Guiding Device for Precision Grafting of Peripheral Nerves in Complete Thoracic Spinal Cord Injury: Design and Sizing for Clinical Trial.

BACKGROUND: In an effort to translate preclinical success in achieving spinal cord regeneration through peripheral nerve grafts, this study details the design and sizing of a guiding device for precision grafting of peripheral nerves for use in a clinical trial in complete (AIS-A) thoracic spinal cord injury (SCI). The device's design and sizing are compared to a simulation of human spinal cord sizes based on the best available data. METHODS: Spinal cord segmental sizes were generated by computer simulation based on data from a meta-analysis recently published by our group. Thoracic segments T2-T12 were plotted, and seven elliptical shapes were positioned across the center of the distribution of sizes. Geometrical measures of error-of-fit were calculated. CAD modeling was used to create cranial and caudal interfaces for the human spinal cord, aiming to guide descending white matter tracts to gray matter at the caudal end of the device and ascending white matter tracts to gray matter at the cranial end of the device. The interfaces were compared qualitatively to the simulated spinal cord sizes and gray-to-white matter delineations. RESULTS: The mean error-of-fit comparing simulated spinal cord segments T2-T12 to the best elliptical shape was 0.41 and 0.36 mm, and the 95th percentile was found at 1.3 and 0.98 mm for transverse and anteroposterior diameter, respectively. A guiding device design was reached for capturing the majority of corticospinal axons at the cranial end of the device and guiding them obliquely to gray matter at the caudal end of the device. Based on qualitative comparison, the vast majority of spinal cord sizes generated indicate an excellent fit to the device's interfaces. CONCLUSION: A set of SCI guiding devices of seven sizes can cover the variability of human thoracic spinal cord segments T2-T12 with an acceptable error-of-fit for the elliptical shape as well as guiding channels. The computational framework developed can be used with other medical technologies involving the human spinal cord where exact sizes and positioning are of importance.

A Review of the Segmental Diameter of the Healthy Human Spinal Cord.

Knowledge of the average size and variability of the human spinal cord can be of importance when treating pathological conditions in the spinal cord. Data on healthy human spinal cord morphometrics have been published for more than a century using different techniques of measurements, but unfortunately, comparison of results from different studies is difficult because of the different anatomical landmarks used as reference points along the craniocaudal axis for the measurements. The aim of this review was to compute population estimates of the transverse and anteroposterior diameter of the human spinal cord by comparing and combining previously published data on a normalized craniocaudal axis. We included 11 studies presenting measurements of spinal cord cross-sectional diameters, with a combined sample size ranging from 15 to 488 subjects, depending on spinal cord level. Based on five published studies presenting data on the lengths of the segments of the spinal cord and vertebral column, we calculated the relative positions of all spinal cord neuronal segments and vertebral bony segments and mapped measurements of spinal cord size to a normalized craniocaudal axis. This mapping resulted in better alignment between studies and allowed the calculation of weighted averages and standard deviations (SDs) along the spinal cord. These weighted averages were smoothed using a generalized additive model to yield continuous population estimates for transverse and anteroposterior diameter and associated SDs. The spinal cord had the largest transverse diameter at spinal cord neuronal segment C5 (13.3 ± 2.2), decreased to segment T8 (8.3 ± 2.1), and increased slightly again to 9.4 ± 1.5 at L3. The anteroposterior diameter showed less variation in size along the spinal cord at C5 (7.4 ± 1.6), T8 (6.3 ± 2.0), and L3 (7.5 ± 1.6). All estimates are presented in millimeters ± 2 SDs. We conclude that segmental transverse and anteroposterior diameters of the healthy human spinal cord from different published sources can be combined on a normalized craniocaudal axis and yield meaningful population estimates. These estimates could be useful in routine management of patients with neurodegenerative diseases as well as for clinical research and experimental applications aimed at surgical spinal cord repair.

Recovery of laryngeal function after intraoperative injury to the recurrent laryngeal nerve.

Loss of function in the recurrent laryngeal nerve (RLN) during thyroid/parathyroid surgery, despite a macroscopically intact nerve, is a challenge which highlights the sensitivity and complexity of laryngeal innervation. Furthermore, the uncertain prognosis stresses a lack of capability to diagnose the reason behind the impaired function. There is a great deal of literature considering risk factors, surgical technique and mechanisms outside the nerve affecting the incidence of RLN paresis during surgery. To be able to prognosticate recovery in cases of laryngeal dysfunction and voice changes after thyroid surgery, the surgeon would first need to define the presence, location, and type of laryngeal nerve injury. There is little data describing the events within the nerve and the neurobiological reasons for the impaired function related to potential recovery and prognosis. In addition, very little data has been presented in order to clarify any differences between the transient and permanent injury of the RLN. This review aims, from an anatomical and neurobiological perspective, to provide an update on the current understandings of surgically-induced injury to the laryngeal nerves.

