Transplantation of Embryonic Spinal Cord Derived Cells Helps to Prevent Muscle Atrophy after Peripheral Nerve Injury

PubMed Central

Ruven, Carolin; Li, Wen; Li, Heng; Wong, Wai-Man; Wu, Wutian

2017-01-01

Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200–300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy. PMID:28264437

[Improvement in quality of life and exercise capacity without muscular biology changes after general training in patients with severe chronic obstructive pulmonary disease].

PubMed

Pascual-Guardia, Sergio; Wodja, Emil; Gorostiza, Amaya; López de Santamaría, Elena; Gea, Joaquim; Gáldiz, Juan B; Sliwinski, Pawel; Barreiro, Esther

2013-03-02

Despite the beneficial effects of exercise training in chronic obstructive pulmonary disease (COPD) patients, several studies have revealed functional and biological abnormalities in their peripheral muscles. The objective was to determine whether exercise training of high intensity and long duration modifies oxidative stress levels and structure of respiratory and peripheral muscles of severe COPD patients, while also improving their exercise capacity and quality of life. Multicenter study (Warsaw and Barakaldo) in which 25 severe COPD out-patients were recruited from the COPD clinics. In all patients, lung and muscle functions, exercise capacity (walking test and cycloergometer) and quality of life (QoL) were assessed, and open muscle biopsies from the vastus lateralis and external intercostals (n=14) were obtained before and after an exercise training program of high intensity (respiratory rehabilitation area, 70% maximal tolerated load in a cycloergometer) and long duration (10 weeks). Oxidative stress and muscle structural modifications were evaluated in all muscle biopsies using immunoblotting and immunohistochemistry. In all patients, after the training program, without any drop-outs, exercise capacity and QoL improved significantly, whereas oxidative stress, muscle damage and structure were not modified in their respiratory or limb muscles compared to baseline. In patients with severe COPD, exercise training of high intensity and long duration significantly improves their exercise capacity and QoL, without inducing significant modifications on oxidative stress levels or muscle structure in their respiratory or peripheral muscles. These results may have future clinical therapeutic implications. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Hypotonia

MedlinePlus

... will include a detailed examination of the nervous system and muscle function. In most cases, a neurologist (specialist in ... require ongoing care and support. Alternative Names Decreased muscle tone; Floppy infant ... Central nervous system and peripheral nervous system References Burnette WB. Hypotonic ( ...

Aspects of respiratory muscle fatigue in a mountain ultramarathon race.

PubMed

Wüthrich, Thomas U; Marty, Julia; Kerherve, Hugo; Millet, Guillaume Y; Verges, Samuel; Spengler, Christina M

2015-03-01

Ultramarathon running offers a unique possibility to investigate the mechanisms contributing to the limitation of endurance performance. Investigations of locomotor muscle fatigue show that central fatigue is a major contributor to the loss of strength in the lower limbs after an ultramarathon. In addition, respiratory muscle fatigue is known to limit exercise performance, but only limited data are available on changes in respiratory muscle function after ultramarathon running and it is not known whether the observed impairment is caused by peripheral and/or central fatigue. In 22 experienced ultra-trail runners, we assessed respiratory muscle strength, i.e., maximal voluntary inspiratory and expiratory pressures, mouth twitch pressure (n = 16), and voluntary activation (n = 16) using cervical magnetic stimulation, lung function, and maximal voluntary ventilation before and after a 110-km mountain ultramarathon with 5862 m of positive elevation gain. Both maximal voluntary inspiratory (-16% ± 13%) and expiratory pressures (-21% ± 14%) were significantly reduced after the race. Fatigue of inspiratory muscles likely resulted from substantial peripheral fatigue (reduction in mouth twitch pressure, -19% ± 15%; P < 0.01), as voluntary activation (-3% ± 6%, P = 0.09) only tended to be decreased, suggesting negligible or only mild levels of central fatigue. Forced vital capacity remained unchanged, whereas forced expiratory volume in 1 s, peak inspiratory and expiratory flow rates, and maximal voluntary ventilation were significantly reduced (P < 0.05). Ultraendurance running reduces respiratory muscle strength for inspiratory muscles shown to result from significant peripheral muscle fatigue with only little contribution of central fatigue. This is in contrast to findings in locomotor muscles. Whether this difference between muscle groups results from inherent neuromuscular differences, their specific pattern of loading or other reasons remain to be clarified.

Skeletal muscle proteomic signature and metabolic impairment in pulmonary hypertension.

PubMed

Malenfant, Simon; Potus, François; Fournier, Frédéric; Breuils-Bonnet, Sandra; Pflieger, Aude; Bourassa, Sylvie; Tremblay, Ève; Nehmé, Benjamin; Droit, Arnaud; Bonnet, Sébastien; Provencher, Steeve

2015-05-01

Exercise limitation comes from a close interaction between cardiovascular and skeletal muscle impairments. To better understand the implication of possible peripheral oxidative metabolism dysfunction, we studied the proteomic signature of skeletal muscle in pulmonary arterial hypertension (PAH). Eight idiopathic PAH patients and eight matched healthy sedentary subjects were evaluated for exercise capacity, skeletal muscle proteomic profile, metabolism, and mitochondrial function. Skeletal muscle proteins were extracted, and fractioned peptides were tagged using an iTRAQ protocol. Proteomic analyses have documented a total of 9 downregulated proteins in PAH skeletal muscles and 10 upregulated proteins compared to healthy subjects. Most of the downregulated proteins were related to mitochondrial structure and function. Focusing on skeletal muscle metabolism and mitochondrial health, PAH patients presented a decreased expression of oxidative enzymes (pyruvate dehydrogenase, p < 0.01) and an increased expression of glycolytic enzymes (lactate dehydrogenase activity, p < 0.05). These findings were supported by abnormal mitochondrial morphology on electronic microscopy, lower citrate synthase activity (p < 0.01) and lower expression of the transcription factor A of the mitochondria (p < 0.05), confirming a more glycolytic metabolism in PAH skeletal muscles. We provide evidences that impaired mitochondrial and metabolic functions found in the lungs and the right ventricle are also present in skeletal muscles of patients. • Proteomic and metabolic analysis show abnormal oxidative metabolism in PAH skeletal muscle. • EM of PAH patients reveals abnormal mitochondrial structure and distribution. • Abnormal mitochondrial health and function contribute to exercise impairments of PAH. • PAH may be considered a vascular affliction of heart and lungs with major impact on peripheral muscles.

A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.

PubMed

Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N

2016-04-01

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

Neuropathic Pain-like Alterations in Muscle Nociceptor Function Associated with Vibration-induced Muscle Pain

PubMed Central

Chen, Xiaojie; Green, Paul G.; Levine, Jon D.

2010-01-01

We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ~15% of nociceptors demonstrated an intense and long-lasting barrage of action potentials in response to sustained suprathreshold mechanical stimulation (average of 2635 action potentials with frequency of ~44 Hz during a 1 minute suprathreshold stimulus) much greater than has been reported to be produced even by potent inflammatory mediators. While these high-firing nociceptors had lower mechanical thresholds than the remaining nociceptors, exposure to vibration had no effect on conduction velocity and did not induce spontaneous activity. Hyperactivity was not observed in any of 19 neurons from vibration exposed rats pretreated with intrathecal antisense for the IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves, and IL-6 has been implicated in painful peripheral neuropathies, we suggest that the dramatic change in sensory neuron function and development of muscles pain, induced by exposure to vibration, reflects a neuropathic muscle pain syndrome. PMID:20800357

Aryl Hydrocarbon Receptor Nuclear Translocator in Vascular Smooth Muscle Cells Is Required for Optimal Peripheral Perfusion Recovery.

