TLR4-MyD88 signaling is involved in the spinal neurons during the full length of recovery from transection of the motor branch of the femoral nerve in mice.

This study was designed to see the expression of toll-like receptor 4 (TLR4) and downstream molecules including myeloid differentiation factor 88 (MyD88) and interleukin 1-ß (IL-1ß) in the spinal cord as peripheral nerve injury recovered in mice. We established a model of femoral nerve injury (FNI) in C57BL/6 mice by transection of the motor branch of the femoral nerve, followed by retrograde labeling to show the according motor neurons in the anterior horn of the spinal cord pars lumbar. We observed the motor function recovery of the injured hind limbs using behavioral tests. The expression of TLR4, MyD88, and IL-1ß was examined by immunofluorescent staining and western blot. According to the behavior test, the FNI animals fully recovered within 6-8 weeks. TLR4, MyD88, and IL-1ß were expressed in the ventral horn of the spinal cord both at 72 h till 6 weeks after the femoral nerve transection surgery, and these proteins were mostly co-localized with neurons. IL-1ß also tended to rise in the same surgery groups, but more intimate with microglia surrounding nearby retrograde labeled neurons. And western blot results were consistent with histological findings. The results indicate that peripheral nerve injury may induce innate immune reactions of the central neurons and critical signaling like TLR4/MyD88 in the spinal cord may reflect the recovery of the injury. These findings suggest that peripheral nerve injury triggered the TLR4/MyD88 signal in the soma of spinal neurons may be involved in function and nerve restoration through neuron-glia crosstalk.

Prohibitin 1 is essential to preserve mitochondria and myelin integrity in Schwann cells.

In peripheral nerves, Schwann cells form myelin and provide trophic support to axons. We previously showed that the mitochondrial protein prohibitin 2 can localize to the axon-Schwann-cell interface and is required for developmental myelination. Whether the homologous protein prohibitin 1 has a similar role, and whether prohibitins also play important roles in Schwann cell mitochondria is unknown. Here, we show that deletion of prohibitin 1 in Schwann cells minimally perturbs development, but later triggers a severe demyelinating peripheral neuropathy. Moreover, mitochondria are heavily affected by ablation of prohibitin 1 and demyelination occurs preferentially in cells with apparent mitochondrial loss. Furthermore, in response to mitochondrial damage, Schwann cells trigger the integrated stress response, but, contrary to what was previously suggested, this response is not detrimental in this context. These results identify a role for prohibitin 1 in myelin integrity and advance our understanding about the Schwann cell response to mitochondrial damage.

Abnormal prion protein deposits with high seeding activities in the skeletal muscle, femoral nerve, and scalp of an autopsied case of sporadic Creutzfeldt-Jakob disease.

We report the general autopsy findings of abnormal prion protein (PrP) deposits with their seeding activities, as assessed by the real-time quaking-induced conversion (RT-QuIC) method, in a 72-year-old female patient with sporadic Creutzfeldt-Jakob disease (sCJD). At 68 years of age, she presented with gait disturbance and visual disorders. Electroencephalography showed periodic synchronous discharge. Myoclonus was also observed. A genetic test revealed that PRNP codon 129 was methionine/methionine (MM). She died of pneumonia three years and four months after disease onset, and a general autopsy was performed. The brain weighed 650 g and appeared markedly atrophic. Immunohistochemistry for PrP revealed synaptic PrP deposits and coarse PrP deposits in the cerebral cortices, basal ganglia, cerebellum, and brainstem. Western blot analysis identified type 1 proteinase-K-resistant PrP in frontal cortex samples. PrP deposits were also observed in systemic organs, including the femoral nerve, psoas major muscle, abdominal skin, adrenal medulla, zona reticularis of the adrenal gland, islet cells of the pancreas, and thyroid gland. The RT-QuIC method revealed positive seeding activities in all examined organs, including the frontal cortex, femoral nerve, psoas major muscle, scalp, abdominal skin, adrenal gland, pancreas, and thyroid gland. The following 50% seeding dose (SD50 ) values were 9.5 (frontal cortex); 8 ± 0.53 (femoral nerve); 7 ± 0.53 (psoas major muscle); and 7.88 ± 0.17 (scalp). The SD50 values for the adrenal gland, dermis, pancreas, and thyroid gland were 6.12 ± 0.53, 5.25, 4.75, and 4.5, respectively. PrP deposits in general organs may be associated with long-term disease duration. This case indicated the necessity for general autopsies in sCJD cases to establish strict infection control procedures for surgical treatment and to examine certain organs.

