Vascularized Olecranon Bone Graft: An Anatomical Study and Novel Technique.

PURPOSE: Autologous bone grafting is commonly used in reconstructive hand surgery. Various sources of nonvascularized autologous bone grafts have been described in the literature. However, in some situations, a vascularized bone graft may be needed. Popular vascularized bone grafts are taken from the distal radius, iliac crest, and medial femoral condyle. The purpose of this study was to examine the feasibility of harvesting a free vascularized bone flap from the proximal ulna. METHODS: Latex was injected via the brachial artery to facilitate visualization of perforators in 10 cadaveric specimens. Dissections were performed of the olecranon; all periosteal perforators were noted, and their lengths and diameters recorded. Corticocancellous bone flaps with their supplying pedicles were harvested. Three additional fresh specimens were injected with india ink via the pedicles to demonstrate perfusion of the harvested bone flap. RESULTS: Consistent vascular anatomy supplied the olecranon. A perforator from the posterior ulnar recurrent artery supplied the proximal ulna and olecranon, from which a vascularized bone flap can be harvested. Branches to the flexor carpi ulnaris muscle may allow chimeric flaps to be harvested. Average pedicle length was 5.8 cm and average pedicle diameter was 2.4 mm. India ink injection of the pedicles showed perfusion of the periosteum as well as intraosseous cancellous bone. CONCLUSIONS: A vascularized olecranon free flap can be harvested based on the posterior ulnar recurrent artery. Vascular anatomy is consistent and flap harvest is simple and straightforward in all cadaveric specimens. CLINICAL RELEVANCE: A vascularized olecranon free flap represents a potential new surgical option when vascular bone flap reconstruction is considered.

Distally Based Pedicled Flexor Carpi Ulnaris Muscle Flap: An Anatomical Study and Clinical Application.

BACKGROUND: Proximally based, pedicled flexor carpi ulnaris (FCU) muscle flap has been described previously for soft tissue coverage of the proximal forearm and elbow. No studies have been done on the distal muscular perforators and its use as a distally based flap. METHODS: Ten fresh-frozen cadaveric dissections were done. Specimens were injected with latex to facilitate identification of the perforators. Distal muscular perforators were dissected and distances of the pedicles from the distal wrist crease and ulnar styloid were measured and recorded. A clinical case is also presented where a distally based FCU muscle flap was used for coverage in a patient with median nerve neuroma. RESULTS: A distal muscular perforator and a second more proximal perforator were identified in all specimens. The average distance from the most distal muscular perforator to the ulnar styloid was 3.0 cm. The average distance to the wrist crease was 4.6 cm. The more proximal perforators had an average distance to the ulnar styloid and wrist crease of 7.3 cm and 8.8 cm, respectively. At 7 months post-op, the patient who underwent median nerve neurolysis and coverage with pedicled FCU flap had much improved sensation, with complete resolution of pain and tingling, and without any functional deficits. CONCLUSIONS: The use of a distally based FCU muscle flap is a good option for soft tissue coverage of the distal forearm, wrist, and hand. The distal muscular perforators from the ulnar artery exhibit a relatively consistent anatomy.

Repair of the musculocutaneous nerve using the vagus nerve as donor by helicoid end-to-side technique: an experimental study in rats.

Although several donor nerves can be chosen to repair avulsed brachial plexus nerve injury, available nerves are still limited. The purpose of this study is to validate whether the vagus nerve (VN) can be used as a donor. Eighteen Sprague-Dawley male rats were divided into three groups (n = 6). The right musculocutaneous nerve (McN) was transected with differing subsequent repair. (1) HS-VN group: a saphenous nerve (SN) graft-end was helicoidally wrapped round the VN side (epi-and perineurium was opened) with a 30 ° angle, distal SN end was coapted to the McN with end-to-end repair. (2) EE-PN group: a SN was interpositionally grafted between the transected phrenic nerve (PN) and the McN by end-to-end coaptation. (3) Sham control group: McN was transected and not repaired and postoperative vital signs were checked daily. At three months, electrophysiology, tetanic force, wet biceps muscle weight, and histology were evaluated. Every tested mean value in HS-VN group was significantly greater than the EE-PN or the sham control groups (p < 0.05 or p < 0.005). The mean recovery ratio of regenerated nerve fibers was 96% and, in HS-VN group, the mean recovery ratio of CMAP was 79%. No vital signs changed in any group. There was no statistical difference (p > 0.5) between the mean VN nerve-fiber numbers of the segments proximal (2237 ± 134) and distal (2150 ± 156) to the VN graft-attachment site. Histological analysis revealed no axon injury or intraneural scarring at any point along the VN. This study demonstrated that VN is a practical and reliable donor nerve for end-to-side nerve transfer. © 2017 Wiley Periodicals, Inc.