PubMed

Borton, Anna Henry; Benson, Bryan L; Neilson, Lee E; Saunders, Ashley; Alaiti, M Amer; Huang, Alex Y; Jain, Mukesh K; Proweller, Aaron; Ramirez-Bergeron, Diana L

2018-06-01

Limb ischemia resulting from peripheral vascular disease is a common cause of morbidity. Vessel occlusion limits blood flow, creating a hypoxic environment that damages distal tissue, requiring therapeutic revascularization. Hypoxia-inducible factors (HIFs) are key transcriptional regulators of hypoxic vascular responses, including angiogenesis and arteriogenesis. Despite vascular smooth muscle cells' (VSMCs') importance in vessel integrity, little is known about their functional responses to hypoxia in peripheral vascular disease. This study investigated the role of VSMC HIF in mediating peripheral ischemic responses. We used Arnt SMKO mice with smooth muscle-specific deletion of aryl hydrocarbon receptor nuclear translocator (ARNT, HIF-1β), required for HIF transcriptional activity, in a femoral artery ligation model of peripheral vascular disease. Arnt SMKO mice exhibit impaired perfusion recovery despite normal collateral vessel dilation and angiogenic capillary responses. Decreased blood flow manifests in extensive tissue damage and hypoxia in ligated limbs of Arnt SMKO mice. Furthermore, loss of aryl hydrocarbon receptor nuclear translocator changes the proliferation, migration, and transcriptional profile of cultured VSMCs. Arnt SMKO mice display disrupted VSMC morphologic features and wrapping around arterioles and increased vascular permeability linked to decreased local blood flow. Our data demonstrate that traditional vascular remodeling responses are insufficient to provide robust peripheral tissue reperfusion in Arnt SMKO mice. In all, this study highlights HIF responses to hypoxia in arteriole VSMCs critical for the phenotypic and functional stability of vessels that aid in the recovery of blood flow in ischemic peripheral tissues. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Axonal regeneration through acellular muscle grafts

PubMed Central

HALL, SUSAN

1997-01-01

The management of peripheral nerve injury remains a major clinical problem. Progress in this field will almost certainly depend upon manipulating the pathophysiological processes which are triggered by traumatic injuries. One of the most important determinants of functional outcome after the reconstruction of a transected peripheral nerve is the length of the gap between proximal and distal nerve stumps. Long defects (> 2 cm) must be bridged by a suitable conduit in order to support axonal regrowth. This review examines the cellular and acellular elements which facilitate axonal regrowth and the use of acellular muscle grafts in the repair of injuries in the peripheral nervous system. PMID:9034882

Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Lei; Liu, Yi; Zhao, Hua

Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediatedmore » transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a promising strategy for peripheral nerve repair.« less

The development of peripheral fatigue and short-term recovery during self-paced high-intensity exercise

PubMed Central

Froyd, Christian; Millet, Guillaume Y; Noakes, Timothy D

2013-01-01

The time course of muscular fatigue that develops during and after an intense bout of self-paced dynamic exercise was characterized by using different forms of electrical stimulation (ES) of the exercising muscles. Ten active subjects performed a time trial (TT) involving repetitive concentric extension/flexion of the right knee using a Biodex dynamometer. Neuromuscular function (NMF), including ES and a 5 s maximal isometric voluntary contraction (MVC), was assessed before the start of the TT and immediately (<5 s) after each 20% of the TT had been completed, as well as 1, 2, 4 and 8 min after TT termination. The TT time was 347 ± 98 s. MVCs were 52% of baseline values at TT termination. Torque responses from ES were reduced to 33–68% of baseline using different methods of stimulation, suggesting that the extent to which peripheral fatigue is documented during exercise depends upon NMF assessment methodology. The major changes in muscle function occurred within the first 40% of exercise. Significant recovery in skeletal muscle function occurs within the first 1–2 min after exercise, showing that previous studies may have underestimated the extent to which peripheral fatigue develops during exercise. PMID:23230235

Electrically stimulated signals from a long-term Regenerative Peripheral Nerve Interface.

PubMed

Langhals, Nicholas B; Woo, Shoshana L; Moon, Jana D; Larson, John V; Leach, Michelle K; Cederna, Paul S; Urbanchek, Melanie G

2014-01-01

Despite modern technological advances, the most widely available prostheses provide little functional recovery beyond basic grasping. Although sophisticated upper extremity prostheses are available, optimal prosthetic interfaces which give patients high-fidelity control of these artificial limbs are limited. We have developed a novel Regenerative Peripheral Nerve Interface (RPNI), which consists of a unit of free muscle that has been neurotized by a transected peripheral nerve. In conjunction with a biocompatible electrode on the muscle surface, the RPNI facilitates signal transduction from a residual peripheral nerve to a neuroprosthetic limb. The purpose of this study was to explore signal quality and reliability in an RPNI following an extended period of implantation. Following a 14-month maturation period, electromyographic signal generation was evaluated via electrical stimulation of the innervating nerve. The long-term RPNI was viable and healthy, as demonstrated by evoked compound muscle action potentials as well as histological tissue analysis. Signals exceeding 4 mV were successfully acquired and amplitudes were consistent across multiple repetitions of applied stimuli. There were no evident signs of muscle denervation, significant scar tissue, or muscle necrosis. This study provides further evidence that after a maturation period exceeding 1 year, reliable and consistent signals can still be acquired from an RPNI.

Reduced Radial Displacement of the Gastrocnemius Medialis Muscle After Electrically Elicited Fatigue.

PubMed

Macgregor, Lewis J; Ditroilo, Massimiliano; Smith, Iain J; Fairweather, Malcolm M; Hunter, Angus M

2016-08-01

Assessments of skeletal-muscle functional capacity often necessitate maximal contractile effort, which exacerbates muscle fatigue or injury. Tensiomyography (TMG) has been investigated as a means to assess muscle contractile function after fatigue; however, observations have not been contextualized by concurrent physiological measures. To measure peripheral-fatigue-induced alterations in mechanical and contractile properties of the plantar-flexor muscles through noninvasive TMG concurrently with maximal voluntary contraction (MVC) and passive muscle tension (PMT) to validate TMG as a gauge of peripheral fatigue. Pre- and posttest intervention with control. University laboratory. 21 healthy male volunteers. Subjects' plantar flexors were tested for TMG parameters, along with MVC and PMT, before and after either a 5-min rest period (control) or a 5-min electrical-stimulation intervention (fatigue). Temporal (contraction velocity) and spatial (radial displacement) contractile parameters of the gastrocnemius medialis were recorded through TMG. MVC was measured as an indicator of muscle fatigue, and PMT was measured to assess muscle stiffness. Radial displacement demonstrated a fatigue-associated reduction (3.3 ± 1.2 vs 4.0 ± 1.4 mm, P = .031), while contraction velocity remained unaltered. In addition, MVC significantly declined by 122.6 ± 104 N (P < .001) after stimulation (fatigue). PMT was significantly increased after fatigue (139.8 ± 54.3 vs 111.3 ± 44.6 N, P = .007). TMG successfully detected fatigue, evident from reduced MVC, by displaying impaired muscle displacement accompanied by elevated PMT. TMG could be useful in establishing skeletal-muscle fatigue status without exacerbating the functional decrement of the muscle.

Optogenetic probing of nerve and muscle function after facial nerve lesion in the mouse whisker system

NASA Astrophysics Data System (ADS)

Bandi, Akhil; Vajtay, Thomas J.; Upadhyay, Aman; Yiantsos, S. Olga; Lee, Christian R.; Margolis, David J.

