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The course of recovery of locomotor function over a 10-week observation period in a rat model of femoral nerve resection and autograft repair.

ABSTRACT: BACKGROUND:A great extent of knowledge on peripheral nerve regeneration has been gathered using the rat sciatic nerve model. The femoral nerve model of the rat offers an interesting alternative, as it lacks disadvantageous features such as automutilation. For the analysis of locomotor behavior in rats after sciatic nerve injury, the CatWalk™ XT Gait Analysis System is often used. However, lesions of the femoral nerve in the rat have yet remained unstudied with this method. MATERIAL AND METHODS:Ten male Sprague Dawley rats were evaluated with the CatWalk XT to study their gait after a 6-mm resection of the right femoral nerve and reconstruction with an autologous nerve graft. Animals were observed for 10 weeks after surgery. RESULTS:Print Area, Print Length, Swing Speed, and Duty Cycle decreased to a minimum of 40% of baseline 2 weeks after surgery. Swing Time was elevated more than twofold at this time point. However, all these parameters recovered back to >90% of baseline values at 10 weeks after surgery. This degree of functional recovery has not been reported after sciatic nerve resection and autograft repair. Base of support varied minimally postoperatively in contrast to a strong decrement after sciatic nerve resection and repair. CONCLUSION:We hereby provide a comprehensive in-depth analysis of how to study functional recovery after injury of the femoral nerve in the rat via the CatWalk XT. We place special emphasis on highlighting the differences between the femoral nerve and sciatic nerve injury model in this context.

SUBMITTER: Heinzel JC

PROVIDER: S-EPMC7177579 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The course of recovery of locomotor function over a 10-week observation period in a rat model of femoral nerve resection and autograft repair.

Heinzel Johannes Christoph JC Hercher David D Redl Heinz H

Brain and behavior 20200225 4

<h4>Background</h4>A great extent of knowledge on peripheral nerve regeneration has been gathered using the rat sciatic nerve model. The femoral nerve model of the rat offers an interesting alternative, as it lacks disadvantageous features such as automutilation. For the analysis of locomotor behavior in rats after sciatic nerve injury, the CatWalk<sup>™</sup> XT Gait Analysis System is often used. However, lesions of the femoral nerve in the rat have yet remained unstudied with this method.<h4> ...[more]

PMID: 32097542

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Project description:Computerized gait analysis is a common evaluation method in rat models of hind limb nerve injuries, but its use remains unpublished in models of segmental nerve injury of the forelimb. It was the aim of this work to investigate if computerized gait analysis is a feasible evaluation method in a rat model of segmental median nerve injury and autograft repair. Ten male Lewis rats underwent 7-mm resection of the right median nerve with immediate autograft repair. The left median nerve was resected without repair and served as an internal control. Animals were assessed for 12 weeks after surgery via CatWalk (CW) gait analysis every 2 weeks. Evaluation of motor recovery by means of the grasping test was performed weekly while electrophysiological measurements were performed at the end of the observation period. CW data were correlated with grasping strength at each post-operative time point. CW data were also correlated with electrophysiology using linear regression analysis. Principal component analysis was performed to identify clusters of outcome metrics. Recovery of motor function was observable 4 weeks after surgery, but grasping strength was significantly reduced (p < 0.01) compared to baseline values until post-operative week 6. In terms of sensory recovery, the pain-related parameter Duty Cycle showed significant (p < 0.05) recovery starting from post-operative week 8. The Print Area of the right paw was significantly (p < 0.05) increased compared to the left side starting from post-operative week 10. Various parameters of gait correlated significantly (p < 0.05) with mean and maximum grasping strength. However, only Stand Index showed a significant correlation with compound muscle action potential (CMAP) amplitude (p < 0.05). With this work, we prove that computerized gait analysis is a valid and feasible method to evaluate functional recovery after autograft repair of the rat median nerve. We were able to identify parameters such as Print Area, Duty Cycle, and Stand Index, which allow assessment of nerve regeneration. The course of these parameters following nerve resection without repair was also assessed. Additionally, external paw rotation was identified as a valid parameter to evaluate motor reinnervation. In summary, computerized gait analysis is a valuable additional tool to study nerve regeneration in rats with median nerve injury.