Modeling of testosterone regulation by pulse-modulated feedback.

The continuous part of a hybrid (pulse-modulated) model of testosterone (Te) feedback regulation in the human male is extended with infinite-dimensional and nonlinear blocks, to obtain the dynamics that better agree with the hormone concentration profiles observed in clinical data. A linear least-squares based optimization algorithm is developed for the purpose of detecting impulses of gonadotropin-releasing hormone (GnRH) from measured concentration of luteinizing hormone (LH). The estimated impulse parameters are instrumental in evaluating the frequency and amplitude modulation functions parameterizing the pulse-modulated feedback. The proposed approach allows for the identification of all model parameters from the hormone concentrations of Te and LH. Simulation results of the complete estimated closed-loop system exhibiting similar to the clinical data behavior are provided.

Bone loss around a stable, partly threaded hydroxyapatite-coated cup: a prospective cohort study using RSA and DXA.

STUDY PURPOSE: Aseptic loosening of the acetabular component is the most common reason for revision after primary THA, and periprosthetic demineralisation has been described as a potential cause for this process. The trabeculae-oriented pattern (TOP)-cup is a flat, hydroxyapatite (HA)-coated titanium shell with a threaded rim that was developed in order to minimise periprosthetic bone loss. We hypothesised that this cup provides good primary stability and improves preservation of periprosthetic bone mineral density (BMD). BASIC PROCEDURES: A prospective cohort study on 30 patients receiving the TOP cup was carried out. Preoperative total hip BMD and postoperative periprosthetic BMD in five periprosthetic regions of interest were investigated by dual energy radiographic absorptiometry (DXA), cup migration was analysed by radiostereometry (RSA), and the Harris hips score (HHS) was determined. MAIN FINDINGS: Mean HHS increased from 49 (24-79) preoperatively to 99 (92-100) after two years. DXA after one year demonstrated substantial BMD loss in the proximal periprosthetic zones 1 (-18%), zone 2 (-16 %) and zone 3 (-9%, all p<0.001 when compared with baseline BMD determined immediately postoperatively). The bone loss in these regions did not recover after two years. RSA (performed on 16 patients) showed that only very limited micromotion of the implant occurred: Mean cranial migration was 0.01 mm (95% confidence interval (CI): -0.09-0.12) and mean inclination decreased by 0.02º (CI: -0.43-0.39) after two years. CONCLUSION: We conclude that the TOP cup provides good primary stability in the short-term. However, substantial BMD loss in proximal periprosthetic areas indicates that the design of this cup cannot prevent periprosthetic bone loss that has also been observed around other uncemented cups.

Effects of postoperative weight-bearing on body composition and bone mineral density after uncemented total hip arthroplasty.

OBJECTIVE: To investigate whether a postoperative weight-bearing regimen affects changes in bone mineral density and body composition after uncemented total hip arthroplasty, and to investigate the changes over a 5-year period after the surgical procedure. DESIGN: Secondary analysis of a previous randomized controlled trial. METHODS: A total of 39 patients were randomized to immediate full weight-bearing or partial weight-bearing for 3 months. Dual-energy X-ray absorptiometry was used to measure bone mineral density of the contralateral hip and both heels and to measure body composition. RESULTS: The weight-bearing regimen had no effect on change in bone mineral density or body composition after 3 and 12 months. At 5 years, there was a decrease in bone mineral density of 3% in the total body and 2-3% in the contralateral hip regions. At 5 years we found a decrease in total body bone mineral content of 5%, but no changes in fat mass or lean mass compared with preoperative values. CONCLUSION: The postoperative weight-bearing regimen had no effect on changes in body composition or bone mineral density. Five years after total hip arthroplasty there was a decrease in bone mineral content and bone mineral density, but no changes in lean mass or fat mass.

A prospective cohort study on the short collum femoris-preserving (CFP) stem using RSA and DXA. Primary stability but no prevention of proximal bone loss in 27 patients followed for 2 years.