Immunohistochemical Femoral Nerve Study Following Bisphosphonates Administration.

Background and objectives: Bisphosphonates represent selective inhibitors of excess osteoblastic bone resorption that characterizes all osteopathies, targeting osteoclasts and their precursors. Their long-term administration in postmenopausal women suffering from osteoporosis has resulted in neural adverse effects. The current study focuses on the research of possible alterations in the femoral nerve, caused by bisphosphonates. We hypothesized that bisphosphonates, taken orally (per os), may produce degenerative changes to the femoral nerve, affecting lower-limb posture and walking neuronal commands. Materials and Methods: In order to support our hypothesis, femoral nerve specimens were extracted from ten female 12-month-old Wistar rats given 0.05 milligrams (mg) per kilogram (kg) of body weight (b.w.) per week alendronate per os for 13 weeks and from ten female 12-month-old Wistar rats given normal saline that were used as a control group. Specimens were studied using immunohistochemistry for selected antibodies NeuN (Neuronal Nuclear Protein), a protein located within mature, postmitotic neural nucleus, and cytosol and Sox10 (Sex-determining Region Y (SRY) - High-Motility Group (HMG) - box 10). The latter marker is fundamental for myelination of peripheral nerves. Obtained slides were examined under a light microscope. Results: Samples extracted from rats given alendronate were more Sox10 positive compared to samples of the control group, where the marker's expression was not so intense. Both groups were equally NeuN positive. Our results are in agreement with previous studies conducted under a transmission electron microscope. Conclusions: The suggested pathophysiological mechanism linked to histological alterations described above is possibly related to toxic drug effects on Schwann and neuronal cells. Our hypothesis enhances the existing scientific evidence of degenerative changes present on femoral nerve following bisphosphonates administration, indicating a possible relationship between alendronate use and neuronal function.

Effect of ischemic preconditioning and changing inspired O2 fractions on neuromuscular function during intense exercise.

The aim of the present study was to determine whether ischemic preconditioning (IPC)-mediated effects on neuromuscular function are dependent on tissue oxygenation. Eleven resistance-trained males completed four exercise trials (6 sets of 11 repetitions of maximal effort dynamic single-leg extensions) in either normoxic [fraction of inspired oxygen (FIO2): 21%) or hypoxic FIO2: 14%] conditions, preceded by treatments of either IPC (3 × 5 min bilateral leg occlusions at 220 mmHg) or sham (3 × 5 min at 20 mmHg). Femoral nerve stimulation was utilized to assess voluntary activation and potentiated twitch characteristics during maximal voluntary contractions (MVCs). Tissue oxygenation (via near-infrared spectroscopy) and surface electromyography activity were measured throughout the exercise task. MVC and twitch torque declined 62 and 54%, respectively (MVC: 96 ± 24 N·m, Cohen's d = 2.9, P < 0.001; twitch torque: 37 ± 11 N·m, d = 1.6, P < 0.001), between pretrial measurements and the sixth set without reductions in voluntary activation (P > 0.21); there were no differences between conditions. Tissue oxygenation was reduced in both hypoxic conditions compared with normoxia (P < 0.001), with an even further reduction of 3% evident in the hypoxic IPC compared with the sham trial (mean decrease 1.8 ± 0.7%, d = 1.0, P < 0.05). IPC did not affect any measure of neuromuscular function regardless of tissue oxygenation. A reduction in FIO2 did invoke a humoral response and improved muscle O2 extraction during exercise, however, it did not manifest into any performance benefit.NEW & NOTEWORTHY Ischemic preconditioning did not affect any facet of neuromuscular function regardless of the degree of tissue oxygenation. Reducing the fraction of inspired oxygen induced localized tissue deoxygenation, subsequently invoking a humoral response, which improved muscle oxygen extraction during exercise. This physiological response, however, did not manifest into any performance benefits.

Vibration-induced depression in spinal loop excitability revisited.