2018-02-01

Optogenetic modulation of neural circuits has opened new avenues into neuroscience research, allowing the control of cellular activity of genetically specified cell types. Optogenetics is still underdeveloped in the peripheral nervous system, yet there are many applications related to sensorimotor function, pain and nerve injury that would be of great benefit. We recently established a method for non-invasive, transdermal optogenetic stimulation of the facial muscles that control whisker movements in mice (Park et al., 2016, eLife, e14140)1. Here we present results comparing the effects of optogenetic stimulation of whisker movements in mice that express channelrhodopsin-2 (ChR2) selectively in either the facial motor nerve (ChAT-ChR2 mice) or muscle (Emx1-ChR2 or ACTA1-ChR2 mice). We tracked changes in nerve and muscle function before and up to 14 days after nerve transection. Optogenetic 460 nm transdermal stimulation of the distal cut nerve showed that nerve degeneration progresses rapidly over 24 hours. In contrast, the whisker movements evoked by optogenetic muscle stimulation were up-regulated after denervation, including increased maximum protraction amplitude, increased sensitivity to low-intensity stimuli, and more sustained muscle contractions (reduced adaptation). Our results indicate that peripheral optogenetic stimulation is a promising technique for probing the timecourse of functional changes of both nerve and muscle, and holds potential for restoring movement after paralysis induced by nerve damage or motoneuron degeneration.

[THE CHANGES OF NOCICEPTIVE THRESHOLD AND ACTIVITY OF THE ADENYLYL CYCLASE SYSTEM IN THE SKELETAL MUSCLES OF RATS WITH ACUTE AND MILD TYPE 1 DIABETES MELLITUS ].

PubMed

Shipilov, V N; Trost, A M; Chistyakova, O V; Derkach, K V; Shpakov, A O

2016-02-01

Diabetic peripheral neuropathy (DPN) is one of the most common complications of the type 1 diabetes mellitus (DM1). The aim of the work was to study the dynamics of a painful DPN and functional state of the hormone-sensitive ACSS in the skeletal muscles of rats with the models of acute and mild DM1, as well as the study of impact on them of insulin therapy with different ways of hormone delivery - intranasal and peripheral. In both models of DM1, the level of nociceptive threshold in rats decreased and the stimulatory effects of guanine nucleotides (GppNHp) and adrenergic agonists (isoproterenol, BRL-37344) on adenylyl cyclase (AC) activity were attenuated. The AC stimulating effect of relaxin decreased in animals with acute DM1, but in mild DM1, the decrease was insignificant. Peripheral administration of insulin in rats with acute DM1 increased the nociceptive threshold and partially restored the AC effect of ß 3-agonist BRL-37344. Intranasal administration of insulin in rats with DM1 also increased the nociceptive threshold and partially restored the basal and BRL-37344-stimulated AC activity in the skeletal muscles of diabetic animals. Thus, in the skeletal muscles of rats with acute and mild DM1 the nociceptive sensitivity and the functions of ACSS were disturbed, and they were partially restored by the treatment with peripheral (acute DM1) or intranasal (mild DM1) insulin.

Impaired muscle efficiency but preserved peripheral hemodynamics and mitochondrial function with advancing age: Evidence from exercise in the young, old, and oldest-old.

PubMed

Layec, Gwenael; Trinity, Joel D; Hart, Corey R; Le Fur, Yann; Zhao, Jia; Reese, Van; Jeong, Eun-Kee; Richardson, Russell S

2018-03-23

Muscle weakness in the elderly has been linked to recurrent falls and morbidity, therefore, elucidating the mechanisms contributing to the loss of muscle function and mobility with advancing age is critical. To this aim, we comprehensively examined skeletal muscle metabolic function and hemodynamics in 11 young (23±2 yrs), 11 old (68±2 yrs), and 10 oldest-old (84±2 yrs) physical activity-matched subjects. Specifically, oxidative stress markers, mitochondrial function and the ATP cost of contraction as well as peripheral hemodynamics were assessed during dynamic plantar flexion exercise at 40% of maximal work rate (WRmax). Both the PCr recovery time constant and the peak rate of mitochondrial ATP synthesis were not significantly different between groups. In contrast, the ATP cost of dynamic contractions (young: 1.5±1.0, old: 3.4±2.1, oldest-old: 6.1±3.6 mM.min-1.W-1) and systemic markers of oxidative stress were signficantly increased with age, with the ATP cost of contraction being negatively correlated with WRmax (r=0.59, P<0.05). End-of-exercise blood flow per Watt rose significantly with increasing age (young: 37±20, old: 82±68, oldest-old: 154±93 ml.min-1.W-1). These findings suggest that the progressive deterioration of muscle contractile efficiency with advancing age may play an important role in the decline in skeletal muscle functional capacity in the elderly.

Neurologic examination and instrument-based measurements in the evaluation of ulnar neuropathy at the elbow.

PubMed

Omejec, Gregor; Podnar, Simon

2018-06-01

The aim of the study was to compare the utility of instrument-based assessment of peripheral nerve function with the neurologic examination in ulnar neuropathy at the elbow (UNE). We prospectively recruited consecutive patients with suspected UNE, performed a neurologic examination, and performed instrument-based measurements (muscle cross-sectional area by ultrasonography, muscle strength by dynamometry, and sensation using monofilaments). We found good correlations between clinical estimates and corresponding instrument-based measurements, with similar ability to diagnose UNE and predict UNE pathophysiology. Although instrument-based methods provide quantitative evaluation of peripheral nerve function, we did not find them to be more sensitive or specific in the diagnosis of UNE than the standard neurologic examination. Likewise, instrument-based methods were not better able to differentiate between groups of UNE patients with different pathophysiologies. Muscle Nerve 57: 951-957, 2018. © 2017 Wiley Periodicals, Inc.

X-ray irradiation has positive effects for the recovery of peripheral nerve injury maybe through the vascular smooth muscle contraction signaling pathway.

PubMed

Jiang, Bo; Zhang, Yong; She, Chang; Zhao, Jiaju; Zhou, Kailong; Zuo, Zhicheng; Zhou, Xiaozhong; Wang, Peiji; Dong, Qirong

2017-09-01

It is well known that moderate to high doses of ionizing radiation have a toxic effect on the organism. However, there are few experimental studies on the mechanisms of LDR ionizing radiation on nerve regeneration after peripheral nerve injury. We established the rats' peripheral nerve injury model via repaired Peripheral nerve injury nerve, vascular endothelial growth factor a and Growth associated protein-43 were detected from different treatment groups. We performed transcriptome sequencing focusing on investigating the differentially expressed genes and gene functions between the control group and 1Gy group. Sequencing was done by using high-throughput RNA-sequencing (RNA-seq) technologies. The results showed the 1Gy group to be the most effective promoting repair. RNA-sequencing identified 619 differently expressed genes between control and treated groups. A Gene Ontology analysis of the differentially expressed genes revealed enrichment in the functional pathways. Among them, candidate genes associated with nerve repair were identified. Pathways involved in cell-substrate adhesion, vascular smooth muscle contraction and cell adhesion molecule signaling may be involved in recovery from peripheral nerve injury. Copyright © 2017. Published by Elsevier B.V.

