Dupuytren's Contracture Recurrence and Treatment Following Collagenase Clostridium Histolyticum Injection: A Longitudinal Assessment in a Veteran Population.

INTRODUCTION: Dupuytren's contracture is a connective tissue disease characterized by an abnormal proliferation of collagen in the palm and fingers, which leads to a decline in hand function because of progressive joint flexion. In addition to surgical and percutaneous interventions, collagenase clostridium histolyticum (CCH, trade name Xiaflex) is an intralesional enzymatic treatment for adults with palpable cords. The objectives of this study are to evaluate factors predictive of recurrence following treatment with CCH and to review the outcomes of repeat treatments with CCH for recurrent contracture. MATERIALS AND METHODS: An institutional review board-approved retrospective chart review was conducted for patients between 2010 and 2017 who received CCH injections for Dupuytren's contracture at a Veterans Affairs hospital. Demographics, comorbidities, affected finger and joint, pre/posttreatment contracture, time to recurrence, and treatment of recurrence were recorded. Successful treatment was defined as contracture ≤5° following CCH, and improvement was defined as ≥20° reduction from baseline contracture. Study cohorts were followed after their secondary treatment, and time to recurrence was recorded and plotted using a Kaplan-Meier curve. A Cox proportional hazards model was used to compare treatment group risk factors for recurrence with a P-value less than .05 defined as statistical significance. RESULTS: Of 174 injections performed for the correction of flexion deformities in 109 patients, 70% (121) were successfully treated with CCH, and an additional 20% (35) had improvement. There was a recurrence of contractures in 43 joints (25%). Of these, 16 contractures were treated with repeat CCH, whereas another 16 underwent limited fasciectomy. In total, 75% (12 of 16) of the repeat CCH group and 75% of the fasciectomy group were successfully treated. Pre-injection contracture of ≥25° was found to be predictive of recurrence (P < .05). CONCLUSIONS: Initial treatment of contracture with CCH had a 70% success rate with 25% recurrence during the study period. Compared with limited fasciectomy, CCH had decreased efficacy. Based on the findings of this study, we believe that the treatment of primary and/or recurrent Dupuytren's contracture with CCH is a safe and less invasive alternative to fasciectomy in the era of telemedicine. CCH treatment requires no suture removal, which allows the ability to assess motion virtually, and the potential consequences of CCH treatment such as skin tears can be assessed and managed conservatively. In the veteran and active duty population, CCH can facilitate faster recovery and return to service. Strengths of this study include a large series of veteran populations with longitudinal follow-up to determine treatment efficacy for primary Dupuytren's contracture and recurrence. Limitations include a smaller sample size compared to previous trials, a lack of standardized follow-up, and the retrospective nature of our study that prohibits randomization to compare outcomes between CCH treatment and fasciectomy efficacy over time. Directions for future research include stratification of patients by joint and specific digit involvement as well as comparison with percutaneous needle fasciotomy, another minimally invasive technique that could benefit the veteran population at increased risk for developing Dupuytren's disease.

Dermal Shift Umbilical Reconstruction: An Innovative and Simple Technique.

SUMMARY: Umbilical reconstruction is a procedure with widespread indications in the setting of congenital or postsurgical loss. Reconstruction of the umbilicus when no remnant of the natural umbilicus is present is also called neoumbilicoplasty. Numerous neoumbilicoplasty techniques have been published, including cartilage grafts, full-thickness skin grafts, and multiflap reconstruction. No consensus has been reached regarding an optimal technique, and many procedures involve complicated designs with small flaps that are difficult to reproduce or explain. The authors divide patients into three types depending on the thickness of the adipose layer of the abdomen. With appropriate patient selection and minor variations depending on patient type, the technique can be applied to all patients. The umbilicus is marked in the appropriate position. Local anesthesia is infiltrated, and the area beneath the skin is defatted. The dermis is then applied to the underlying fascia with a superior shift. The authors describe the technique and its variations and present one illustrative case with additional supplemental digital content. The authors have gone through a progression of techniques to find a simple surgical method yielding consistently reproducible results with minimal complexity, limited morbidity, and an aesthetic final outcome. The authors believe that the technique described here achieves those goals. It can be performed under local anesthetic and with a simple occlusive dressing so that the patient can go on with most of his or her daily activities. There is no scar to suggest a surgical procedure, and patients are extremely happy with the aesthetic outcomes.

