Development of a large-animal model to measure dynamic cerebrospinal fluid pressure during spinal cord injury

Laboratory investigation

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Object

Spinal cord injury (SCI) often results in considerable permanent neurological impairment, and unfortunately, the successful translation of effective treatments from laboratory models to human patients is lacking. This may be partially attributed to differences in anatomy, physiology, and scale between humans and rodent models. One potentially important difference between the rodent and human spinal cord is the presence of a significant CSF volume within the intrathecal space around the human cord. While the CSF may “cushion” the spinal cord, pressure waves within the CSF at the time of injury may contribute to the extent and severity of the primary injury. The objective of this study was to develop a model of contusion SCI in a miniature pig and establish the feasibility of measuring spinal CSF pressure during injury.

Methods

A custom weight-drop device was used to apply thoracic contusion SCI to 17 Yucatan miniature pigs. Impact load and velocity were measured. Using fiber optic pressure transducers implanted in the thecal sac, CSF pressures resulting from 2 injury severities (caused by 50-g and 100-g weights released from a 50-cm height) were measured.

Results

The median peak impact loads were 54 N and 132 N for the 50-g and 100-g injuries, respectively. At a nominal 100 mm from the injury epicenter, the authors observed a small negative pressure peak (median −4.6 mm Hg [cranial] and −5.8 mm Hg [caudal] for 50 g; −27.6 mm Hg [cranial] and −27.2 mm Hg [caudal] for 100 g) followed by a larger positive pressure peak (median 110.5 mm Hg [cranial] and 77.1 mm Hg [caudal] for 50 g; 88.4 mm Hg [cranial] and 67.2 mm Hg [caudal] for 100 g) relative to the preinjury pressure. There were no significant differences in peak pressure between the 2 injury severities or the caudal and cranial transducer locations.

Conclusions

A new model of contusion SCI was developed to measure spinal CSF pressures during the SCI event. The results suggest that the Yucatan miniature pig is an appropriate model for studying CSF, spinal cord, and dura interactions during injury. With further development and characterization it may be an appropriate in vivo largeanimal model of SCI to answer questions regarding pathological changes, therapeutic safety, or treatment efficacy, particularly where humanlike dimensions and physiology are important.

Abbreviations used in this paper:IM = intramuscularly; SCI = spinal cord injury.

Article Information

Address correspondence to: Claire F. Jones, Ph.D., Biomechanics Laboratory, Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, British Columbia V5Z 1M9, Canada. email: claire.jones@alumni.ubc.ca.

Please include this information when citing this paper: published online April 20, 2012; DOI: 10.3171/2012.3.SPINE11970.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Photograph of the components of the modified weight-drop injury device. Inset: Close-up view of the load cell installed within the weight base, above the spherical impactor tip.

  • View in gallery

    Schematic of front view (left) and side view (right) of the weight-drop device installed over 4 vertebrae (not to scale).

  • View in gallery

    Upper: Photograph showing the surgical site, with 4 pressure transducers implanted intrathecally, a widened laminectomy at the injury site, and pedicle screws in T-9 and T-12. Lower: The same photograph with an overlay indicating locations of pressure transducer tips relative to the injury site (circle). The 2 “near” transducers were only implanted in 2 of the Group C animals.

  • View in gallery

    Graphs showing CSF pressure (CSFP) measured at the cranial-far (A) and caudal-far (B) transducers and load (C) for the Group B (50-g injury) animals. Zero time is arbitrarily aligned at caudal-far = ±3 mm Hg. There were no significant differences between the peak pressures (positive and negative) measured at the cranial-far and caudal-far locations. The early rise of the impact force, relative to the CSF pressure, for P1219 may indicate contact between the impactor and the sides of the laminectomy prior to dura contact. ms = milliseconds.

  • View in gallery

    Graphs showing CSF pressure measured at the cranial-far (A) and caudal-far (B) transducers and load (C) for the Group C (100-g injury) animals. Zero time is arbitrarily aligned at caudal-far = ±3 mm Hg. There were no significant differences between the peak pressures (positive and negative) measured at the cranial-far and caudal-far locations. There was considerable variability in the pressure profiles; for example, P1242 showed very little pressure change while P1264 exhibited a large fluctuation, yet the impact force profiles are fairly similar.

  • View in gallery

    Graphs showing CSF pressures for the 2 tests performed in Group C in which 2 “near” transducers were implanted (top: P1242; bottom: P1262). The pressures at the “near” location exceeded the upper range of the pressure transducers.

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