Pediatric spinal cord injury in infant piglets: description of a new large animal model and review of the literature

Abstract

Objective: To develop a new, clinically relevant large animal model of pediatric spinal cord injury (SCI) and compare the clinical and experimental features of pediatric SCI.

Methods: Infant piglets (3-5 weeks old) underwent contusive SCI by controlled cortical impactor at T7. Severe complete SCI was induced in 6 piglets, defined as SCI with no spontaneous return of sensorimotor function. Eight piglets received incomplete SCI, which was followed by partial recovery. Somatosensory evoked potentials, magnetic resonance imaging, neurobehavioral function, and histopathology were measured during a 28-day survival period.

Results: Mean SCI volume (defined as volume of necrotic tissue) was larger after complete compared with incomplete SCI (387 +/- 29 vs 77 +/- 38 mm3, respectively, P < 0.001). No functional recovery occurred after complete SCI. After incomplete SCI, piglets initially had an absence of lower extremity sensorimotor function, urinary and stool retention, and little to no rectal tone. Sensory responses recovered first (1-2 days after injury), followed by spontaneous voiding, lower extremity motor responses, regular bowel movements, and repetitive flexion-extension of the lower extremities when crawling. No piglet recovered spontaneous walking, although 4 of 8 animals with incomplete injuries were able to bear weight by 28 days. In vivo magnetic resonance imaging was performed safely, yielded high-resolution images of tissue injury, and correlated closely with injury volume seen on histopathology, which included intramedullary hemorrhage, cellular inflammation, necrosis, and apoptosis.

Conclusion: Piglets performed well as a reproducible model of traumatic pediatric SCI in a large animal with chronic survival and utilizing multiple outcome measures, including evoked potentials, magnetic resonance imaging, functional outcome scores, and histopathology.

Figure 1

Acute histopathology 6 hours after complete (A) and incomplete (B and C) spinal cord injury (SCI). High-resolution T2-weighted ex vivo magnetic resonance image is shown in C. Tissue destruction is evident throughout the thickness of the thoracic cord after complete SCI. White matter is considerably more spared after incomplete SCI, with partial dorsal column injury and primarily central zone of injury, inflammation, and hemorrhage.

Figure 2

High-power views of histopathology 3 days after incomplete spinal cord injury in an infant piglet. Marked inflammatory cell infiltrate (A, large arrow) and moderately high number of apoptotic cells (B, small arrows, caspase-3 positive) are seen in the border zone between injury and normal-appearing spinal cord.

Figure 3

Representative longitudinal sections of thoracic spinal cord stained with Luxol fast blue 28 days after complete (A–C) and incomplete (D–F) spinal cord injury (SCI). Chronic lesion size is significantly greater in thickness and length after complete compared with incomplete SCI.

Figure 4

T1-weighted fluid-attenuated inversion recovery magnetic resonance images 2 hours after incomplete spinal cord injury.

Figure 5

Serial T2-weighted in vivo magnetic resonance image of incomplete spinal cord injury in an infant piglet.

Figure 6

Functional recovery in piglets (n  =  8) after incomplete spinal cord injury (SCI) over 28-day survival period. In most cases, outcome reached a plateau 14 days after SCI. Sensory function recovered completely in all animals but motor recovery did not. (See Appendix for details of the neurologic examination).

Figure 7

Somatosensory evoked potentials before and after incomplete spinal cord injury.