Facial Aging: A Quantitative Analysis of Midface Volume Changes over 11 Years.

BACKGROUND: Anatomical studies have identified separate superficial and deep facial fat compartments, leading some to theorize that volume loss from the deep midface causes overlying superficial fat pseudoptosis. Unfortunately, a paucity of evidence exists regarding whether facial fat volume is truly lost with age and, if so, whether it is lost equally or differentially from the superficial and deep compartments. The aim of this study was to quantify volume changes occurring with age within the superficial, deep, and buccal fat compartments of the midface. METHODS: A retrospective longitudinal study was performed evaluating individuals aged 30 to 65 years who underwent facial computed tomography followed by facial computed tomography greater than or equal to 10 years later. Superficial midface, deep midface, and buccal fat volumes were quantified using Horos radiology software. RESULTS: Nineteen subjects met inclusion criteria. Mean total fat volume decreased significantly from 46.47 cc to 40.81 cc (p < 0.01). The mean superficial and deep fat volumes both decreased significantly from 26.10 cc to 23.15 cc (p < 0.01) and from 11.01 cc to 8.98 cc (p < 0.01), respectively. No significant difference was observed in buccal fat volume over time (9.36 cc to 8.68 cc; p = 0.04). Patients lost an average of 11.3 percent of their initial superficial fat volume and 18.4 percent of their initial deep fat volume. CONCLUSIONS: Significant volume loss was observed from both superficial and deep facial fat compartments over a mean 11.3 years. Patients lost a greater percentage of deep facial fat volume, providing support for the theory of pseudoptosis caused by deep midface fat loss.

Anconeus Epitrochlearis Muscle Associated With Cubital Tunnel Syndrome: A Case Series.

Background: Cubital tunnel syndrome is a common compressive neuropathy of the upper extremity. The anconeus epitrochlearis muscle is an unusual but occasional contributor. We review our experience with this anomalous muscle in elbows with cubital tunnel syndrome. Methods: We retrospectively reviewed charts of 13 patients noted to have an anconeus epitrochlearis muscle associated with cubital tunnel syndrome. Results: Ten patients had unilateral ulnar neuropathy supported by nerve conduction studies. Three had bilateral cubital tunnel syndrome symptoms with 1 of those having normal nerve conduction studies for both elbows. Eight elbows were treated with myotomy of the anconeus epitrochlearis muscle and submuscular transposition of the ulnar nerve. The other 8 elbows were treated with myotomy of the anconeus epitrochlearis muscle and in situ decompression of the ulnar nerve only. All but 1 patient had either clinical resolution or improvement of symptoms at follow-up ranging from 2 weeks to 1 year after surgery. The 1 patient who had persistent symptoms had received myotomy and in situ decompression of the ulnar nerve only. Conclusions: An anomalous anconeus epitrochlearis occasionally results in compression of the ulnar nerve but is usually an incidental finding. Its contribution to compression neuropathy can be tested intraoperatively by passively ranging the elbow while observing the change in vector and tension of its muscle fibers over the ulnar nerve. Regardless of findings, we recommend myotomy of the muscle and in situ decompression of the ulnar nerve. Submuscular transposition of the ulnar nerve may be necessary if there is subluxation.

A Novel Surgical Technique for Resuspension of Digital Pulp Tissue after Degloving Injuries.

Adherence of pulp tissue to the underlying distal phalanx is required for fundamental actions including grip, proprioception, and fine motor skills. Disruption of the fibrous septa causes sliding between the distal phalanx and overlying soft tissues, hindering basic hand function. The authors present a novel surgical technique in which the fibrous pulp septa are resuspended to the distal phalanx with bone anchors and sclerosing agents after a closed degloving injury.