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.

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.

Comparison of Peripheral Nerve Axonal Area Differences in Central and Peripheral Zones of Injured and Repaired Nerves.

BACKGROUND: Histological analysis remains a cornerstone approach for the investigation of peripheral nerve regeneration. This study investigates a newly recognized histological difference between peripheral and central zones within the regenerating nerve trunks. PURPOSE: The purpose of the study was to determine if the nerve axonal area (NXA) in regenerating peripheral nerves differs within central and peripheral areas, when viewed in cross-section. METHODS: A total of 14 rats were divided into two groups, and subjected to different injuries to the right sciatic nerve. Group 1: Transection injury with immediate repair. Group 2: Crush injury without any treatment. The left sciatic nerve was left uninjured and served as a control in each rat. Following 4 weeks of recovery, nerve trunk cross-sections were prepared. Computerized techniques were then employed to divide nerve sections into central and peripheral zones and calculate corresponding NXA values for subsequent statistical analysis. RESULTS: NXA of injured nerves was greater within peripheral as compared with the central zones, independent of injury type (p < 0.05). No statistically significant difference existed within the control groups or between the injury methods with regards to NXA regeneration extent. CONCLUSION: NXA in regenerating peripheral nerves was greater in the peripheral zones than within the central zones.

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.

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.

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.

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.

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 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 correlation between calcium intensity and histopathological changes in brachial plexus nerve injuries.

BACKGROUND: After nerve injury, an influx of calcium exceeds the homeostatic capacity, which damages peripheral nerves. Previous studies identified that following nerve crush, function improves as calcium levels normalize. METHODS: Electrophysiological analysis was performed to measure the compound muscle action potential of 15 patients' damaged nerves. These samples were evaluated for calcium level and also stained with a Luxol fast blue and neurofilament antibodies to evaluate the myelin sheath and neurofilaments of the nerves. Based on the Sunderland scale, we identified three exclusive types of peripheral nerve injury groups. RESULTS: There was a correlation between histopathological damage and calcium levels of 0.81 (p < 0.005). The average relative fluorescence units (RFUs) was 235.28 ± 19, which corresponds to 5.3 × 10⁻7 M of calcium, five times the normal value. CONCLUSION: Our study shows promising clinical implications via faster pathology results by the RFU technique. This approach of calcium staining, though still in clinical trials, offers significant clinical application, allowing physicians to get the clinically diagnostic nerve injury degree faster and will also facilitate better strategies for further treatment or future surgeries.

Cortical plasticity induced by different degrees of peripheral nerve injuries: a rat functional magnetic resonance imaging study under 9.4 Tesla.

