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Excessive Calcium Accumulation Impedes Nerve Regeneration- An Experiment in Rats
Kristen A. Hudak, MD; John LoGiudice; Lin Ling Zhang; Agresti Michael; Yu-Hui Yan; Hani Matloub; James Sanger; Ji-Geng Yan
Medical College of Wisconsin, Milwaukee, WI, USA
Introduction: Calcium plays an important role in neuronal function and nerve injury results in excess calcium accumulation. Previous studies have shown the absorption of calcium strongly correlates with functional recovery after nerve injury and that accelerating calcium absorption after injury may improve nerve regeneration. The purpose of this study is to look specifically at improving peripheral nerve regeneration by accelerating calcium absorption.
Materials & Methods: 36 rats were divided into six groups where a crush or sham injury was performed and a micro-osmotic pump was placed around the injured nerve infusing nifedipine, calcitonin, alderonate or saline. After 4 weeks survival time, all animals physiological functional tests including titanic muscle force and EMG as well as histological studies including calcium intensity measurements, nerve fiber counting, mean fiber area size, and calcium accumulated spots (degenerative myelinated nerve fibers) calculation. The calcium intensity was measured at the distal nerve segment by Calcium Green-1 fluorescent stain.
Results: Electrophysiological results correlated with histologic studies. There was an increase in compound motor action potential and tetanic muscle force in the rats treated with nifedipine and calcitonin. The average axon size increased in the crush injured sciatic nerve treated with nifedipine and calcitonin (p=0.013, p=0.004). The immature axon number decreased in rats treated with nifedipine and calcitonin (p=0.097, p=0.005). The number of calcified degenerated myelinated nerve fiber spots decreased in the crush injured rat nerves treated with nifedipine and calcitonin (p=0.009, p=0.008). There was no difference in axon size, axon number or calcified axons in the groups treated with aledronate (p=0.267, p=0.464, p=0.375). When comparing the sham control to the normal control there was a decrease in axon size (p<0.001), increase in immature axon sprout number (p=0.08) and increase in calcified axons (p<0.001) in the sham control group.
Conclusions: This project showed that excessive calcium impeded Schwann cell tube formation and nerve sprout maturation. Our study provided an effective, simple, and reliable method using a micro-osmotic pump with nifedipine or calcitonin at a crushed nerve to accelerate calcium absorption and to improve nerve regeneration. This has the potential to relieve intractable neuralgia and improve functional recovery in patients with nerve injury.
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