BACKGROUND AND PURPOSE: Short femoral stems have been introduced in total hip arthroplasty in order to save proximal bone stock. We hypothesized that a short stem preserves periprosthetic bone mineral density (BMD) and provides good primary stability. METHODS: We carried out a prospective cohort study of 30 patients receiving the collum femoris-preserving (CFP) stem. Preoperative total hip BMD and postoperative periprosthetic BMD in Gruen zones 1-7 were investigated by dual-energy x-ray absorptiometry (DXA), stem migration was analyzed by radiostereometric analysis (RSA), and the Harris hip score (HHS) was determined. RESULTS: 2 patients were excluded intraoperatively and 1 patient was revised due to a deep infection, leaving 27 patients for analysis. The mean HHS increased from 49 (24-79) preoperatively to 99 (92-100) after 2 years. DXA after 1 year showed substantial loss of BMD in Gruen zone 7 (-31%), zone 6 (-19%), and zone 2 (-13%, p < 0.001) compared to baseline BMD determined immediately postoperatively. The bone loss in these regions did not recover after 2 years, whereas the more moderate bone loss in Gruen zones 1, 3, and 5 partially recovered. There was a correlation between low preoperative total hip BMD and a higher amount of bone loss in Gruen zones 2, 6 and 7. RSA showed minor micromotion of the stem: mean subsidence was 0.13 (95% CI: -0.28 to 0.01) mm and mean rotation around the longitudinal axis was 0.01º (95% CI: -0.1 to 0.39) after 2 years. INTERPRETATION: We conclude that substantial loss in proximal periprosthetic BMD cannot be prevented by the use of a novel type of short, curved stem, and forces appear to be transmitted distally. However, the stems showed very small migration-a characteristic of stable uncemented implants.

New animal model for assessment of functional laryngeal motor innervation.

OBJECTIVES: The functional motor innervation of the larynx is not fully understood because of the complexity of the peripheral neuroanatomy. Since the late 19th century, there has been controversy regarding the role of the superior laryngeal nerve, which may have wider motor projections than are currently acknowledged. The aim of this study was to develop a large animal model to characterize and quantify the functional motor input to the intrinsic laryngeal muscles. METHODS: We performed invasive electrophysiology (evoked electromyography) in normal pigs. RESULTS: The thyroarytenoid, lateral cricoarytenoid, and posterior cricoarytenoid muscles receive dual innervation from both the superior and recurrent laryngeal nerves, whereas the cricothyroid muscle is innervated only by the superior laryngeal nerve. CONCLUSIONS: The dual innervation pattern from both laryngeal nerves supports the concept of a laryngeal nerve plexus. The motor input through the external branch of the superior laryngeal nerve was surprisingly high. The animal model presented here may be used in future investigations of laryngeal reinnervation following nerve injury.

Calcium sulfate spinal cord scaffold: a study on degradation and fibroblast growth factor 1 loading and release.

Currently, there is no regenerative strategy for the spinal cord that is part of clinical standard of core. Current paths usually include combinations of scaffold materials and active molecules. In a recent study, a permanent dental resin scaffold for treatment of spinal cord injury was designed. The results from studies on rats were promising. However, for potential clinical use, a biodegradable scaffold material that facilitates drug delivery and the regeneration of the spinal cord needs to be developed. Also a biodegradable material is expected to allow a better evaluation of the efficacy of the surgical method. In this article, the suitability of hardened calcium sulfate cement (CSC) for use as degradable spinal cord scaffolds is investigated in bench studies and in vitro studies. Compressive strength, degradation and microstructure, and the loading capability of heparin-activated fibroblast growth factor 1 (FGF1) via soaking were evaluated. The CSC could easily be injected into the scaffold mold and the obtained scaffolds had sufficient strength to endure the loads applied during surgery. When hardened, the CSC formed a porous microstructure suitable for loading of active substances. It was shown that 10 min of FGF1 soaking was enough to obtain a sustained active FGF1 release for 20-35 days. The results showed that CSC is a promising material for spinal cord scaffold fabrication, since it is biodegradable, has sufficient strength, and allows loading and controlled release of active FGF1.

FGF1 containing biodegradable device with peripheral nerve grafts induces corticospinal tract regeneration and motor evoked potentials after spinal cord resection.