Increasing Calcium Level Limits Schwann Cell Numbers In Vitro following Peripheral Nerve Injury.

Background After peripheral nerve injury, there is an increase in calcium concentration in the injured nerves. Our previous publications have shown that increase in calcium concentration correlated well with degree of nerve injury and that local infusion of calcitonin has a beneficial effect on nerve recovery. Schwann cells play a pivotal role in regeneration and recovery. We aim to examine cultured Schwann cell survivals in various concentrations of calcium-containing growth media and the effect of calcitonin in such media. Methods To establish baseline in postinjury state, crush injury was induced in male Sprague-Dawley rats' sciatic nerves. Extra- and intraneural calcium concentrations were measured. To study Schwann cell survival, uninjured sciatic nerve segment was harvested and cultured in media containing various amounts of calcium. To study the effect of calcitonin, nerve harvest and culture were done in four additional media: (1) normal control, (2) normal control with calcitonin, (3) high calcium medium, and (4) high calcium medium with calcitonin. Schwann cells were studied and analyzed under fluorescent conditions. Results With increasing calcium concentration, there was a significant decrease in the number of Schwann cells. For the experimental groups, in which calcitonin had been added to the growth medium, there were similar amounts of Schwann cells present in both high and low calcium-containing medium. Conclusion Schwann cells are sensitive to increasing calcium concentration. Calcitonin counteracts the detrimental effects of high calcium on Schwann cell survival. This can have significant future clinical implications for patients with peripheral nerve injuries.

Best time window for the use of calcium-modulating agents to improve functional recovery in injured peripheral nerves-An experiment in rats.

Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc.

Effect of calcitonin on cultured schwann cells.

INTRODUCTION: After nerve injury, calcium concentrations in intranerve fibers quickly increase. We have shown that functional recovery of injured nerves correlates with calcium absorption. A slight increase in calcium reduces the number of Schwann cells present. Calcitonin therapy greatly improves regeneration by accelerating calcium absorption. We examined the effect of adding calcitonin to higher concentration calcium media on cultured Schwann cells. METHODS: The cells, isolated from intact sciatic nerves, were cultured with normal or higher concentration calcium media with or without calcitonin. Schwann cells were incubated with anti-S-100, goat-anti-mouse, and propidium iodide and then viewed through fluorescent light and phase-contrast microscopy for observation and analysis. RESULTS: The cells in each calcitonin-containing medium showed many Schwann cells, however, the cells in the higher concentration calcium media showed fewer and more defective Schwann cells. CONCLUSION: These results show that calcitonin protects against the harmful effects of excessive calcium encountered in peripheral nerve injury. Muscle Nerve 56: 768-772, 2017.

Hyoid Suspension Neck Lift.

BACKGROUND: The shape of the deep cervical structures is the shape of an aesthetic neck. With age, changes can obstruct visualization of that shape. Achieving a youthful contour requires removal of excess skin and fat but also control of the platysma to allow skin to redrape like a blanket over an underlying framework. The authors' technique makes the platysma part of the deep cervical structures whose shape underlies an attractive neck and allows the skin to redrape to that contour. METHODS: To make the platysma conform closely to the deep cervical structures and allow the skin to show that new form, the authors developed a procedure that includes removal of excess fat, attaching the platysma to the hyoid fascia, approximating the edges of the platysma above and below that suture, and wide undermining of skin to allow it to re-drape naturally over those deeper structures. RESULTS: Over 7 years, 110 patients underwent aesthetic facial surgery that included hyoid suspension of the platysma. One patient had recurrence of platysmal bands after failure of the key suture. Complications included hematoma in three patients and submental seromas in three patients, but no permanent nerve injury, no skin loss from vascular compromise, no reported changes in vocal resonance, and no complaints of difficulty swallowing. CONCLUSIONS: This method allows the skin to redrape over a youthful framework and produces reliable aesthetic and long lasting results. It is a simple, reproducible, teachable technique that enables surgeons to achieve results previously difficult to obtain in a single operation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic).

