PURPOSE: To evaluate the neuroprotective effect of combination therapy of polyethylene glycol (PEG) and magnesium sulfate (MgSO4) after a spinal cord injury. MATERIALS AND METHODS: Twenty Sprague Dawley male rats (300-350 gm) had a spinal cord injury after T9/10 laminectomy using an Ohio State University (OSU) impactor under intraperitoneal anesthesia. The animals were randomized to receive either PEG (1 g/kg)+MgSO4 (300 mg/kg) or saline (2 ml) via carotid vein after 2 hours of injury and then every 6 hours for 5 times. The behavioral outcome assessments were performed on days 2, 4 and 7, and then every week using the Basso, Bresnahan, and Beattie (BBB) score and subscore. The animals also underwent sensory threshold testing using a von Frey monofilament device and gait analysis with Catwalk program before and 6 weeks after cord injury. The animals were sacrificed at the end of 6 weeks and histologic assessment was performed to measure the areas of white and gray matter. RESULTS: For the animals treated with PEG+MgSO4 and saline, the mean BBB scores at 6 weeks post-injury were 13.3+/-0.3, 11.4+/-0.2 and the BBB subscores were 9.1+/-1.1, 4.4+/-1.2 respectively (p<0.05). No significant differences were found in sensory testing and gait analysis between the two groups. Histologic assessment revealed no significant difference in gray matter sparing but the areas of white matter at the lesion epicenter were 0.68+/-0.2, 0.41+/-0.04 mm2 in the PEG+MgSO4 and saline groups respectively, which indicated significant sparing of white matter in PEG+MgSO4 group (p<0.05). CONCLUSION: The combination therapy of polyethylene glycol and magnesium sulfate improved the motor function and showed significant histological sparing of the spinal cord after an acute spinal cord injury in rats.
Anesthesia ; Animals ; Gait ; Humans ; Laminectomy ; Magnesium ; Magnesium Sulfate ; Male ; Neuroprotective Agents ; Ohio ; Polyethylene ; Polyethylene Glycols ; Rats ; Sensory Thresholds ; Spinal Cord ; Spinal Cord Injuries ; Veins

Traumatic spinal cord injury (SCI) research has recently focused on the use of rat and mouse models for in vivo SCI experiments. Such small rodent SCI models are invaluable for the field, and much has been discovered about the biologic and physiologic aspects of SCI from these models. It has been difficult, however, to reproduce the efficacy of treatments found to produce neurologic benefits in rodent SCI models when these treatments are tested in human clinical trials. A large animal model may have advantages for translational research where anatomical, physiological, or genetic similarities to humans may be more relevant for pre-clinically evaluating novel therapies. Here, we review the work carried out at the University of British Columbia (UBC) on a large animal model of SCI that utilizes Yucatan miniature pigs. The UBC porcine model of SCI may be a useful intermediary in the pre-clinical testing of novel pharmacological treatments, cell-based therapies, and the “bedside back to bench” translation of human clinical observations, which require preclinical testing in an applicable animal model.
Animals ; British Columbia ; Humans ; Mice ; Models, Animal ; Rats ; Rodentia ; Spinal Cord Injuries ; Spinal Cord ; Swine ; Translational Medical Research

PURPOSE: To evaluate the neuroprotective effect of statins after a spinal cord injury. MATERIALS AND METHODS: Twenty four Sprague Dawley rats had a spinal cord injury at T9/10 using an Ohio State University (OSU) impactor. The animals were randomized to receive either simvastatin, atorvastatin, or saline with oral gavage everyday for 7 days. A behavioral outcome assessment was performed on days 2, 4 and 7, and then every week using the Basso, Bresnahan, and Beattie (BBB) score and subscore. The animals also underwent sensory threshold testing using a von Frey monofilament device. The animals were sacrificed at the end of 6 weeks and a spinal cord specimen was harvested. Histology and immunohistochemistry were performed to measure the areas of white and gray matter, and the sparing of oligodenrocytes. RESULTS: For the animals treated with simvastatin, atorvastatin and saline, the mean BBB scores at 6 weeks post-injury was 13.2+/-0.1, 11.8+/-0.5, and 11.3+/-0.2 and the BBB subscores were 9.2+/-1.1, 4.8+/-1.8 and 4.4+/-1.4 respectively (p<0.05). The areas of white matter at the lesion epicenter were 0.78+/-0.05, 0.5+/-0.18 and 0.41+/-0.03 mm2 in the simvastatin, atorvastatin and saline groups respectively, and the number of spared oligodendrocytes was significantly higher in the simvastatin treated animals (p<0.05). CONCLUSION: The simvastatin treatment improved the behavior and histological sparing of the spinal cord after an acute spinal cord injury in rats.
Animals ; Heptanoic Acids ; Humans ; Immunohistochemistry ; Neuroprotective Agents ; Ohio ; Oligodendroglia ; Pyrroles ; Rats, Sprague-Dawley ; Sensory Thresholds ; Simvastatin ; Spinal Cord ; Spinal Cord Injuries ; Atorvastatin Calcium