PURPOSE: Repairing the spinal cord with peripheral nerve grafts (PNG) and adjuvant acidic fibroblast growth factor (FGF1) has previously resulted in partial functional recovery. To aid microsurgical placement of PNGs, a graft holder device was previously developed by our group. In hope for a translational development we now investigate a new biodegradable graft holder device containing PNGs with or without FGF1. METHODS: Rats were subjected to a T11 spinal cord resection with subsequent repair using twelve white-to-grey matter oriented PNGs prepositioned in a biodegradable device with or without slow release of FGF1. Animals were evaluated with BBB-score, electrophysiology and immunohistochemistry including anterograde BDA tracing. RESULTS: Motor evoked potentials (MEP) in the lower limb reappeared at 20 weeks after grafting. MEP responses were further improved in the group treated with adjuvant FGF1. Reappearance of MEPs was paralleled by NF-positive fibers and anterogradely traced corticospinal fibers distal to the injury. BBB-scores improved in repaired animals. CONCLUSIONS: The results continue to support that the combination of PNGs and FGF1 may be a regeneration strategy to reinnervate the caudal spinal cord. The new device induced robust MEPs augmented by FGF1, and may be considered for translational research.

The effects of different weight-bearing regimes on press-fit cup stability: a randomised study with five years of follow-up using radiostereometry.

PURPOSE: There is little evidence to support immediate weight bearing after uncemented total hip arthroplasty (THA). METHODS: Thirty-seven patients with unilateral osteoarthritis of the hip received a press-fit cup. Cup stability was assessed with radiostereometry (RSA) over five years. Patients were randomised to immediate full weight bearing, or partial weight bearing for three months. RESULTS: At five years, we found no difference in micro-motion as assessed with radiostereometry. Numerically, there was more proximal translation and increased inclination with immediate weight bearing, but these values barely exceeded the precision limit for the method. Pooled data for the two groups revealed translations of 0.1-0.3 mm and rotations of 0.2-0.3° over the five year follow-up period. CONCLUSIONS: We found no adverse effects of immediate weight bearing after THA in relation to stability of these press-fit cups. Early mobilisation might have other advantages.

Electrical short-circuit in ß-cells from a patient with non-insulinoma pancreatogenous hypoglycemic syndrome (NIPHS): a case report.

INTRODUCTION: Non-insulinoma pancreatogenous hypoglycemic syndrome is a rare disorder among adults, and, to our knowledge, only about 40 cases have been reported in the literature. CASE PRESENTATION: The patient is a previously healthy 35-year-old Caucasian man. His symptoms began four years ago when he suddenly felt weakness in his legs and started sweating for unknown reasons. The symptoms worsened, and laboratory tests revealed hypoglycemia and hyperinsulinemia at the time of the symptoms. All diagnostics attempts using magnetic resonance imaging, computed tomography, and endoscopic ultrasound did not reveal any abnormalities. At this stage, surgical intervention was planned, and a distal 80% pancreatectomy was performed. The histopathologic and immunohistochemical investigations of the pancreas showed an increased number of islets of different sizes, more or less evenly distributed in the gland, but no insulinoma. Patch-clamp recordings from isolated pancreatic ß-cells showed that, even at a low glucose concentration (3 mmol/L), the ß-cell membrane was depolarized, and action potentials were seen. Surprisingly, in patch-clamp experiments, the addition of diazoxide had a marked effect on K-ATP channel activity and membrane potential, but no effect on insulin levels in vivo before surgery. CONCLUSION: This case report adds new information on the pathogenesis of non-insulinoma pancreatogenous hypoglycemic syndrome, as we performed an electrophysiologic characterization of isolated islet cells. We show, for the first time, that ß-cells isolated from a non-insulinoma pancreatogenous hypoglycemic syndrome patient are constantly depolarized, even at low glucose levels, but display normal K-ATP channel physiology.

Periprosthetic bone mineral density and fixation of the uncemented CLS stem related to different weight bearing regimes: A randomized study using DXA and RSA in 38 patients followed for 5 years.