Primary Motor Cortex Representation of Handgrip Muscles in Patients with Leprosy

PubMed Central

Rangel, Maria Luíza Sales; Sanchez, Tiago Arruda; Moreira, Filipe Azaline; Hoefle, Sebastian; Souto, Inaiacy Bittencourt; da Cunha, Antônio José Ledo Alves

2015-01-01

Background Leprosy is an endemic infectious disease caused by Mycobacterium leprae that predominantly attacks the skin and peripheral nerves, leading to progressive impairment of motor, sensory and autonomic function. Little is known about how this peripheral neuropathy affects corticospinal excitability of handgrip muscles. Our purpose was to explore the motor cortex organization after progressive peripheral nerve injury and upper-limb dysfunction induced by leprosy using noninvasive transcranial magnetic stimulation (TMS). Methods In a cross-sectional study design, we mapped bilaterally in the primary motor cortex (M1) the representations of the hand flexor digitorum superficialis (FDS), as well as of the intrinsic hand muscles abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM). All participants underwent clinical assessment, handgrip dynamometry and motor and sensory nerve conduction exams 30 days before mapping. Wilcoxon signed rank and Mann-Whitney tests were performed with an alpha-value of p<0.05. Findings Dynamometry performance of the patients’ most affected hand (MAH), was worse than that of the less affected hand (LAH) and of healthy controls participants (p = 0.031), confirming handgrip impairment. Motor threshold (MT) of the FDS muscle was higher in both hemispheres in patients as compared to controls, and lower in the hemisphere contralateral to the MAH when compared to that of the LAH. Moreover, motor evoked potential (MEP) amplitudes collected in the FDS of the MAH were higher in comparison to those of controls. Strikingly, MEPs in the intrinsic hand muscle FDI had lower amplitudes in the hemisphere contralateral to MAH as compared to those of the LAH and the control group. Taken together, these results are suggestive of a more robust representation of an extrinsic hand flexor and impaired intrinsic hand muscle function in the hemisphere contralateral to the MAH due to leprosy. Conclusion Decreased sensory-motor function induced by leprosy affects handgrip muscle representation in M1. PMID:26203653

The Role of Genetically Modified Mesenchymal Stem Cells in Urinary Bladder Regeneration.

PubMed

Snow-Lisy, Devon C; Diaz, Edward C; Bury, Matthew I; Fuller, Natalie J; Hannick, Jessica H; Ahmad, Nida; Sharma, Arun K

2015-01-01

Recent studies have demonstrated that mesenchymal stem cells (MSCs) combined with CD34+ hematopoietic/stem progenitor cells (HSPCs) can function as surrogate urinary bladder cells to synergistically promote multi-faceted bladder tissue regeneration. However, the molecular pathways governing these events are unknown. The pleiotropic effects of Wnt5a and Cyr61 are known to affect aspects of hematopoiesis, angiogenesis, and muscle and nerve regeneration. Within this study, the effects of Cyr61 and Wnt5a on bladder tissue regeneration were evaluated by grafting scaffolds containing modified human bone marrow derived MSCs. These cell lines were engineered to independently over-express Wnt5a or Cyr61, or to exhibit reduced expression of Cyr61 within the context of a nude rat bladder augmentation model. At 4 weeks post-surgery, data demonstrated increased vessel number (~250 vs ~109 vessels/mm2) and bladder smooth muscle content (~42% vs ~36%) in Cyr61OX (over-expressing) vs Cyr61KD (knock-down) groups. Muscle content decreased to ~25% at 10 weeks in Cyr61KD groups. Wnt5aOX resulted in high numbers of vessels and muscle content (~206 vessels/mm2 and ~51%, respectively) at 4 weeks. Over-expressing cell constructs resulted in peripheral nerve regeneration while Cyr61KD animals were devoid of peripheral nerve regeneration at 4 weeks. At 10 weeks post-grafting, peripheral nerve regeneration was at a minimal level for both Cyr61OX and Wnt5aOX cell lines. Blood vessel and bladder functionality were evident at both time-points in all animals. Results from this study indicate that MSC-based Cyr61OX and Wnt5aOX cell lines play pivotal roles with regards to increasing the levels of functional vasculature, influencing muscle regeneration, and the regeneration of peripheral nerves in a model of bladder augmentation. Wnt5aOX constructs closely approximated the outcomes previously observed with the co-transplantation of MSCs with CD34+ HSPCs and may be specifically targeted as an alternate means to achieve functional bladder regeneration.

The Role of Parvalbumin, Sarcoplasmatic Reticulum Calcium Pump Rate, Rates of Cross-Bridge Dynamics, and Ryanodine Receptor Calcium Current on Peripheral Muscle Fatigue: A Simulation Study

PubMed Central

Neumann, Verena

2016-01-01

A biophysical model of the excitation-contraction pathway, which has previously been validated for slow-twitch and fast-twitch skeletal muscles, is employed to investigate key biophysical processes leading to peripheral muscle fatigue. Special emphasis hereby is on investigating how the model's original parameter sets can be interpolated such that realistic behaviour with respect to contraction time and fatigue progression can be obtained for a continuous distribution of the model's parameters across the muscle units, as found for the functional properties of muscles. The parameters are divided into 5 groups describing (i) the sarcoplasmatic reticulum calcium pump rate, (ii) the cross-bridge dynamics rates, (iii) the ryanodine receptor calcium current, (iv) the rates of binding of magnesium and calcium ions to parvalbumin and corresponding dissociations, and (v) the remaining processes. The simulations reveal that the first two parameter groups are sensitive to contraction time but not fatigue, the third parameter group affects both considered properties, and the fourth parameter group is only sensitive to fatigue progression. Hence, within the scope of the underlying model, further experimental studies should investigate parvalbumin dynamics and the ryanodine receptor calcium current to enhance the understanding of peripheral muscle fatigue. PMID:27980606

Mechanisms of physical activity limitation in chronic lung diseases.

PubMed

Vogiatzis, Ioannis; Zakynthinos, George; Andrianopoulos, Vasileios

2012-01-01

In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i) the imbalance between ventilatory capacity and demand, (ii) the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii) the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea) and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients' quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy.

MRI abnormalities of peripheral nerve and muscle are common in amyotrophic lateral sclerosis and share features with multifocal motor neuropathy

PubMed Central

Staff, Nathan P.; Amrami, Kimberly K.; Howe, Benjamin M.

2015-01-01

Introduction MRI of peripheral nerve and muscle in patients with ALS may be performed to investigate alternative diagnoses including multifocal motor neuropathy (MMN). MRI findings of peripheral nerve and muscle are not well described in these conditions, making interpretation of results difficult. Methods We examined systematically the peripheral nerve and muscle MRI findings in patients with ALS (n=60) and MMN (n=8). Results In patients with ALS and MMN, abnormal MRIs were common (85% and 75%, respectively) but did not correlate with disease severity. Peripheral nerve MRI abnormalities were similar in frequency (ALS: 58% vs. MMN: 63%) with most changes being of mild-to-moderate severity. Muscle MRI changes were more common in ALS (57% vs. 33%), and no muscle atrophy was seen in patients with MMN. Discussion MRI abnormalities of peripheral nerve and muscle in ALS and MMN are common and share some features. PMID:25736373

Postural steadiness and ankle force variability in peripheral neuropathy

PubMed Central

Paxton, Roger J.; Feldman-Kothe, Caitlin; Trabert, Megan K.; Hitchcock, Leah N.; Reiser, Raoul F.; Tracy, Brian L.