KEY POINTS: While it has been well described that prolonged vibration locally applied to a muscle or its tendon (up to 1 h) decreases spinal loop excitability between homonymous Ia afferents and motoneurons, the involved mechanisms are not fully understood. By combining electrophysiological methods, this study aimed to provide new insights into the mechanisms involved in soleus decreased spinal excitability after prolonged local vibration. We report that prolonged vibration induces a decrease in motoneuron excitability rather than an increase in presynaptic mechanisms (as commonly hypothesized in the current literature). The present results may help to design appropriate clinical intervention and could reinforce the interest in vibration as a treatment for spastic patients who are characterized by spinal hyper-excitability responsible for spasms and long-lasting reflexes. ABSTRACT: The mechanisms that can explain the decreased spinal loop excitability in response to prolonged local vibration (LV), as assessed by the H-reflex, remain to be precisely determined. This study provides new insights into how prolonged Achilles' tendon LV (30 min, 100 Hz) acutely interacts with the spinal circuitry. The roles of presynaptic inhibition exerted on Ia afferents (Experiment A, n = 15), neurotransmitter release at the synapse level (Experiment B, n = 11) and motoneuron excitability (Experiment C, n = 11) were investigated in soleus. Modulation of presynaptic inhibition was assessed by conditioning the soleus H-reflex (tibial nerve electrical stimulation) with fibular nerve (D1 inhibition) and femoral nerve (heteronymous facilitation, HF) electrical stimulations. Potential vibration-induced changes in neurotransmitter depletion at the Ia afferent terminals was assessed through paired stimulations applied over the tibial nerve (HD). Intrinsic motoneuron excitability was assessed with thoracic motor evoked potentials (TMEPs) in response to electrical stimulation over the thoracic spine. Non-conditioned H-reflex was depressed by ∼60% after LV (P < 0.001), while D1 and HF H-reflexes increased by ∼75% after LV (P = 0.03 and 0.06, respectively). In Experiment B, HD remained unchanged after LV (P = 0.80). In Experiment C, TMEPs were reduced by ∼13% after LV (P = 0.01). Overall, presynaptic mechanisms do not seem to be involved in the depression of spinal excitability after LV. It rather seems to rely, at least in part, on a decrease in intrinsic motoneuron excitability. These results may have implications in reducing spinal hyper-excitability in spastic patients.

Histopathologic changes inside the lateral femoral cutaneous nerve obtained from patients with persistent symptoms of meralgia paresthetica.

BACKGROUND: In patients with persistent symptoms of meralgia paresthetica, a neurectomy of the lateral femoral cutaneous nerve (LFCN) can be performed to alleviate pain symptoms. The neurectomy procedure can be performed either as a primary procedure or after failure of a previously performed neurolysis or decompression of the LFNC (secondary neurectomy). The goal of the present study was to quantify the histopathologic changes inside the LFCN obtained from patients with persistent symptoms of meralgia paresthetica, and specifically to compare to what extend these changes are present after primary versus secondary neurectomy. METHODS: A total of 39 consecutive cases were analyzed microscopically: in 29 cases, the neurectomy had been performed as primary procedure, in 10 cases, after failed neurolysis. Intraneural changes were quantified for the (1) thickening of perineurium, (2) deposition of mucoid, and (3) percentage of collagen. Analysis was performed at three levels: proximal to, at, and distal to the previous site of compression. In addition, correlations were investigated for the duration of symptoms and the body mass index (BMI) of the patient. RESULTS: Intraneural changes were found consistently in all cases. There was no significant difference for the primary and secondary neurectomy groups. There was also no relation with the previous site of compression. There was a weak correlation between the occurrence of intraneural changes and the duration of symptoms, although this difference was not statistically significant. CONCLUSIONS: Histopathological changes in this study were found in all patients with persistent symptoms of meralgia paresthetica regardless of a previously performed neurolysis procedure. This finding suggests that the intraneural changes that occur in persistent meralgia paresthetica are largely irreversible and support the surgical strategy of neurectomy as an alternative to neurolysis, also for primary surgical treatment and not only after failure of neurolysis.

Spread of injectate around hip articular sensory branches of the femoral nerve in cadavers.