BACKGROUND AND PURPOSE: There is no consensus on the best rehabilitation regime after uncemented total hip arthroplasty. Theoretically, bone ingrowth into the implant should benefit from initial partial weight bearing. We investigated whether the degree of postoperative weight bearing influences the periprosthetic bone mineral density (BMD) and/or the stability of the CLS stem. PATIENTS AND METHODS: 38 patients received an uncemented CLS stem and were randomized to either unrestricted postoperative weight bearing or to partial weight bearing for 3 months. Periprosthetic BMD was measured in the 7 Gruen zones with DXA and the stability of the femoral stem was assessed by radiostereometric analysis (RSA) after surgery and at 3, 12, 24, and 60 months. RESULTS: Periprosthetic BMD was not influenced by the type of postoperative weight bearing. BMD was reduced by 8-15% in all Gruen zones at 3 months. Restoration toward initial BMD was observed in all zones except in zone 7 (calcar region), where BMD was reduced by 22% at 5 years. Immediate weight bearing after surgery had no influence on the stability of the CLS stem, as assessed by RSA. INTERPRETATION: Immediate full weight bearing after uncemented total hip arthroplasty is safe. There is no difference in the periprosthetic BMD or in stability of the stem as measured by RSA compared to partial weight bearing for 3 months. BMD is reduced by more than 20% in the calcar region around a CLS stem after 5 years.

Peripheral nerve grafts in a spinal cord prosthesis result in regeneration and motor evoked potentials following spinal cord resection.

PURPOSE: To evaluate whether a standardized nerve graft bridging of a spinal cord injury gap in a device with white to grey matter projections allows regeneration and electrophysiological contact from supraspinal centers to the leg, since previous studies using nerve grafts in combination with acidic fibroblast growth factor have been difficult to microsurgically reproduce. METHODS: A moulded prosthesis containing twelve peripheral nerve grafts with estimated pre-set projections guiding white tracts to grey matter replaced a spinal cord resection gap at level T11 in adult rats. The animals were evaluated with electrophysiology, morphology, immunohistochemistry and functional scoring. RESULTS: At six months postoperatively the grafts were found to be positioned at the desired locations, motor evoked potentials were detected in 80% of the animals subjected to nerve graft bridging. Morphology and immunohistochemical analysis revealed numerous de novo axons in the grafts, which possibly reached into the spinal cord on the other side. CONCLUSION: Replacing the resected spinal cord with oblique peripheral nerve grafts results in spinal cord regeneration and positive motor evoked potential. Transplantation of nerve grafts organized in a prosthesis is re-producible, sustains desired projections and ensures transverse ends towards the spinal cord surface and may be useful in the future.

Diagnosis and prognosis of iatrogenic injury of the recurrent laryngeal nerve.

OBJECTIVES: Following perioperative injury to a macroscopically intact recurrent laryngeal nerve (RLN), there are two possible intraneural injury types: 1) axonal injury, including disruption of axons, and 2) conduction block, only affecting the Schwann cells and the nodes of Ranvier. In this study, it was hypothesized that the functional outcome after RLN injury may depend on the type of nerve injury. METHODS: Fifteen patients with acute postoperative unilateral RLN paralysis were prospectively studied. Electrophysiological examination (laryngeal electromyography) was used to differentiate between the two types of nerve injury. Vocal fold motions were monitored by repeated laryngoscopy during the study period (up to 6 months). Three of the patients with axonal injury were treated with the regeneration-promoting agent nimodipine. RESULTS: The patients with conduction block all recovered normal vocal fold motion, whereas patients with axonal injury within the nerve had a significantly worse outcome. The 3 patients who were treated with nimodipine all recovered normal or near-normal vocal fold mobility despite the more severe axonal injury. CONCLUSIONS: In contrast to previous reports, our results show that laryngeal electromyography is a reliable tool for diagnosing the type of injury within the injured RLN, making it possible to predict the functional outcome in these patients. On the basis of the results, a future randomized study on nimodipine treatment for RLN axonal injury is suggested.

Stability of cemented in-line pegged glenoid compared with keeled glenoid components in total shoulder arthroplasty.

BACKGROUND: Considerable interest has been focused on the design of the glenoid component used in total shoulder arthroplasty in order to reduce the risk of loosening. One design-related feature that has attracted attention is whether to use pegged or keeled cemented glenoid components. The main purpose of this study was to compare the fixation of cemented keeled glenoid components with that of cemented in-line pegged glenoid components. METHODS: In a prospective randomized study, we compared the stability of cemented, all-polyethylene, keeled glenoid components and cemented, all-polyethylene, in-line three-pegged glenoid components by radiostereometric analysis. Twenty-seven shoulders in twenty-five patients with osteoarthritis (twenty-two shoulders had primary and five shoulders had secondary osteoarthritis) were included. There were sixteen women and nine men, and the mean age was sixty-four years. Radiostereometric analysis and conventional radiographs were carried out at five days, at four months, and at one and two years postoperatively. RESULTS: The mean Constant and Murley score preoperatively and two years postoperatively was 25 and 70, respectively, for shoulders with the keeled glenoid component and 22 and 70 for the shoulders with a pegged component. No significant difference was detected between groups with regard to the average micromigration of the glenoid components at any of the time points. The average translation was <1 mm, while the median value was <0.3 mm at two years, with no significant difference between the different axes. In five shoulders (three with the keeled component and two with the pegged component), translation at two years was >1 mm. In fourteen shoulders (eight with the keeled and six with the pegged component), the rotation around one or several axes was >2 degrees . We were not able to detect any specific pattern with regard to movement for either type of component nor were we able to detect any difference between the two types of components in the way they migrated, if migration occurred. CONCLUSIONS: Cemented all-polyethylene keeled or in-line three-pegged glenoid components appear to have similar stability during the first two years after surgery. Studies with a longer follow-up period are needed to relate these findings to long-term clinical and radiographic outcomes.