BACKGROUND: Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. METHODS: A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. RESULTS: Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. CONCLUSIONS: The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning.

Neural systemic impairment from whole-body vibration.

Insidious brain microinjury from motor vehicle-induced whole-body vibration (WBV) has not yet been investigated. For a long time we have believed that WBV would cause cumulative brain microinjury and impair cerebral function, which suggests an important risk factor for motor vehicle accidents and secondary cerebral vascular diseases. Fifty-six Sprague-Dawley rats were divided into seven groups (n = 8): 1) 2-week normal control group, 2) 2-week sham control group (restrained in the tube without vibration), 3) 2-week vibration group (exposed to whole-body vibration at 30 Hz and 0.5g acceleration for 4 hr/day, 5 days/week, for 2 weeks), 4) 4-week sham control group, 5) 4-week vibration group, 6) 8-week sham control group, and 7) 8-week vibration group. At the end point, all rats were evaluated in behavior, physiological, and brain histopathological studies. The cerebral injury from WBV is a cumulative process starting with vasospasm squeezing of the endothelial cells, followed by constriction of the cerebral arteries. After the 4-week vibration, brain neuron apoptosis started. After the 8-week vibration, vacuoles increased further in the brain arteries. Brain capillary walls thickened, mean neuron size was obviously reduced, neuron necrosis became prominent, and wide-ranging chronic cerebral edema was seen. These pathological findings are strongly correlated with neural functional impairments.

Spindle Cell Lipoma of the Neck: Review of the Literature and Case Report.

Spindle cell lipomas (SCL) are benign, slow growing tumors arising most frequently in the subcutaneous tissue of the upper back, posterior neck, and shoulders in males aged 40-70 years. Local excision is generally curative. Classification of lipomatous tumors has progressed recently, and tumors of similar morphology and unusual presentation are increasingly reported, thereby making correct diagnosis even more vital. SCL require pathologic differentiation from liposarcoma, other spindle cell neoplasms, and myxoid lesions for treatment purposes. Cytology, histology, and cytogenetics, in conjunction with clinical presentation, are paramount in arriving at the correct diagnosis of spindle cell lipoma. We present a case report with characteristics typical of an SCL along with a literature review to further elucidate the diagnosis and surgical treatment of this soft tissue tumor.

Calcitonin pump improves nerve regeneration after transection injury and repair.

INTRODUCTION: After nerve injury, excessive calcium impedes nerve regeneration. We previously showed that calcitonin improved nerve regeneration in crush injury. We aimed to validate the direct effect of calcitonin on transected and repaired nerve. METHODS: Two rat groups (n = 8) underwent sciatic nerve transection followed by direct repair. In the calcitonin group, a calcitonin-filled mini-osmotic pump was implanted subcutaneously, with a catheter parallel to the repaired nerve. The control group underwent repair only, without a pump. Evaluation and comparison between the groups included: (1) compound muscle action potential recording of the extensor digitorum longus (EDL) muscle; (2) tetanic muscle force test of EDL; (3) nerve calcium concentration; and (4) nerve fiber count and calcified spot count. RESULTS: The calcitonin pump group showed superior recovery. CONCLUSIONS: Calcitonin affects injured and repaired peripheral nerve directly. The calcitonin-filled mini-osmotic pump improved nerve functional recovery by accelerating calcium absorption from the repaired nerve. This finding has potential clinical applications.

Detergent-free Decellularized Nerve Grafts for Long-gap Peripheral Nerve Reconstruction.

