorporates CSF. Further, this pig model may provide a valuable addition to the preclinical experimental process due to its similarities to human scaling, including the existence of a human-like CSF fluid layer.

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