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.
Subject(s)
Disease Models, Animal , Pediatrics , Spinal Cord Injuries , Afferent Pathways/physiopathology , Animals , Animals, Newborn , Ankle/innervation , Electroencephalography/methods , Evoked Potentials, Somatosensory/physiology , Humans , Laminectomy/methods , Magnetic Resonance Imaging/methods , Neurologic Examination , Recovery of Function , Spinal Cord/pathology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/therapy , Swine , Time Factors , Walking/physiologyABSTRACT
PURPOSE: To compare relative reduction of retinal ganglion cell (RGC) function and retinal nerve fiber layer (RNFL) thickness in early glaucoma by means of steady-state pattern electroretinogram (PERG) and optical coherence tomography (OCT), respectively. METHODS: Eighty-four persons with suspected glaucoma due to disc abnormalities (GS: mean age 56.6 +/- 13.8 years, standard automated perimetry [SAP] mean deviation [MD] -0.58 +/- 1.34 dB) and 34 patients with early manifest glaucoma (EMG, mean age 65.9 +/- 10.7 years, SAP MD -2.7 +/- 4.5 dB) were tested with PERG and OCT. Both GS and EMG patients had small refractive errors, corrected visual acuity > or =20/25, and no systemic or retinal disease other than glaucoma. RESULTS: MDs from age-predicted normal values were larger for PERG amplitude (GS: -1.113 dB; EMG: -2.352 dB) compared with the PERG-matched RNFL thickness (GS: -0.217 dB; EMG: -0.725 dB). Deviations exceeding the lower 95% tolerance intervals of the normal population were more frequent for PERG amplitude (GS: 26%; EMG: 56%) than PERG-matched RNFL thickness (GS: 6%; EMG: 29%). CONCLUSIONS: In early glaucoma, reduction in RGC electrical activity exceeds the proportion expected from lost RGC axons, suggesting that a population of viable RGCs in the central retina is dysfunctional. By combining PERG and OCT it is, in principle, possible to obtain unique information on reduced responsiveness of viable RGCs.
