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Research Papers

Cerebrospinal Fluid Pressures Resulting From Experimental Traumatic Spinal Cord Injuries in a Pig Model

[+] Author and Article Information
Claire F. Jones

Orthopaedic and Injury Biomechanics Group,
Departments of Mechanical Engineering
and Orthopaedics,
University of British Columbia,
Vancouver, BC V5Z 1M9, Canada;
International Collaboration on Repair
Discoveries (ICORD),
University of British Columbia,
Vancouver, BC V5Z 1M9, Canada
e-mail: claire.jones@alumni.ubc.ca

Jae H. T. Lee

e-mail: jaelee@icord.org

Uri Burstyn

e-mail: burstyn@icord.org

Elena B. Okon

e-mail: okon@icord.org
International Collaboration on Repair
Discoveries (ICORD),
University of British Columbia,
Vancouver, BC V5Z 1M9, Canada

Brian K. Kwon

Associate Professor
Combined Neurosurgical and Orthopaedic
Spine Program (CNOSP),
Department of Orthopaedics,
University of British Columbia,
Vancouver, BC V5Z 1M9, Canada;
International Collaboration on Repair
Discoveries (ICORD),
University of British Columbia,
Vancouver, BC V5Z 1M9, Canada
e-mail: brian.kwon@vch.ca

Peter A. Cripton

Orthopaedic and Injury Biomechanics Group,
Departments of Mechanical Engineering
and Orthopaedics,
University of British Columbia,
Vancouver, BC V5Z 1M9, Canada;
International Collaboration on Repair
Discoveries (ICORD),
University of British Columbia,
Vancouver, BC V5Z 1M9, Canada
e-mail: cripton@mech.ubc.ca

1Corresponding author. Address all correspondences to 818 W 10th Avenue, Blusson Spinal Cord Centre, Vancouver, BC V5Z 1M9, Canada.

Contributed by the Bioengineering Division of ASME for publication in the Journal of Biomechanical Engineering. Manuscript received May 14, 2012; final manuscript received May 9, 2013; accepted manuscript posted July 29, 2013; published online September 20, 2013. Assoc. Editor: Tim David.

J Biomech Eng 135(10), 101005 (Sep 20, 2013) (10 pages) Paper No: BIO-12-1190; doi: 10.1115/1.4025100 History: Received May 14, 2012; Revised May 09, 2013; Accepted July 29, 2013

Despite considerable effort over the last four decades, research has failed to translate into consistently effective treatment options for spinal cord injury (SCI). This is partly attributed to differences between the injury response of humans and rodent models. Some of this difference could be because the cerebrospinal fluid (CSF) layer of the human spine is relatively large, while that of the rodents is extremely thin. We sought to characterize the fluid impulse induced in the CSF by experimental SCIs of moderate 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. Tissue sparing was assessed with Eriochrome Cyanine and Neutral Red staining. The median peak pressures near the injury were 522.5 and 868.8 mmHg (range 96.7–1430.0) and far from the injury were 7.6 and 36.3 mmHg (range 3.8–83.7), for the moderate and high injury severities, respectively. Pressure impulse (mmHg.ms), apparent wave speed, and apparent attenuation factor were also evaluated. The data indicates that the fluid pressure wave may be sufficient to affect the severity and extent of primary tissue damage close to the injury site. However, the CSF pressure was close to normal physiologic values at 100 mm from the injury. The high injury severity animals had less tissue sparing than the moderate injury severity animals; this difference was statistically significant only within 1.6 mm of the epicenter. These results indicate that future research seeking to elucidate the mechanical origins of primary tissue damage in SCI should consider the effects of CSF. This pig model provides advantages for basic and preclinical SCI research due to its similarities to human scale, including the existence of a human-like CSF fluid layer.

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Figures

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Fig. 2

Photo (top) and overlay (bottom) indicating the location of the four intrathecal pressure transducers and pedicle screws

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Fig. 1

Schematic of front view (left) and side view (right) of the weight-drop injury device installed on vertebra T10-T13 (not to scale)

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Fig. 3

Typical response for a single injury (#P1805); CSF pressure at four locations, and load. Peak pressure and load are indicated by open circles; impulse calculation bounds for load, cranial, and caudal pressures are indicated by closed diamonds, closed triangles and open triangles, respectively.

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Fig. 4

Peak positive CSF pressure and pressure impulse at each transducer location, for the two injury groups. Bar is median value, error bars are 25th percentile/75th percentile. * indicates statistical significance (p < 0.05).

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Fig. 5

White and gray matter sparing (%) for the high, moderate, and sham animals (left) and cumulative white and gray matter sparing from 8 mm cranial and caudal of the epicenter (right). Data are presented as median ±25th/75th percentile. * indicates significant difference (p < 0.05) between the high and moderate injury severity as per Mann-Whitney U-test. Sham animals are shown but no statistics were performed on this group due to low numbers.

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