BACKGROUND: Anatomical knowledge dictates that regional anaesthesia after total hip arthroplasty requires blockade of the hip articular branches of the femoral and obturator nerves. A direct femoral nerve block increases the risk of fall and impedes mobilisation. We propose a selective nerve block of the hip articular branches of the femoral nerve by an ultrasound-guided injection in the plane between the iliopsoas muscle and the iliofemoral ligament (the iliopsoas plane). The aim of this study was to assess whether dye injected in the iliopsoas plane spreads to all hip articular branches of the femoral nerve. METHODS: Fifteen cadaver sides were injected with 5 mL dye in the iliopsoas plane guided by ultrasound. Dissection was performed to verify the spread of injectate around the hip articular branches of the femoral nerve. RESULTS: In 10 dissections (67% [95% confidence interval: 38-88%]), the injectate was contained in the iliopsoas plane staining all hip articular branches of the femoral nerve without spread to motor branches. In four dissections (27% [8-55%]), the injection was unintentionally made within the iliopectineal bursa resulting in secondary spread. In one dissection (7% [0.2-32%]) adhesions partially obstructed the spread of dye. CONCLUSION: An injection of 5 mL in the iliopsoas plane spreads around all hip articular branches of the femoral nerve in 10 of 15 cadaver sides. If these findings translate to living humans, injection of local anaesthetic into the iliopsoas plane could generate a selective sensory nerve block of the articular branches of the femoral nerve without motor blockade.

The Lateral Femoral Cutaneous Nerve: Description of the Sensory Territory and a Novel Ultrasound-Guided Nerve Block Technique.

BACKGROUND AND OBJECTIVES: Nerve blockade of the lateral femoral cutaneous (LFC) nerve provides some analgesia after hip surgery. However, knowledge is lacking about the extent of the cutaneous area anesthetized by established LFC nerve block techniques, as well as the success rate of anesthetic coverage of various surgical incisions. Nerve block techniques that rely on ultrasonographic identification of the LFC nerve distal to the inguinal ligament can be technically challenging. Furthermore, the branching of the LFC nerve is variable, and it is unknown if proximal LFC nerve branches are anesthetized using the current techniques. The primary aim of this study was to investigate a novel ultrasound-guided LFC nerve block technique based on injection into the fat-filled flat tunnel (FFFT), which is a duplicature of the fascia lata between the sartorius and the tensor fasciae latae muscle, in order to assess the success rate of anesthetizing the proximal LFC nerve branches and covering of the different surgical incisions used for hip surgery. METHODS: First, a cadaveric study was conducted in order to identify an FFFT injection technique that would provide adequate injectate spread to the proximal LFC nerve branches. Second, a clinical study was conducted in a group of 20 healthy volunteers over 2 consecutive days. On trial day 1, successful complete anesthesia of the LFC nerve was defined by performing a suprainguinal fascia iliaca block bilaterally in each subject. On trial day 2, a triple-blind randomized controlled trial compared the effect of the novel ultrasound-guided LFC nerve block technique for bupivacaine versus placebo. The primary end point was the success rate of anesthesia of the proximal cutaneous area innervated by the LFC nerve for the FFFT injection with bupivacaine versus placebo. RESULTS: Adequate spread of injectate to the proximal LFC nerve branches in cadavers was obtained by injecting 10 mL with dynamic needle-tip tracking in the FFFT. Application of this technique in the randomized controlled trial provided anesthesia of the lateral thigh with a success rate of 95% (95% confidence interval, 73.9%-99.8%) for the active side and 0% for placebo (P < 0.001). The proximal branches were anesthetized with a success rate of 68% (95% confidence interval, 43.4%-87.4%) on the active side. The proximal extent of the anesthetized cutaneous area was on average 7.9 cm distal to the greater trochanter. CONCLUSIONS: This novel LFC nerve block technique is easy and quick and reliably produces anesthesia of the lateral thigh. The greater trochanter is rarely included in the area of anesthesia, which reduces the coverage of each specific surgical incision. The success rate of 68% in anesthetizing the proximal nerve branches must be further evaluated by future research.

Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport.

Although α-synuclein (αSyn) has been linked to Parkinson's disease (PD), the mechanisms underlying the causative role in PD remain unclear. We previously proposed a model for a transportable microtubule (tMT), in which dynein is anchored to a short tMT by LIS1 followed by the kinesin-dependent anterograde transport; however the mechanisms that produce tMTs have not been determined. Our in vitro investigations of microtubule (MT) dynamics revealed that αSyn facilitates the formation of short MTs and preferentially binds to MTs carrying 14 protofilaments (pfs). Live-cell imaging showed that αSyn co-transported with dynein and mobile ßIII-tubulin fragments in the anterograde transport. Furthermore, bi-directional axonal transports are severely affected in αSyn and γSyn depleted dorsal root ganglion neurons. SR-PALM analyses further revealed the fibrous co-localization of αSyn, dynein and ßIII-tubulin in axons. More importantly, 14-pfs MTs have been found in rat femoral nerve tissue, and they increased approximately 19 fold the control in quantify upon nerve ligation, indicating the unconventional MTs are mobile. Our findings indicate that αSyn facilitates to form short, mobile tMTs that play an important role in the axonal transport. This unexpected and intriguing discovery related to axonal transport provides new insight on the pathogenesis of PD.