BACKGROUND: Long-gap peripheral nerve defects arising from tumor, trauma, or birth-related injuries requiring nerve reconstruction are currently treated using nerve autografts and nerve allografts. Autografts are associated with limited supply and donor-site morbidity. Allografts require administration of transient immunosuppressants, which has substantial associated risks. To overcome these limitations, we investigated the use of detergent-free decellularized nerve grafts to reconstruct long-gap nerve defects in a rodent model and compared it with existing detergent processing techniques. METHODS: Nerve grafts were harvested from the sciatic nerves of 9 donor rats. Twenty-four recipient rats were divided into 4 groups (6 animals per group): (1) nerve grafts (NG, positive control), (2) detergent-free decellularized (DFD) grafts, (3) detergent decellularized grafts, and (4) silicone tube conduits (negative control). Each recipient rat had a 3.5-cm graft or conduit sutured across a sciatic nerve transection injury. All animals were harvested at 12 weeks postimplantation for functional muscle analysis and nerve histomorphometry. RESULTS: Histomorphometry results indicated maximum growth in NG when compared with other groups. DFD and detergent decellularized groups showed comparable regeneration at 12 weeks. Silicone tube group showed no regeneration as expected. Muscle force data indicated functional recovery in NG and DFD groups only. CONCLUSIONS: This study describes a detergent-free nerve decellularization technique for reconstruction of long-gap nerve injuries. We compared DFD grafts with an established detergent processing technique and found that DFD nerve grafts are successful in promoting regeneration across long-gap peripheral nerve defects as an alternative to existing strategies.

A quantitative study of vibration injury to peripheral nerves-introducing a new longitudinal section analysis.

PURPOSE: Long-term vibrations are known to cause neurovascular diseases, which are common in workers who operate handheld power tools or motor vehicles. Understanding the neuropathology of vibration-induced nerve injury is critical to its prevention and treatment. This study aims to evaluate whether light microscopy of longitudinal nerve sections can be used as a simple yet effective method for quantifying nerve injury. METHODS: The rats were split into two groups that were subjected to vibration (4 h/day) for 7 or 14 days. They were then allowed to rest for varying periods of time. Longitudinal sections of the tail nerves were examined under light microscopy. Injuries to the nerves were classified into three types, counted, tallied, and then divided by the length of the nerve being studied. RESULTS: Both 7 and 14 days of vibration showed significant damage when no recovery time was given. After 1 month of rest, the 7-day group began to show signs of recovery, but the 14-day group did not. After 2 months of rest, the 7-day vibration group showed almost complete recovery, while the 14-day vibration group still showed significant damage when compared to the sham control groups. CONCLUSION: The amount of damage to the myelin sheath directly correlated with vibration duration. When vibrated for longer than 7 days, nerve recovery was limited. This study also demonstrated that light microscopy of longitudinal slices is a simple yet effective method of quantifying the nerve damage.

Early evaluation of nerve regeneration after nerve injury and repair using functional connectivity MRI.

Resting state functional connectivity magnetic resonance imaging studies in rat brain show brain reorganization caused by nerve injury and repair. In this study, distinguishable differences were found in healthy, nerve transection without repair (R-) and nerve transection with repair (R+) groups in the subacute stage (2 weeks after initial injury). Only forepaw on the healthy side was used to determine seed voxel regions in this study. Disturbance of neuronal network in the primary sensory region of cortex occurs within two hours after initial injury, and the network pattern was restored in R+ group in subacute stage, while the disturbed pattern remained in R- group. These are the central findings of the study. This technique provides a novel way of detecting and monitoring the effectiveness of peripheral nerve injury treatment in the early stage and potentially offers a tool for clinicians to avoid poor clinical outcomes.

C7 nerve root sensory distribution in peripheral nerves: a bold functional magnetic resonance imaging investigation at 9.4 T.

INTRODUCTION: In this study we used a rat model to elucidate the linear make-up of each major nerve of the upper limb by the C7 root through sensory stimulation and functional magnetic resonance imaging (fMRI). METHODS: The C7 nerve root and major nerves of the right forelimb were stimulated electrically. Blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) was performed concurrently. Voxel overlap within the primary sensory cortex was calculated. RESULTS: C7 comprised sensation in <1% in the musculocutaneous nerve, 6% in the ulnar nerve, 16% in the radial nerve, and 19% in the median nerve (P<0.005 for each). The overlap was always <25% for each major nerve. CONCLUSIONS: This study helps explain why C7 is a suitable donor for brachial plexus injury treatment and why there is only a transient sensory deficit after transfer.