2015-01-01

Introduction The purpose was to determine the effect of peripheral neuropathy (PN) on motor output variability for ankle muscles of older adults, and the relation between ankle motor variability and postural stability in PN patients. Methods Older adults with (O-PN) and without PN (O), and young adults (Y) underwent assessment of standing postural stability and ankle muscle force steadiness. Results O-PN displayed impaired ankle muscle force control and postural stability compared with O and Y groups. For O-PN, the amplitude of plantarflexor force fluctuations was moderately correlated with postural stability under no-vision conditions (r = 0.54, P = 0.01). Discussion The correlation of variations in ankle force with postural stability in PN suggests a contribution of ankle muscle dyscontrol to the postural instability that impacts physical function for older adults with PN. PMID:26284897

Muscle function in COPD: a complex interplay

PubMed Central

Donaldson, Anna V; Maddocks, Matthew; Martolini, Dario; Polkey, Michael I; Man, William D-C

2012-01-01

The skeletal muscles play an essential role in life, providing the mechanical basis for respiration and movement. Skeletal muscle dysfunction is prevalent in all stages of chronic obstructive pulmonary disease (COPD), and significantly influences symptoms, functional capacity, health related quality of life, health resource usage and even mortality. Furthermore, in contrast to the lungs, the skeletal muscles are potentially remedial with existing therapy, namely exercise-training. This review summarizes clinical and laboratory observations of the respiratory and peripheral skeletal muscles (in particular the diaphragm and quadriceps), and current understanding of the underlying etiological processes. As further progress is made in the elucidation of the molecular mechanisms of skeletal muscle dysfunction, new pharmacological therapies are likely to emerge to treat this important extra-pulmonary manifestation of COPD. PMID:22973093

Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men.

PubMed

Brøns, Charlotte; Jensen, Christine B; Storgaard, Heidi; Hiscock, Natalie J; White, Andrew; Appel, Julie S; Jacobsen, Stine; Nilsson, Emma; Larsen, Claus M; Astrup, Arne; Quistorff, Bjørn; Vaag, Allan

2009-05-15

A high-fat, high-calorie diet is associated with obesity and type 2 diabetes. However, the relative contribution of metabolic defects to the development of hyperglycaemia and type 2 diabetes is controversial. Accumulation of excess fat in muscle and adipose tissue in insulin resistance and type 2 diabetes may be linked with defective mitochondrial oxidative phosphorylation. The aim of the current study was to investigate acute effects of short-term fat overfeeding on glucose and insulin metabolism in young men. We studied the effects of 5 days' high-fat (60% energy) overfeeding (+50%) versus a control diet on hepatic and peripheral insulin action by a hyperinsulinaemic euglycaemic clamp, muscle mitochondrial function by (31)P magnetic resonance spectroscopy, and gene expression by qrt-PCR and microarray in 26 young men. Hepatic glucose production and fasting glucose levels increased significantly in response to overfeeding. However, peripheral insulin action, muscle mitochondrial function, and general and specific oxidative phosphorylation gene expression were unaffected by high-fat feeding. Insulin secretion increased appropriately to compensate for hepatic, and not for peripheral, insulin resistance. High-fat feeding increased fasting levels of plasma adiponectin, leptin and gastric inhibitory peptide (GIP). High-fat overfeeding increases fasting glucose levels due to increased hepatic glucose production. The increased insulin secretion may compensate for hepatic insulin resistance possibly mediated by elevated GIP secretion. Increased insulin secretion precedes the development of peripheral insulin resistance, mitochondrial dysfunction and obesity in response to overfeeding, suggesting a role for insulin per se as well GIP, in the development of peripheral insulin resistance and obesity.

Immunological Tolerance to Muscle Autoantigens Involves Peripheral Deletion of Autoreactive CD8+ T Cells

PubMed Central

Franck, Emilie; Bonneau, Carole; Jean, Laetitia; Henry, Jean-Paul; Lacoume, Yann; Salvetti, Anna; Boyer, Olivier; Adriouch, Sahil

2012-01-01

Muscle potentially represents the most abundant source of autoantigens of the body and can be targeted by a variety of severe autoimmune diseases. Yet, the mechanisms of immunological tolerance toward muscle autoantigens remain mostly unknown. We investigated this issue in transgenic SM-Ova mice that express an ovalbumin (Ova) neo-autoantigen specifically in skeletal muscle. We previously reported that antigen specific CD4+ T cell are immunologically ignorant to endogenous Ova in this model but can be stimulated upon immunization. In contrast, Ova-specific CD8+ T cells were suspected to be either unresponsive to Ova challenge or functionally defective. We now extend our investigations on the mechanisms governing CD8+ tolerance in SM-Ova mice. We show herein that Ova-specific CD8+ T cells are not detected upon challenge with strongly immunogenic Ova vaccines even after depletion of regulatory T cells. Ova-specific CD8+ T cells from OT-I mice adoptively transferred to SM-Ova mice started to proliferate in vivo, acquired CD69 and PD-1 but subsequently down-regulated Bcl-2 and disappeared from the periphery, suggesting a mechanism of peripheral deletion. Peripheral deletion of endogenous Ova-specific cells was formally demonstrated in chimeric SM-Ova mice engrafted with bone marrow cells containing T cell precursors from OT-I TCR-transgenic mice. Thus, the present findings demonstrate that immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells. PMID:22570714

Respiratory muscle function and exercise limitation in patients with chronic obstructive pulmonary disease: a review.

PubMed

Charususin, Noppawan; Dacha, Sauwaluk; Gosselink, Rik; Decramer, Marc; Von Leupoldt, Andreas; Reijnders, Thomas; Louvaris, Zafeiris; Langer, Daniel

2018-01-01

Respiratory muscle dysfunction is common and contributes to dyspnea and exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Improving dynamic function of respiratory muscles during exercise might help to reduce symptoms and improve exercise capacity. Areas covered: The aims of this review are to 1) summarize physiological mechanisms linking respiratory muscle dysfunction to dyspnea and exercise limitation; 2) provide an overview of available therapeutic approaches to better maintain load-capacity balance of respiratory muscles during exercise; and 3) to summarize current knowledge on potential mechanisms explaining effects of interventions aimed at optimizing dynamic respiratory muscle function with a special focus on inspiratory muscle training. Expert commentary: Several mechanisms which are potentially linking improvements in dynamic respiratory muscle function to symptomatic and functional benefits have not been studied so far in COPD patients. Examples of underexplored areas include the study of neural processes related to the relief of acute dyspnea and the competition between respiratory and peripheral muscles for limited energy supplies during exercise. Novel methodologies are available to non-invasively study these mechanisms. Better insights into the consequences of dynamic respiratory muscle dysfunction will hopefully contribute to further refine and individualize therapeutic approaches in patients with COPD.

Relationship between peripheral muscle structure and function in patients with chronic obstructive pulmonary disease with different nutritional status.