Skeletal muscle bioenergetics during all-out exercise: mechanistic insight into the oxygen uptake slow component and neuromuscular fatigue.

Although all-out exercise protocols are commonly used, the physiological mechanisms underlying all-out exercise performance are still unclear, and an in-depth assessment of skeletal muscle bioenergetics is lacking. Therefore, phosphorus magnetic resonance spectroscopy (31P-MRS) was utilized to assess skeletal muscle bioenergetics during a 5-min all-out intermittent isometric knee-extensor protocol in eight healthy men. Metabolic perturbation, adenosine triphosphate (ATP) synthesis rates, ATP cost of contraction, and mitochondrial capacity were determined from intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), diprotonated phosphate ([Formula: see text]), and pH. Peripheral fatigue was determined by exercise-induced alterations in potentiated quadriceps twitch force (Qtw) evoked by supramaximal electrical femoral nerve stimulation. The oxidative ATP synthesis rate (ATPOX) attained and then maintained peak values throughout the protocol, despite an ~63% decrease in quadriceps maximal force production. ThusATPOX normalized to force production (ATPOX gain) significantly increased throughout the exercise (1st min: 0.02 ± 0.01, 5th min: 0.04 ± 0.01 mM·min-1·N-1), as did the ATP cost of contraction (1st min: 0.048 ± 0.019, 5th min: 0.052 ± 0.015 mM·min-1·N-1). Additionally, the pre- to postexercise change in Qtw (-52 ± 26%) was significantly correlated with the exercise-induced change in intramuscular pH (r = 0.75) and [Formula: see text] concentration (r = 0.77). In conclusion, the all-out exercise protocol utilized in the present study elicited a "slow component-like" increase in intramuscular ATPOX gain as well as a progressive increase in the phosphate cost of contraction. Furthermore, the development of peripheral fatigue was closely related to the perturbation of specific fatigue-inducing intramuscular factors (i.e., pH and [Formula: see text] concentration).NEW & NOTEWORTHY The physiological mechanisms and skeletal muscle bioenergetics underlying all-out exercise performance are unclear. This study revealed an increase in oxidative ATP synthesis rate gain and the ATP cost of contraction during all-out exercise. Furthermore, peripheral fatigue was related to the perturbation in pH and deprotonated phosphate ion. These findings support the concept that the oxygen uptake slow component arises from within active skeletal muscle and that skeletal muscle force generating capacity is linked to the intramuscular metabolic milieu.

The effect of femoral nerve block on fracture healing via expressions of growth factors and ß-catenin.

INTRODUCTION: Many patients of all ages are admitted to hospital due to bone fractures. The etiology of fracture has a very wide spectrum, ranging from motor accidents to pathological conditions such as tumors, osteoporosis, and others. Bone fracture healing is a well-programmed and well-organized process, but is also long and intractable. The outcome of this process is therefore affected by many factors, such as the patient's age, ethnicity, nutritional status, and extent of the fracture. At present, regional analgesic techniques are frequently applied in order to avoid the complications of systemic opioid administration, central block applications. Femoral block is one of the regional analgesic techniques frequently applied by anesthesiologists when the lower extremities are involved. In this study, we evaluated the effect of femoral nerve block on the healing of an experimental non-stabilized femur fracture via expression of TGF-ß, VEGF, and ß-catenin and bone histomorphometry in rats. MATERIAL AND METHODS: In the control group, only the femoral fracture was performed and the bone was not fixated, similarly as in other groups. In the One-Day Block group, a one-time femoral nerve block was applied after the femoral fracture. In the Three-Day Block group, a daily femoral nerve block was performed for three days after the femoral fracture. On Days 4, 7, and 13, femurs were excised. The bone sections were stained with hematoxylin-eosin to evaluate bone tissue and Safranin O to assess callus tissue, cartilaginous tissue, and new bone areas. TGF-ß, VEGF, and ß-catenin were assessed by immunohistochemistry. RESULTS: Histomorphometric analysis revealed that femoral block application had a positive impact on bone healing. TGF-ß expression in the One-Day and Three-Day Block Groups was significantly higher than in the control group at all times, as was also the case with VEGF expression. On day 13, ß-catenin expression was significantly higher in the Three-Day Block group than the others. CONCLUSIONS: The results of the study suggests that the applications of a femoral nerve block for perioperative analgesia, for either one day or three days, resulted in better and more rapid bone healing.