A new computerized morphometric analysis for peripheral nerve study.

The commonly used methods to quantify axon numbers and mean area include manual and semiautomated procedures. The authors introduce a new fully automated method of morphometric analysis using ImageJ and Paint.net software to improve efficiency and accuracy. A total of six rat sciatic nerves were examined for their axon numbers and mean axon area by comparing the manual method or semiautomated MetaVue method with the new ImageJ method. It was observed that the number of axons for manual counting and ImageJ were 4,630 ± 403 and 4,779 ± 352, respectively, and the difference was not statistically significant (p > 0.5, t-test). The mean axon area measured was 13.44 ± 2.62 µm2 for MetaVue and 8.87 ± 0.78 µm2 for ImageJ, respectively, and the difference was statistically significant (p < 0.01, t-test). The standard error and coefficient of variation of MetaVue were 1.07 and 0.195; and for ImageJ were 0.32 and 0.087. The authors conclude that their new approach demonstrates improved convenience, time efficiency, accuracy, and less operator error or bias.

A rat model for long-gap peripheral nerve reconstruction.

BACKGROUND: The rat model has had limited utility for the study of long nerve gaps because of the small size of the animal. The authors sought to develop a simple, effective rat model for reconstruction of long nerve gap defects. METHODS: Fifteen rats had a sciatic nerve transection followed by reconstruction. Positive control rats received a 1-cm isograft. Negative control rats received a 3.5-cm hollow silicone conduit, and experimental rats received a 4-cm isograft; these were implanted in a looped configuration to accommodate the long length. Nerves were harvested at 6 weeks (1-cm grafts) and 12 weeks (3.5-cm conduits and 4-cm grafts) for histologic and histomorphometric evaluation. RESULTS: The 1-cm and 4-cm isograft groups showed robust regeneration in the distal nerve segment. The 3.5-cm hollow conduits showed absolutely no initiation of nerve regeneration. Histomorphometric values were as expected for the specified gap length. CONCLUSIONS: This study describes a simple and effective long nerve gap rat model for experiments on nerve grafts and nerve conduits. The long nerve graft model can be useful for studying techniques such as processed nerve grafts, which are currently a topic of frequent investigation. The 3.5-cm hollow conduit "no-regrowth" long-gap model is ideal for investigating conduit-based tissue-engineering solutions for long-gap nerve repair. The authors' approach overcomes the size limitation of the small animal while exploiting the features that make the rat the model of choice for preliminary nerve studies.

The effect of calcium modulating agents on peripheral nerve recovery after crush.

After a nerve injury, calcium concentration in the intra-nerve fiber drastically increases. The purpose of our study was to test an implantable micro-osmotic pump to deliver medications to accelerate calcium absorption, thereby greatly improving nerve regeneration. Twenty-four SD rats were divided into four groups of six each: (1) Sham control: crush injury to sciatic nerve only; (2) Crush injury with a Nifedipine pump; (3) Crush injury with a Calcitonin pump; (4) Crush injury with a Saline pump. Each rat's right sciatic nerve was crushed. The micro-osmotic pump was implanted in the neck, and the dripping tube was routed to the injured nerve. After four weeks of survival time, compound muscle action potential (CMAP), tetanic muscle force (TMF), myelinated nerve fiber area (NFA), nerve calcium concentration (NCC), and calcified spots (CS) were evaluated. The calcium absorption rate (CAR) was also determined. The order from highest to lowest recovery rate was Nifedipine>Calcitonin>Sham control>Saline. Differences among the groups were statistically significant (P<0.001, ANOVA test), and the difference between Nifedipine/Calcitonin and Saline/Sham control were all statistically significant (P<0.001, t-test). The correlation rate of NCC with CMAP/TMF and with NFA/CS and CAR were calculated to be 0.99 (all P<0.001, Pearson's Correlation). We conclude from this study that nerve regeneration strongly correlated with calcium absorption; our new data has shown greatly improved nerve functional recovery, and this can potentially be translated into clinical applications.