Preserved regeneration and functional recovery of the injured recurrent laryngeal nerve after secondary surgical repair in adult rats.

OBJECTIVES: Transection of the recurrent laryngeal nerve (RLN) is accompanied by poor functional recovery, despite primary repair, because of regeneration difficulties. Nimodipine can promote regeneration, but it is not yet clear whether preoperative treatment is necessary. It is also not clear whether surgical repair following RLN injury may be performed in a second procedure, with preserved regeneration. This study investigated the time window for secondary surgical repair of the transected RLN and the need for preoperative administration of nimodipine. METHODS: In adult rats, the left RLN was transected and repaired at time intervals up to 3 weeks after transection, in combination with nimodipine treatment starting either before or after the operation. Regeneration and neuromuscular recovery were assessed by electrophysiology, retrograde tracing, and immunohistochemistry. RESULTS: Similar (whether 0, 2, or 7 days) regenerative results were obtained when the RLN was repaired up to 1 week after injury, given nimodipine administration, whereas fewer motor neurons managed to regenerate after nerve repair at 3 weeks after the initial transection. No beneficial effect was detected from preoperative nimodipine administration. CONCLUSIONS: Provided that nimodipine is administered, surgical reconstruction of the RLN can be performed within 1 week after the initial nerve trauma, with preserved neuromuscular function. Nimodipine may be administered at the time of RLN transection injury.

Collateral reinnervation by the superior laryngeal nerve after recurrent laryngeal nerve injury.

This study investigates the role of the intact superior laryngeal nerve (SLN) in the reinnervation process of one of the laryngeal muscles, the posterior cricoarytenoid muscle (PCA), following recurrent laryngeal nerve (RLN) injury. Using a chronic RLN injury model in the adult rat, PCA reinnervation was assessed by retrograde double-tracing techniques in combination with electrophysiology and immunohistochemistry of muscle sections. The results demonstrate that the PCA receives dual innervation from both laryngeal nerves even in the uninjured system. Functionally significant collateral reinnervation originates from intact SLN fibers following RLN injury, mainly due to intramuscular sprouting rather than by recruitment of more motor neurons. This may be important when choosing surgical and/or medical treatment for patients with RLN injury.

Nimodipine improves reinnervation and neuromuscular function after injury to the recurrent laryngeal nerve in the rat.

OBJECTIVES: Injury of the recurrent laryngeal nerve (RLN) is associated with a high degree of neuronal survival, but leads to various levels of vocal fold motion impairment or laryngeal synkinesis, which has been attributed to misdirected reinnervation of the target muscles in the larynx or aberrant, competing reinnervation from adjacent nerve fibers. The aim of the present study was to evaluate the impact of the regeneration-promoting agent nimodipine on reinnervation and neuromuscular function following RLN crush injury. METHODS: Sixty adult rats were randomized into nimodipine-treated or untreated groups and then underwent RLN crush injury. Reinnervation of the posterior cricoarytenoid muscle (PCA) was assessed by electrophysiological examination, retrograde tracing of lower motor neurons before and after injury, and quantification of neuromuscular junctions in the PCA muscle. RESULTS: At 6 weeks after injury, the nimodipine-treated animals showed significantly enhanced neuromuscular function and also demonstrated a higher number of motor neurons in the brain stem that had reinnervated the PCA, compared to the untreated animals. The somatotopic organization of ambiguus motor neurons innervating the larynx was similar before injury and after reinnervation. CONCLUSIONS: Nimodipine improves regeneration and neuromuscular function following RLN injury in the adult rat, and could be of use in future strategies following RLN injury.