Human mesenchymal stem cells improve the neurodegeneration of femoral nerve in a diabetic foot ulceration rats.

Neuropathy is observed in 50% of diabetic patients with diabetic foot. This study attempted to explore the potential role of human mesenchymal stem cells-umbilical cord blood (hMSCs-UC) in femoral nerve (FN) neuropathy. The model rats were established by one time administration of streptozotocin and empyrosis on the dorsal hind foot. At 3d, 7d, 14d after treatment with hMSCs-UC or saline through left femoral artery, the serum NGF was examined by ELISA; NF-200 expression in FN was evaluated by immunohistochemistry; the diameter and roundness of FN, the ratio of capillary and muscular fiber of gastrocnemius were calculated under light microscope; and neuronal degenerations, such as demyelization, axonal atrophy, and loose arrangement of nerve fibers, were observed by electronic microscope. The results showed that, in hMSCs-UC-treated model rats, serum NGF was increased with higher positive rate of NF-200. Although the difference in FN diameters was not established among groups, improvement of roundness of FN was confirmed with increase in the numbers of capillary in FN-innervated gastrocnemius; additionally, degenerative neuropathy was significantly improved. Importantly, the functional study of electroneurogram (ENG) showed that, slowed conduction of FN in model rats was significantly restored by hMSCs-CU treatment. These data suggested that hMSCs-UC-treatment partially reverse the neuronal degeneration and nerve function of FN, which might be contributed by the upregulation of NGF with dramatic angiogenesis in FN-innervated gastrocnemius, consequently reversing neuronal structure and function, preventing or curing foot ulceration.

Incidence of intraneural needle insertion in ultrasound-guided femoral nerve block: A comparison between the out-of-plane versus the in-plane approaches / Incidencia de inserción intraneural en bloqueo femoral guiado por ecografía: comparación entre los enfoques en plano y fuera de plano

BACKGROUND: The optimal method of ultrasound-guided femoral nerve block (in-plane vs. out-of-plane) has not been established. We tested the hypothesis that the incidence of needle-nerve contact may be higher with out-of-plane than with in-plane needle insertion. METHODS: Forty-four patients with hip fracture (American Society of Anaesthesiologists physical status I-III) were randomized to receive the femoral block with an out-of-plane approach (needle inserted at a 45-60° angle 1 cm caudal to the midpoint of the ultrasound probe just above the femoral nerve) or with an in-plane technique (needle inserted 0.2-0.4 cm from the side of the probe lateral to the femoral nerve). Data collected included depth of needle insertion, response to nerve electric stimulation, and distribution of the injected volume in relation to the nerve (anterior vs. posterior, the latter assuming needle-nerve contact). The sensory block onset was tested at 20 min and block recovery and any neurologic symptoms were evaluated at 24 h. RESULTS: The incidence of needle-nerve contact was significantly higher with the out-of-plane approach (14/22 patients [64%]) than with the in-plane approach (2/22 patients [9%]) (p < 0.001) (OR = 17.5, 95% CI: 4-79). The rate of paraesthesia on crossing the fascia iliaca was similar in the two groups. All blocks uneventfully regressed; and no patient developed neurologic symptoms. CONCLUSIONS: Under the conditions of our study, needle-nerve contact during femoral nerve block occurs frequently with the out-of-plane approach. An in-plane approach results in an equally effective femoral block and less incidence of needle-nerve contact

