American Society for Peripheral Nerve

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Accelerating Calcium Absorption Significantly Improves Peripheral Nerve Regeneration – an Experiment in Rats
Ziyi Wang; Ji-Geng Yan; James Sanger; Lin-Ling Zhang; Yu-Hui Yan, MD; Micheal Agresti; Hani S. Matloub
Medical College of Wisconsin, Milwaukee, WI, USA

Background: After nerve injury, the Ca2+-ATPase and Na/Ca2+ transporter are damaged. Calcium concentration of the intra-nerve fiber drastically increases and causes axon degeneration.

Purpose: The purpose of our study is to test a novel approach of implanting a micro-osmotic pump to deliver medicine to accelerate calcium absorption, thereby greatly improving nerve regeneration.

Methods: Thirty SD rats were divided into five groups of six each: 1) Sham Control; 2) Pump with Nifedipine; 3) Pump with Calcitonin; 4) Pump with Alendronate; and 5) Pump with Saline. Each rat's right sciatic nerve was crushed with a needle holder to produce 30 pound force, in order to rupture all nerve fibers. The micro-osmotic pump was implanted dorsal of the neck, and the dripping tube is routed towards the injured sciatic nerve to consistently deliver the medicines. The Sham control group was crushed but not treated. After four weeks of survival time, the electrophysiological study of compound muscle action potential (CMAP), tetanic muscle force (TMF), nerve fiber diameter (NF), and calcium intensity in relative fluorescent units (RFU) were evaluated and compared among the five groups.

Results: The Recovery Rate for each test was determined by the value on the treatment side (right) divided by the value on the normal side (left). The Calcium Absorption Rate was determined by the average RFU of treatment divided by the average RFU of Sham Control, and subtracted from 100%. As shown in Figure 1, results of the micro-osmotic pumps with calcium absorbing medicines were greatly superior to that of Saline or Sham Control. The order from highest to lowest recovery rate was Nifedipine > Calcitonin > Alendronate > Sham Control > Saline. The differences among the groups were statistically significant (P < 0.001, ANOVA Test), and the difference between Nifedipine or Calcitonin and Saline or Sham control was statistically significant (P < 0.001, paired T-Test). The correlation between CMAP and Calcium Absorption Rate was calculated to be 0.96 (P < 0.05, Pearson's Correlation).

Conclusion:
1. Calcium absorption rate strongly correlates with nerve functional recovery rate.
2. Our novel approach using micro-osmotic pump to deliver calcium absorption medications has shown greatly improved nerve functional recovery, and this can potentially be translated into clinical implications.



Figure 1. Electrophysiological Recovery and Calcium Absorption Rate.
CMAP = Compound Muscle Action Potential, TMF = Tetanic Muscle Force
Calcium Absorption Rate = [1 – (Average RFU of Treatment / Average RFU of Sham Control)] * 100%


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