PubMed

Malaguti, Carla; Napolis, Lara M; Villaça, Débora; Neder, José A; Nery, Luiz E; Dal Corso, Simone

2011-07-01

The purpose of this study was to investigate the relationships between peripheral muscle structure (mass) and function (strength, endurance, and maximal aerobic capacity) in patients with chronic obstructive pulmonary disease (COPD) with different nutritional states. Thirty-nine patients (31 male) with moderate-severe COPD (63.5 ± 7.3 [SD] years) and 17 controls (14 male; 64.7 ± 5.5 [SD] years) underwent isokinetic (peak torque [PT]), isometric (isometric torque [IT]), and endurance strength (total work [TW]) measurements of the knee extensor muscles and a maximal cardiopulmonary exercise test to evaluate the maximal aerobic capacity (peak oxygen uptake [VO(2)] peak). Muscle mass (MM) was determined using dual-energy x-ray absorptiometry. Patients with COPD presented with reduced muscle function as compared with the healthy controls: PT (105.9 ± 33.9 vs. 134.3 ± 30.9, N·m(-1), respectively, p < 0.05), TW (1,446.3 ± 550.8 vs. 1,792.9 ± 469.1 kJ, respectively, p < 0.05), and VO(2)peak (68.1 ± 15.1 vs. 93.7 ± 14.5, % pred, respectively, p < 0.05). Significant relationships were found between muscle structure and function (strength and endurance) in the patient subgroup with preserved MM and in the control group: PT·MM(r(2) = 0.36; p = 0.01 vs. r(2) = 0.32; p = 0.01, respectively) and TW·MM (r(2) = 0.32; p = 0.01 vs. r(2) = 0.22; p = 0.05, respectively). Strength corrected for mass normalized this function in both patient subgroups, whereas endurance was normalized only in the patient subgroup without muscle depletion. Maximal aerobic capacity remained reduced, despite the correction, in both patient subgroups (depleted or nondepleted) compared with the healthy controls (VO(2)peak.MM: 9.1 ± 3.7 vs. 21.8 ± 4.9 vs. 28.5 ± 4.2 ml·min·kg, respectively, with p < 0.01 among groups). Muscle atrophy seems to be the main determinant of strength reduction among patients with moderate-severe COPD, whereas endurance reduction seems to be more related to imbalance between oxygen delivery and consumption than to the local muscle structure itself. Peripheral MM did not constitute a good predictor for maximal aerobic capacity in this population. The main practical application of this study is to point out a crucial role for the strategies able to ameliorate cardiorespiratory and muscular fitness in patients with COPD, even in those patients with preserved MM.

Recovery of peripheral muscle function from fatiguing exercise and daily physical activity level in patients with multiple sclerosis: a case-control study.

PubMed

Ickmans, Kelly; Simoens, Fauve; Nijs, Jo; Kos, Daphne; Cras, Patrick; Willekens, Barbara; Meeus, Mira

2014-07-01

Delayed recovery of muscle function following exercise has been demonstrated in the lower limbs of patients with multiple sclerosis (MS). However, studies examining this in the upper limbs are currently lacking. This study compared physical activity level (PAL) and recovery of upper limb muscle function following exercise between MS patients and healthy inactive controls. Furthermore, the relationship between PAL and muscle recovery was examined. PAL of 19 MS patients and 32 controls was measured using an accelerometer for 7 consecutive days. Afterwards, recovery of muscle function was assessed by performing a fatiguing upper limb exercise test with subsequent recovery measures. Muscle recovery of the upper limb muscles was similar in both groups. Average activity counts were significantly lower in MS patients than in the control group. MS patients spent significantly more time being sedentary and less time on activities of moderate intensity compared with the control group. No significant correlation between PAL and recovery of muscle function was found in MS patients. Recovery of upper limb muscle function following exercise is normal in MS patients. MS patients are less physically active than healthy inactive controls. PAL and recovery of upper limb muscle function appear unrelated in MS patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Upslope treadmill exercise enhances motor axon regeneration but not functional recovery following peripheral nerve injury

PubMed Central

Cannoy, Jill; Crowley, Sam; Jarratt, Allen; Werts, Kelly LeFevere; Osborne, Krista; Park, Sohee

2016-01-01

Following peripheral nerve injury, moderate daily exercise conducted on a level treadmill results in enhanced axon regeneration and modest improvements in functional recovery. If the exercise is conducted on an upwardly inclined treadmill, even more motor axons regenerate successfully and reinnervate muscle targets. Whether this increased motor axon regeneration also results in greater improvement in functional recovery from sciatic nerve injury was studied. Axon regeneration and muscle reinnervation were studied in Lewis rats over an 11 wk postinjury period using stimulus evoked electromyographic (EMG) responses in the soleus muscle of awake animals. Motor axon regeneration and muscle reinnervation were enhanced in slope-trained rats. Direct muscle (M) responses reappeared faster in slope-trained animals than in other groups and ultimately were larger than untreated animals. The amplitude of monosynaptic H reflexes recorded from slope-trained rats remained significantly smaller than all other groups of animals for the duration of the study. The restoration of the amplitude and pattern of locomotor EMG activity in soleus and tibialis anterior and of hindblimb kinematics was studied during treadmill walking on different slopes. Slope-trained rats did not recover the ability to modulate the intensity of locomotor EMG activity with slope. Patterned EMG activity in flexor and extensor muscles was not noted in slope-trained rats. Neither hindblimb length nor limb orientation during level, upslope, or downslope walking was restored in slope-trained rats. Slope training enhanced motor axon regeneration but did not improve functional recovery following sciatic nerve transection and repair. PMID:27466130

Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

PubMed

Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

2016-05-27

Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury.

Bridging extra large defects of peripheral nerves: possibilities and limitations of alternative biological grafts from acellular muscle and Schwann cells.

PubMed

Keilhoff, Gerburg; Prätsch, Florian; Wolf, Gerald; Fansa, Hisham

2005-01-01

Defects of peripheral nerves are bridged with autologous nerve grafts. Tissue-engineered nerve grafts offer a laboratory-based alternative to overcome limited donor nerve availability. Our objective was to evaluate whether a graft made from acellular muscle enriched with cultivated Schwann cells can bridge extra large gaps where conventional conduits usually fail. Our well-established rat sciatic nerve model was used with an increased gap length of 50 mm. The conduits consisted of freeze-thawed or chemically extracted homologous acellular rat rectus muscles and implanted Schwann cells. Autologous nerve grafts were used for control purposes. Biocompatibility of the grafts was demonstrated by Schwann cell settlement, revascularization, and macrophage recruitment. After 12 weeks regeneration was assessed clinically, histologically, and morphometrically. The control group showed superior results regarding axon counts, histologic appearance, and functional recovery compared with the muscle grafts. The chemically extracted conduits completely failed to support nerve regeneration. They were not stable enough to bridge longer nerve gaps with an expanded regeneration time. On the basis of morphological parameters freeze-thawed muscle grafts were, however, able to support peripheral nerve regeneration even over the extralong distance of 50 mm, and therefore are of potential benefit for new therapeutic strategies.

Vascular and Skeletal Muscle Function in Gulf War Veterans Illness

DTIC Science & Technology

2016-07-01

Approximately 40% of Gulf War Veterans (over ¼ million Veterans) have GWI by the Center for Disease Control criteria for GWI (a recommended method for defining...for Disease Control and Prevention (CDC)’s clinical diagnostic criteria for GWI is one of two recommended by an Expert Committee, and is based on...other illnesses with muscle fatigue, pain, and abnormal muscle metabolism, such as peripheral artery disease and chronic heart failure, and advance

Peripheral circulatory responses in vivo from regional brachial biceps and lumbar muscles in healthy men and women during pushing and pulling exercise.