ANTECEDENTES. No ha quedado establecido un método adecuado para el bloqueo femoral guiado por ecografía (en plano frente a fuera de plano). Probamos la hipótesis de que la incidencia del contacto entre la aguja y un nervio puede ser mayor en la inserción fuera de plano que en el abordaje en plano. MÉTODOS: Cuarenta y cuatro pacientes con fractura de cadera (estadio i-iii según la Sociedad Americana de Anestesiólogos) recibieron de manera aleatorizada un bloqueo femoral con un enfoque fuera de plano (inserción de la aguja en ángulo de 45-60° y 1 cm caudal a la sonda de ecografía sobre el nervio femoral) o con una técnica en plano (inserción de la aguja 0,2-0,4 cm desde el lado de la sonda lateral al nervio femoral). Entre los datos recopilados se incluían la profundidad de inserción de la aguja, la reacción a la estimulación nerviosa y la distribución del volumen inyectado en función del nervio (anterior comparado con posterior, este último con contacto entre la aguja y un nervio). Se analizó el inicio del bloqueo a los 20 min y se evaluaron la recuperación del bloqueo y los síntomas neurológicos después de 24 h. RESULTADOS: La incidencia del contacto entre la aguja y los nervios fue significativamente mayor con el enfoque fuera de plano (14/22 pacientes [64%]) que con el abordaje en plano (2/22 pacientes [9%]) (p < 0,001) (OR = 17,5 [95%]; IC: 4-79). El grado de parestesia en aponeurosis fue similar en ambos grupos. Se revirtieron todos los bloqueos sin incidentes; ningún paciente desarrolló síntomas neurológicos. CONCLUSIONES: En las condiciones de nuestro estudio, el contacto entre la aguja y un nervio durante el bloqueo femoral sucede a menudo con el enfoque fuera de plano. Un abordaje en plano tiene como resultado un bloqueo femoral igualmente efectivo, y una incidencia menor del contacto entre la aguja y un nervio

Delayed quadriceps weakness after continuous adductor canal block for total knee arthroplasty: a case report.

Adductor canal catheters have been shown to improve analgesia while maintaining quadriceps strength after total knee arthroplasty. We describe a patient who underwent total knee arthroplasty that likely had delayed quadriceps weakness as a result of a standard continuous 0.2% ropivacaine infusion at 8 ml/h within the adductor canal. On the day of surgery, the patient was able to stand and ambulate with minimal assistance. On the first post-operative day after surgery, approximately 20 h after starting the ropivacaine infusion, profound weakness of the quadriceps was noted with no ability to stand. Contrast subsequently injected through the adductor canal catheter under fluoroscopy revealed proximal spread approaching the common femoral nerve with as little as 2 ml of volume. This rare case of profound quadriceps weakness after a continuous adductor canal block reveals that local anaesthetic at the adductor canal can spread in a retrograde fashion towards the common femoral nerve, potentially resulting in quadriceps weakness.

Polysialic acid expression is not necessary for motor neuron target selectivity.

INTRODUCTION: Recovery after peripheral nerve lesions depends on guiding axons back to their targets. Polysialic acid upregulation by regrowing axons has been proposed recently as necessary for this target selectivity. METHODS: We reexamined this proposition using a cross-reinnervation model whereby axons from obturator motor neurons that do not upregulate polysialic acid regenerated into the distal femoral nerve. Our aim was to assess their target selectivity between pathways to muscle and skin. RESULTS: After simple cross-repair, obturator motor neurons showed no pathway preference, but the same repair with a shortened skin pathway resulted in selective targeting of these motor neurons to muscle by a polysialic acid-independent mechanism. CONCLUSION: The intrinsic molecular differences between motor neuron pools can be overcome by manipulation of their access to different peripheral nerve pathways such that obturator motor neurons preferentially project to a terminal nerve branch to muscle despite not upregulating the expression of polysialic acid.

PlexinA4 distribution in the adult rat spinal cord and dorsal root ganglia.

PlexinsA1-A4 participate in class 3 semaphorin signaling as co-receptors to neuropilin 1 and 2, PlexinA4 being the latest member of the PlexinA subfamily to be identified. Little is known about the cellular distribution of PlexinA4 in the spinal cord and dorsal root ganglion (DRG). Here, immunohistochemical studies using antibodies to PlexinA4 revealed immunolabeling in neurons in both dorsal and, to a greater extent, ventral horns of the spinal cord. Ventral horn PlexinA4 positive neurons exhibited morphology, size, and location consistent with both motor neurons and interneurons. Labeling was found in motor axons exiting through the ventral roots, and more widespread labeling was observed in ascending and descending white matter tracts. Within the DRG, immunostaining was observed in neuronal cell bodies as well as the central and peripheral processes of these cells. PlexinA4 is expressed in the peripheral nervous system where its expression is regulated upon nerve injury. This is the first detailed description of the cellular and subcellular distribution of PlexinA4 in the adult spinal cord and DRG, and it will set the basis for future studies on the potential role of PlexinA4 in regeneration and repair of the adult central and peripheral nervous system.

TACE (ADAM17) inhibits Schwann cell myelination.