BACKGROUND: Major peripheral nerve injuries not only result in local deficits but may also cause distal atrophy of target muscles or permanent loss of sensation. Likewise, these injuries have been shown to instigate long-lasting central cortical reorganization. METHODS: Cortical plasticity changes induced after various types of major peripheral nerve injury using an electrical stimulation technique to the rat upper extremity and functional magnetic resonance imaging (fMRI) were examined. Studies were completed out immediately after injury (acute stage) and at two weeks (subacute stage) to evaluate time affect on plasticity. RESULTS: After right-side median nerve transection, cortical representation of activation of the right-side ulnar nerve expanded intra-hemispherically into the cortical region that had been occupied by the median nerve representation After unilateral transection of both median and ulnar nerves, cortical representation of activation of the radial nerve on the same side of the body also demonstrated intra-hemispheric expansion. However, simultaneous electrical stimulation of the contralateral uninjured median and ulnar nerves resulted in a representation that had expanded both intra- and inter-hemispherically into the cortical region previously occupied by the two transected nerve representations. CONCLUSIONS: After major peripheral nerve injury, an adjacent nerve, with similar function to the injured nerve, may become significantly over-activated in the cortex when stimulated. This results in intra-hemispheric cortical expansion as the only component of cortical plasticity. When all nerves responsible for a certain function are injured, the same nerves on the contralateral side of the body are affected and become significantly over-activated during a task. Both intra- and inter-hemispheric cortical expansion exist, while the latter dominates cortical plasticity.

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.

Transhemispheric cortical plasticity following contralateral C7 nerve transfer: a rat functional magnetic resonance imaging survival study.

PURPOSE: To perform contralateral C7 nerve transfer in a controlled, survival rat functional magnetic resonance imaging model, so as to understand the extent of cortical plasticity after brachial plexus injury and surgical manipulation with this procedure. METHODS: A total of 24 rats divided into 3 groups underwent surgery followed by functional magnetic resonance imaging in this study. Group I rats served as sham controls. Group II injury rats underwent complete right brachial plexus root avulsion. Group III repair rats underwent complete right brachial plexus root avulsion and then contralateral C7 nerve transfer to the right median nerve. We assessed cortical response to median nerve stimulation at 0, 3, and 5 months after injury using functional magnetic resonance imaging at 9.4 T. We concurrently performed sensory and motor functional testing. RESULTS: We noted a progression in cortical activation in the repair rats over 0, 3, and 5 months. Initially, right median nerve stimulation in the repair group showed complete loss of activation in the contralateral somatosensory cortex. Nerve stimulation at 3 months produced primarily ipsilateral cortical activation; at 5 months, 3 patterns of cortical activation emerged: ipsilateral, bilateral, and contralateral activation. After right median nerve stimulation, injury rats maintained a lack of cortical activation and control rats maintained exclusive contralateral activation throughout all time points. Functional testing revealed a degree of return of sensory and motor function over time in the repair group compared with the injured group. CONCLUSIONS: A high degree of transhemispheric cortical plasticity occurred after contralateral C7 nerve transfer. There appears to be a predilection for the rat brain to restore the preinjury somatotopic representation of the brain. CLINICAL RELEVANCE: Understanding the cortical changes after nerve injury and repair may lead to specific pharmacologic or behavioral interventions that can improve functional outcomes.

Long-term vascular access ports as a means of sedative administration in a rodent fMRI survival model.

The purpose of this study is to develop a rodent functional magnetic resonance imaging (fMRI) survival model with the use of heparin-coated vascular access devices. Such a model would ease the administration of sedative agents, reduce the number of animals required in survival experiments and eliminate animal-to-animal variability seen in previous designs. Seven male Sprague-Dawley rats underwent surgical placement of an MRI-compatible vascular access port, followed by implantable electrode placement on the right median nerve. Functional MRI during nerve stimulation and resting-state functional connectivity MRI (fcMRI) were performed at times 0, 2, 4, 8 and 12 weeks postoperatively using a 9.4T scanner. Anesthesia was maintained using intravenous dexmedetomidine and reversed using atipamezole. There were no fatalities or infectious complications during this study. All vascular access ports remained patent. Blood oxygen level dependent (BOLD) activation by electrical stimulation of the median nerve using implanted electrodes was seen within the forelimb sensory region (S1FL) for all animals at all time points. The number of activated voxels decreased at time points 4 and 8 weeks, returning to a normal level at 12 weeks, which is attributed to scar tissue formation and resolution around the embedded electrode. The applications of this experiment extend far beyond the scope of peripheral nerve experimentation. These vascular access ports can be applied to any survival MRI study requiring repeated medication administration, intravenous contrast, or blood sampling.