Chronic spinal compression model in minipigs: a systematic behavioral, qualitative, and quantitative neuropathological study.
The goal of the present study was to develop a porcine spinal cord injury (SCI) model, and to describe the neurological outcome and characterize the corresponding quantitative and qualitative histological changes at 4-9 months after injury. Adult Gottingen-Minnesota minipigs were anesthetized and placed in a spine immobilization frame. The exposed T12 spinal segment was compressed in a dorso-ventral direction using a 5-mm-diameter circular bar with a progressively increasing peak force (1.5, 2.0, or 2.5 kg) at a velocity of 3 cm/sec. During recovery, motor and sensory function were periodically monitored. After survival, the animals were perfusion fixed and the extent of local SCI was analyzed by (1) post-mortem MRI analysis of dissected spinal cords, (2) qualitative and quantitative analysis of axonal survival at the epicenter of injury, and (3) defining the presence of local inflammatory changes, astrocytosis, and schwannosis. Following 2.5-kg spinal cord compression the animals demonstrated a near complete loss of motor and sensory function with no recovery over the next 4-9 months. Those that underwent spinal cord compression with 2 kg force developed an incomplete injury with progressive partial neurological recovery characterized by a restricted ability to stand and walk. Animals injured with a spinal compression force of 1.5 kg showed near normal ambulation 10 days after injury. In fully paralyzed animals (2.5 kg), MRI analysis demonstrated a loss of spinal white matter integrity and extensive septal cavitations. A significant correlation between the magnitude of loss of small and medium-sized myelinated axons in the ventral funiculus and neurological deficits was identified. These data, demonstrating stable neurological deficits in severely injured animals, similarities of spinal pathology to humans, and relatively good post-injury tolerance of this strain of minipigs to spinal trauma, suggest that this model can successfully be used to study therapeutic interventions targeting both acute and chronic stages of SCI.
Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), San Diego, California, USA.
Roman
R
Navarro
Stefan
S
Juhas
Sassan
S
Keshavarzi
Jana
J
Juhasova
Jan
J
Motlik
Karl
K
Johe
Silvia
S
Marsala
Miriam
M
Scadeng
Peter
P
Lazar
Zoltan
Z
Tomori
Gery
G
Schulteis
Michael
M
Beattie
Joseph D
JD
Ciacci
Martin
M
Marsala
D001003:Anal Canal / Q000502:physiology; D000818:Animals; D001369:Axons / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology*; D002908:Chronic Disease; D005260:Female; D006930:Hyperalgesia / Q000523:psychology; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009068:Movement / Q000502:physiology; D009122:Muscle Hypertonia / Q000503:physiopathology; D010147:Pain Measurement; D010264:Paraplegia / Q000473:pathology / Q000523:psychology; D010812:Physical Stimulation; D020127:Recovery of Function / Q000502:physiology; D012677:Sensation / Q000502:physiology; D013116:Spinal Cord / Q000473:pathology*; D013117:Spinal Cord Compression / Q000473:pathology* / Q000523:psychology*; D013552:Swine; D013556:Swine, Miniature; D013595:Syringomyelia / Q000473:pathology; D016707:Tissue Fixation