Tumor necrosis factor-α-converting enzyme (TACE; also known as ADAM17) is a proteolytic sheddase that is responsible for the cleavage of several membrane-bound molecules. We report that TACE cleaves neuregulin-1 (NRG1) type III in the epidermal growth factor domain, probably inactivating it (as assessed by deficient activation of the phosphatidylinositol-3-OH kinase pathway), and thereby negatively regulating peripheral nervous system (PNS) myelination. Lentivirus-mediated knockdown of TACE in vitro in dorsal root ganglia neurons accelerates the onset of myelination and results in hypermyelination. In agreement, motor neurons of conditional knockout mice lacking TACE specifically in these cells are significantly hypermyelinated, and small-caliber fibers are aberrantly myelinated. Further, reduced TACE activity rescues hypomyelination in NRG1 type III haploinsufficient mice in vivo. We also show that the inhibitory effect of TACE is neuron-autonomous, as Schwann cells lacking TACE elaborate myelin of normal thickness. Thus, TACE is a modulator of NRG1 type III activity and is a negative regulator of myelination in the PNS.

Adhesion molecule L1 overexpressed under the control of the neuronal Thy-1 promoter improves myelination after peripheral nerve injury in adult mice.

L1 is an adhesion molecule favorably influencing the functional and anatomical recoveries after central nervous system (CNS) injuries. Its roles in peripheral nervous system (PNS) regeneration are less well understood. Studies using knockout mice have surprisingly revealed that L1 has a negative impact on functional nerve regeneration by inhibiting Schwann cell proliferation. To further elucidate the roles of L1 in PNS regeneration, here we used a novel transgenic mouse overexpressing L1 in neurons, but not in PNS or CNS glial cells, under the control of a neuron-specific Thy-1 promoter. Without nerve injury, the transgene expression, as compared to wild-type mice, had no effect on femoral nerve function, numbers of quadriceps motoneurons and myelinated axons in the femoral nerve but resulted in slightly reduced myelination in the sensory saphenous nerve and increased neurofilament density in myelinated axons of the quadriceps motor nerve branch. After femoral nerve injury, L1 overexpression had no impact on the time course and degree of functional recovery. Unaffected were also numbers of regenerated quadriceps motoneurons, precision of muscle reinnervation, axon numbers and internodal lengths in the regenerated nerves. Despite the lack of functional effects, myelination in the motor and sensory femoral nerve branches was significantly improved and loss of perisomatic inhibitory terminals on motoneurons was attenuated in the transgenic mice. Our results indicate that L1 is a regulator of myelination in the injured PNS and warrant studies aiming to improve function in demyelinating PNS and CNS disorders using exogenous L1.

Spinal opioid receptor-sensitive muscle afferents contribute to the fatigue-induced increase in intracortical inhibition in healthy humans.

We investigated the influence of spinal opioid receptor-sensitive muscle afferents on cortical changes following fatiguing unilateral knee-extensor exercise. On separate days, seven subjects performed an identical five sets of intermittent isometric right-quadriceps contractions, each consisting of eight submaximal contractions [63 ± 7% maximal voluntary contraction (MVC)] and one MVC. The exercise was performed following either lumbar interspinous saline injection or lumbar intrathecal fentanyl injection blocking the central projection of spinal opioid receptor-sensitive lower limb muscle afferents. To quantify exercise-induced peripheral fatigue, quadriceps twitch force (Q(tw,pot)) was assessed via supramaximal magnetic femoral nerve stimulation before and after exercise. Motor evoked potentials and cortical silent periods (CSPs) were evaluated via transcranial magnetic stimulation of the motor cortex during a 3% MVC pre-activation period immediately following exercise. End-exercise quadriceps fatigue was significant and similar in both conditions (Q(tw,pot) -35 and -39% for placebo and fentanyl, respectively; P = 0.38). Immediately following exercise on both days, motor evoked potentials were similar to those obtained prior to exercise. Compared with pre-exercise baseline, CSP in the placebo trial was 21 ± 5% longer postexercise (P < 0.01). In contrast, CSP following the fentanyl trial was not significantly prolonged compared with the pre-exercise baseline (6 ± 4%). Our findings suggest that the central effects of spinal opioid receptor-sensitive muscle afferents might facilitate the fatigue-induced increase in CSP. Furthermore, since the CSP is thought to reflect inhibitory intracortical interneuron activity, which may contribute to central fatigue, our findings imply that spinal opioid receptor-sensitive muscle afferents might influence central fatigue by facilitating intracortical inhibition.