Project description:BackgroundPeripheral nerve stimulation with implanted nerve cuff electrodes can restore standing, stepping and other functions to individuals with spinal cord injury (SCI). We performed the first study to evaluate the clinical electrodiagnostic changes due to electrode implantation acutely, chronic presence on the nerve peri- and post-operatively, and long-term delivery of electrical stimulation.MethodsA man with bilateral lower extremity paralysis secondary to cervical SCI sustained 5 years prior to enrollment received an implanted standing neuroprosthesis including composite flat interface nerve electrodes (C-FINEs) electrodes implanted around the proximal femoral nerves near the inguinal ligaments. Electromyography quantified neurophysiology preoperatively, intraoperatively, and through 1 year postoperatively. Stimulation charge thresholds, evoked knee extension moments, and weight distribution during standing quantified neuroprosthesis function over the same interval.ResultsFemoral compound motor unit action potentials increased 31% in amplitude and 34% in area while evoked knee extension moments increased significantly (p < 0.01) by 79% over 1 year of rehabilitation with standing and quadriceps exercises. Charge thresholds were low and stable, averaging 19.7 nC ± 6.2 (SEM). Changes in saphenous nerve action potentials and needle electromyography suggested minor nerve irritation perioperatively.ConclusionsThis is the first human trial reporting acute and chronic neurophysiologic changes due to application of and stimulation through nerve cuff electrodes. Electrodiagnostics indicated preserved nerve health with strengthened responses following stimulated exercise. Temporary electrodiagnostic changes suggest minor nerve irritation only intra- and peri-operatively, not continuing chronically nor impacting function. These outcomes follow implantation of a neuroprosthesis enabling standing and demonstrate the ability to safely implant electrodes on the proximal femoral nerve close to the inguinal ligament. We demonstrate the electrodiagnostic findings that can be expected from implanting nerve cuff electrodes and their time-course for resolution, potentially applicable to prostheses modulating other peripheral nerves and functions.Trial registrationClinicalTrials.gov NCT01923662 , retrospectively registered August 15, 2013.

Project description:Background and objectives: Bisphosphonates represent selective inhibitors of excess osteoblastic bone resorption that characterizes all osteopathies, targeting osteoclasts and their precursors. Their long-term administration in postmenopausal women suffering from osteoporosis has resulted in neural adverse effects. The current study focuses on the research of possible alterations in the femoral nerve, caused by bisphosphonates. We hypothesized that bisphosphonates, taken orally (per os), may produce degenerative changes to the femoral nerve, affecting lower-limb posture and walking neuronal commands. Materials and Methods: In order to support our hypothesis, femoral nerve specimens were extracted from ten female 12-month-old Wistar rats given 0.05 milligrams (mg) per kilogram (kg) of body weight (b.w.) per week alendronate per os for 13 weeks and from ten female 12-month-old Wistar rats given normal saline that were used as a control group. Specimens were studied using immunohistochemistry for selected antibodies NeuN (Neuronal Nuclear Protein), a protein located within mature, postmitotic neural nucleus, and cytosol and Sox10 (Sex-determining Region Y (SRY) - High-Motility Group (HMG) - box 10). The latter marker is fundamental for myelination of peripheral nerves. Obtained slides were examined under a light microscope. Results: Samples extracted from rats given alendronate were more Sox10 positive compared to samples of the control group, where the marker's expression was not so intense. Both groups were equally NeuN positive. Our results are in agreement with previous studies conducted under a transmission electron microscope. Conclusions: The suggested pathophysiological mechanism linked to histological alterations described above is possibly related to toxic drug effects on Schwann and neuronal cells. Our hypothesis enhances the existing scientific evidence of degenerative changes present on femoral nerve following bisphosphonates administration, indicating a possible relationship between alendronate use and neuronal function.

Dataset Information

The course of recovery of locomotor function over a 10-week observation period in a rat model of femoral nerve resection and autograft repair.

Publications

The course of recovery of locomotor function over a 10-week observation period in a rat model of femoral nerve resection and autograft repair.

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