PubMed

Maikala, Rammohan V; Bhambhani, Yagesh N

2007-06-01

Although women have been performing increasingly more manual labor in the workplace in the past 2 decades, their physiological responses and gender-based differences in muscle microvascularity during occupational activities have not yet been extensively documented. This study assessed gender differences and tissue heterogeneity in peripheral circulatory responses from 2 muscle groups during pushing and pulling exercise until volitional exhaustion. In healthy men and women, near-infrared spectroscopy was used to determine peripheral responses, oxygenation, and blood volume simultaneously from the right biceps brachii and lumbar erector spinae. Pulmonary oxygen uptake was assessed using a metabolic measurement cart. Although the 11 men who participated in the study demonstrated greater pulmonary oxygen uptake and power output at volitional exhaustion, their peak peripheral responses for both muscles were similar to those of the 11 women participating. In both sexes, oxygenations trends decreased in both muscles with an increase in workload. However, whereas blood volume increased in the biceps, it decreased in the lumbar muscle in both sexes. At 20% to 60% levels of peak pulmonary oxygen uptake, the percent change in peripheral bicep responses was greater for men than for women (P < 0.05). In contrast, women demonstrated greater change in lumbar muscle oxygenation compared with men at 40% to 60% of peak pulmonary oxygen uptake (P < 0.05). Similar peripheral responses for biceps and lumbar muscles at the point of volitional exhaustion suggest that gender differences in pulmonary oxygen uptake are independent of oxygen extraction or delivery across the muscle groups monitored. However, at submaximal levels of exercise, the peripheral changes in each muscle were gender dependent. Although biceps and lumbar muscles are 2 discrete muscle groups, based on the heterogeneity found in the blood volume trends it is likely that oxygen supply and demand are regulated by muscle location and muscle fiber characteristics. Overall, gender-based assessment of occupational activities should incorporate both pulmonary and peripheral circulatory responses to understand each sex's performance effectiveness.

Long-term effect of prednisolone on functional blink recovery after transient peripheral facial motor paralysis.

PubMed

VanderWerf, Frans; Reits, Dik; Metselaar, Mick; De Zeeuw, Chris I

2012-03-01

To determine the functional recovery in patients with severe transient peripheral facial motor paralysis (Bell palsy). Prospective controlled trial. Academic medical center. Blink recovery was studied in 2 groups of severely affected Bell palsy patients during a follow-up period of 84 weeks. The patients in one group received prednisolone within the first week after the onset of symptoms. No medication was given to the other group. A control group of healthy subjects was also included. Simultaneous orbicularis oculi muscle activity and eyelid kinematics were recorded by surface electromyographic (EMG) recording and eyelid search coils, respectively. At the beginning of the paralysis, very little integrated orbicularis oculi muscle activity and eyelid movement was measured at the palsied side of the face. Thirteen weeks later, the integrated orbicularis oculi EMG and functional blink recovery gradually improved until 39 weeks. Beyond, only the integrated orbicularis oculi EMG slightly increased. At 84 weeks, the integrated orbicularis oculi EMG was significantly larger in the prednisolone group compared with the control group. The integrated EMG of the nonmedicated group recovered to normal values. Curiously enough, the functional blink recovery at the palsied side remained reduced to 64% compared with the healthy controls in the prednisolone-treated group and to 36% in the nonmedicated group. The authors demonstrate that prednisolone significantly increased the orbicularis oculi muscle activity and significantly improved functional blink recovery in severely affected Bell palsy patients. However, the increase of muscle activity was insufficient to restore functional blinking to normal values.

Identification of the effects of peripheral nerves injury on the muscle control - A review

NASA Astrophysics Data System (ADS)

Cabaj, Anna; Zmyslowski, Wojciech

2011-01-01

Impairment of motor function following peripheral nerve injury is a serious clinical problem. Generally nerve injury leads to erroneous control of muscle activity that results in gait and voluntary movement abnormalities followed by muscle atrophy. This article presents a review of studies on the effects of peripheral nerve injury on the motor system performed on animal models. We focused our attention on the results that are fundamental for better understanding of the degenerative and regenerative processes induced by nerve injury as well as of the mechanisms of structural changes in neuronal networks controlling movement. Quoted results are also important for clinical applications because they allow to develop new diagnostic and therapeutic techniques that can be used after nerve injury inducing motor deficits. However, till now no efficient therapy inducing satisfactory recovery was found. There is still a need to continue an advanced basic research directed to develop effective therapies. Thus the aim of this review is to compare the results of recent studies performed on various animal models in order to propose new methods for identification of mechanisms responsible for muscle deficits and propose targets for new pharmacological therapies.

Is recovery driven by central or peripheral factors? A role for the brain in recovery following intermittent-sprint exercise

PubMed Central

Minett, Geoffrey M.; Duffield, Rob

2013-01-01

Prolonged intermittent-sprint exercise (i.e., team sports) induce disturbances in skeletal muscle structure and function that are associated with reduced contractile function, a cascade of inflammatory responses, perceptual soreness, and a delayed return to optimal physical performance. In this context, recovery from exercise-induced fatigue is traditionally treated from a peripheral viewpoint, with the regeneration of muscle physiology and other peripheral factors the target of recovery strategies. The direction of this research narrative on post-exercise recovery differs to the increasing emphasis on the complex interaction between both central and peripheral factors regulating exercise intensity during exercise performance. Given the role of the central nervous system (CNS) in motor-unit recruitment during exercise, it too may have an integral role in post-exercise recovery. Indeed, this hypothesis is indirectly supported by an apparent disconnect in time-course changes in physiological and biochemical markers resultant from exercise and the ensuing recovery of exercise performance. Equally, improvements in perceptual recovery, even withstanding the physiological state of recovery, may interact with both feed-forward/feed-back mechanisms to influence subsequent efforts. Considering the research interest afforded to recovery methodologies designed to hasten the return of homeostasis within the muscle, the limited focus on contributors to post-exercise recovery from CNS origins is somewhat surprising. Based on this context, the current review aims to outline the potential contributions of the brain to performance recovery after strenuous exercise. PMID:24550837

THE REGULATION ROLE OF CAROTID BODY PERIPHERAL CHEMORECEPTORS IN PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL CONDITIONS.

PubMed

Lazovic, Biljana; Zlatkovic Svenda, Mirjana; Durmic, Tijana; Stajic, Zoran; Duric, Vesna; Zugic, Vladimir

2016-11-01

The major oxygen sensors in the human body are peripheral chemoreceptors. also known as interoreceptors- as connected with internal organs, located in the aortic arch and in the body of the common carotid artery. Chemoreceptor function under physiological conditions. Stimulation of peripheral chemoreceptors during enviromental hypoxia causes a reflex-mediated increased ventilation, followed by the increase of the muscle sympatic activity, aiming to maintain tissue oxygen homeostatis, as well as glucosae, homeostatis. Besides that, peripheral chemoreceptors interact with central chemoreceptors. responsible for carbon dioxide changes . and they are able to modulate each other. Chemoreceptor function in pathophysiological conditions. Investigations of respiratory function in many pathological processes, such as hypertension, obstructive sleep apnea, congestive heart failure and many other diseases that are presented with enhanced peripheral chemosensitivity and impaired functional sy mpatholysis ultimately determine the peripheral chemorcceptor role and significance of peripheral chemoreceptors in the process of those pathological conditions development. Considering this, the presumed influence of peripheral chemoreceptors is important in patients having the above mentioned pathology. The importance and the role of peripheral chemoreceptors in the course of the breathing control is still controversial, despite many scientific attempts to solve this problem. The main objective of this review is to give the latest data on the peripheral chemoreceptor role and to highlight the importance of peripheral chemoreceptors for maintaining of oxygen homeostasis in pateints with hypoxia caused by either physiological or pathological conditions.

Lengthening temporalis myoplasty: a surgical tool for dynamic labial commissure reanimation.

