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Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury.

ABSTRACT: Primates are an important and unique animal resource. We have developed a nonhuman primate model of spinal cord injury (SCI) to expand our knowledge of normal primate motor function, to assess the impact of disease and injury on sensory and motor function, and to test candidate therapies before they are applied to human patients. The lesion model consists of a lateral spinal cord hemisection at the C7 spinal level with subsequent examination of behavioral, electrophysiological, and anatomical outcomes. Results to date have revealed significant neuroanatomical and functional differences between rodents and primates that impact the development of candidate therapies. Moreover, these findings suggest the importance of testing some therapeutic approaches in nonhuman primates prior to the use of invasive approaches in human clinical trials. Our primate model is intended to: 1) lend greater positive predictive value to human translatable therapies, 2) develop appropriate methods for human translation, 3) lead to basic discoveries that might not be identified in rodent models and are relevant to human translation, and 4) identify new avenues of basic research to "reverse-translate" important questions back to rodent models.

SUBMITTER: Nout YS

PROVIDER: S-EPMC3337011 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury.

Nout Yvette S YS Rosenzweig Ephron S ES Brock John H JH Strand Sarah C SC Moseanko Rod R Hawbecker Stephanie S Zdunowski Sharon S Nielson Jessica L JL Roy Roland R RR Courtine Gregoire G Ferguson Adam R AR Edgerton V Reggie VR Beattie Michael S MS Bresnahan Jacqueline C JC Tuszynski Mark H MH

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20120401 2

Primates are an important and unique animal resource. We have developed a nonhuman primate model of spinal cord injury (SCI) to expand our knowledge of normal primate motor function, to assess the impact of disease and injury on sensory and motor function, and to test candidate therapies before they are applied to human patients. The lesion model consists of a lateral spinal cord hemisection at the C7 spinal level with subsequent examination of behavioral, electrophysiological, and anatomical ou ...[more]

PMID: 22427157

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Project description:BackgroundSpinal cord injury (SCI) is a traumatic disease that is associated with high morbidity, disability, and mortality worldwide. The animal spinal cord contusion model is similar to clinical SCI; therefore, this model is often used to study the pathophysiological changes and treatment strategies for humans after SCI. The present study aimed to introduce a novel, minimally invasive technique to establish an SCI model, and to evaluate its advantages compared with conventional methods.MethodsIncision length, blood loss, length of time, and model success rate during the operation were recorded. Postoperative hematuria, incision hematoma, scoliosis [detected by micro computed tomography (Micro-CT)] and mortality were analyzed to evaluate surgical complications. The visual observation of the tissue was used to compare the effect of laminectomy by 2 methods on the scar hyperplasia at the injured site. Basso-Beattie-Bresnahan (BBB) score and catwalk automated quantitative gait analysis were conducted to measure behavioral function recovery. To evaluate the nerve function recovery of rats postoperatively, somatosensory evoked potential (SEP) and motor evoked potential (MEP) were studied by electrophysiological analyses.ResultsThe results of operation-related parameters of the two models (conventional surgery group vs. minimally invasive surgery group) were as follows: surgical incision length: 23.58±1.58 versus 12.67±1.50 mm (P<0.05), blood loss: 3.96±1.05 versus 1.34±0.87 mL (P<0.05), and total operative time: 12.67±1.78 versus 10.33±1.92 min (P<0.05). In addition, the success rate of the 2 models was 100%. Surgical complications (conventional surgery group vs. minimally invasive surgery group) were as follows: hematuria: 25% versus 8.3%, kyphosis: 25% versus 0%, incision hematoma: 30% versus 9%, and mortality: 25% versus 8.3%. Micro-CT indicated severe scoliosis in the conventional surgery group. Gross tissue results showed that the conventional surgery group had more severe fibrous scar hyperplasia. The results of the BBB scores, catwalk automated quantitative gait analysis, and electrophysiology showed that the difference between the two groups was statistically significant in terms of behavioral recovery and neuroelectrophysiology.ConclusionsThe minimally invasive technique has the advantages of small incision and reduced tissue damage and surgical complications, and may be used as an alternative spinal cord contusion method.

Dataset Information

Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury.

Publications

Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury.

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