PubMed

Guerreschi, Pierre; Labbe, Daniel

2015-04-01

Lengthening temporalis myoplasty (LTM), first described by Labbé in 1997, ensures the transfers of the entire temporal muscle from the coronoid process to the upper half of the lip without interposition of aponeurotic tissue. The temporal muscle changes function because it is entirely mobilized toward another effector: the labial commissure. Thanks to brain plasticity, the muscle loses its chewing function, and after 6 months of speech rehabilitation it acquires its new smiling function. We describe technical points especially the coronoid process approaches both through an upper temporal fossa approach and a lower nasolabial fold approach. Rehabilitation starts 3 weeks after the surgery following a standardized protocol to move from a mandibular smile to a voluntary, then spontaneous, smile in three steps. The LTM is the main part of a one-stage global treatment of the paralyzed face. It constitutes a dynamic palliative treatment usually started at the sequelae stage, 18 month after the outcome of a peripheral facial paralysis. This one-stage procedure is a reproducible and relevant surgical technique in the difficult treatment of peripheral facial paralysis. It allows implementing an active muscle transfer to reanimate the labial commissure and re-create a mobile nasolabial fold. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Superficial or deep implantation of motor nerve after denervation: an experimental study--superficial or deep implantation of motor nerve.

PubMed

Askar, Ibrahím; Sabuncuoglu, Bízden Tavíl

2002-01-01

Neurorraphy, conventional nerve grafting technique, and artificial nerve conduits are not enough for repair in severe injuries of peripheral nerves, especially when there is separation of motor nerve from muscle tissue. In these nerve injuries, reinnervation is indicated for neurotization. The distal end of a peripheral nerve is divided into fascicles and implanted into the aneural zone of target muscle tissue. It is not known how deeply fascicles should be implanted into muscle tissue. A comparative study of superficial and deep implantation of separated motor nerve into muscle tissue is presented in the gastrocnemius muscle of rabbits. In this experimental study, 30 white New Zealand rabbits were used and divided into 3 groups of 10 rabbits each. In the first group (controls, group I), only surgical exposure of the gastrocnemius muscle and motor nerve (tibial nerve) was done without any injury to nerves. In the superficial implantation group (group II), tibial nerves were separated and divided into their own fascicles. These fascicles were implanted superficially into the lateral head of gastrocnemius muscle-aneural zone. In the deep implantation group (group III), the tibial nerves were separated and divided into their own fascicles. These fascicles were implanted around the center of the muscle mass, into the lateral head of the gastrocnemius muscle-aneural zone. Six months later, histopathological changes and functional recovery of the gastrocnemius muscle were investigated. Both experimental groups had less muscular weight than in the control group. It was found that functional recovery was achieved in both experimental groups, and was better in the superficial implantation group than the deep implantation group. EMG recordings revealed that polyphasic and late potentials were frequently seen in both experimental groups. Degeneration and regeneration of myofibrils were observed in both experimental groups. New motor end-plates were formed in a scattered manner in both experimental groups. However, they were more dense in the superficial implantation group than the deep implantation group. It was concluded that superficial implantation has a more powerful contractile capacity than that of deep implantation. We believe that this might arise from the high activity of glycolytic enzymes in peripheral muscle fibers of gastrocnemius muscle, decrease in insufficient intramuscular guidance apparatus, and intramuscular microneuroma formation at the insufficient neuromuscular junction since the motor nerve had less route to muscle fibers. Copyright 2002 Wiley-Liss, Inc.

Recovery from Bell Palsy after Transplantation of Peripheral Blood Mononuclear Cells and Platelet-Rich Plasma.

PubMed

Seffer, Istvan; Nemeth, Zoltan

2017-06-01

Peripheral blood mononuclear cells (PBMCs) are multipotent, and plasma contains growth factors involving tissue regeneration. We hypothesized that transplantation of PBMC-plasma will promote the recovery of paralyzed facial muscles in Bell palsy. This case report describes the effects of PBMC-plasma transplantations in a 27-year-old female patient with right side Bell palsy. On the affected side of the face, the treatment resulted in both morphological and functional recovery including voluntary facial movements. These findings suggest that PBMC-plasma has the capacity of facial muscle regeneration and provides a promising treatment strategy for patients suffering from Bell palsy or other neuromuscular disorders.

Peripheral Vascular Disease: The Beneficial Effect of Exercise in Peripheral Vascular Diseases Based on Clinical Trials.

PubMed

Elnady, Basant M; Saeed, Ayman

2017-01-01

Intermittent claudication (IC) due to peripheral artery diseases (PAD) is one of the disabling disease that can affect quality of life (QOL) and functional status of capacity. It is characterized by cramping pain which develops with exercise and eliminated by rest secondary to decrease blood flow to the muscles. The annual incidence rate is increased with age. Exercise rehabilitation has a great impact in improving the functional capacity and prevent the functional disability. The available evidences from current studies have showed that exercise therapy is considered the primary treatment in PAD, which in consequently improves the QOL. In this chapter we will illustrate the current available evidences which support exercise benefit and outcomes in PAD with IC.

Granulocyte colony-stimulating factor (G-CSF) positive effects on muscle fiber degeneration and gait recovery after nerve lesion in MDX mice

PubMed Central

Simões, Gustavo F; Benitez, Suzana U; Oliveira, Alexandre L R

2014-01-01

Background G-CSF has been shown to decrease inflammatory processes and to act positively on the process of peripheral nerve regeneration during the course of muscular dystrophy. Aims The aims of this study were to investigate the effects of treatment of G-CSF during sciatic nerve regeneration and histological analysis in the soleus muscle in MDX mice. Methods Six-week-old male MDX mice underwent left sciatic nerve crush and were G-CSF treated at 7 days prior to and 21 days after crush. Ten and twenty-one days after surgery, the mice were euthanized, and the sciatic nerves were processed for immunohistochemistry (anti-p75NTR and anti-neurofilament) and transmission electron microscopy. The soleus muscles were dissected out and processed for H&E staining and subsequent morphologic analysis. Motor function analyses were performed at 7 days prior to and 21 days after sciatic crush using the CatWalk system and the sciatic nerve index. Results Both groups treated with G-CSF showed increased p75NTR and neurofilament expression after sciatic crush. G-CSF treatment decreased the number of degenerated and regenerated muscle fibers, thereby increasing the number of normal muscle fibers. Conclusions The reduction in p75NTR and neurofilament indicates a decreased regenerative capacity in MDX mice following a lesion to a peripheral nerve. The reduction in motor function in the crushed group compared with the control groups may reflect the cycles of muscle degeneration/regeneration that occur postnatally. Thus, G-CSF treatment increases motor function in MDX mice. Nevertheless, the decrease in baseline motor function in these mice is not reversed completely by G-CSF. PMID:25328849

Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy

PubMed Central

Magown, Philippe; Shettar, Basavaraj; Zhang, Ying; Rafuse, Victor F.

2015-01-01

Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies. PMID:26460719

A peripheral governor regulates muscle contraction.

PubMed

MacIntosh, Brian R; Shahi, M Reza S

2011-02-01

Active skeletal muscles are capable of keeping the global [adenosine triphosphate (ATP)] reasonably constant during exercise, whether it is mild exercise, activating a few motor units, or all-out exercise using a substantial mass of muscle. This could only be accomplished if there were regulatory processes in place not only to replenish ATP as quickly as possible, but also to modulate the rate of ATP use when that rate threatens to exceed the rate of ATP replenishment, a situation that could lead to metabolic catastrophe. This paper proposes that there is a regulatory process or "peripheral governor" that can modulate activation of muscle to avoid metabolic catastrophe. A peripheral governor, working at the cellular level, should be able to reduce the cellular rate of ATP hydrolysis associated with muscle contraction by attenuating activation. This would necessarily cause something we call peripheral fatigue (i.e., reduced contractile response to a given stimulation). There is no doubt that peripheral fatigue occurs. It has been demonstrated in isolated muscles, in muscles in situ with no central nervous system input, and in intact human subjects performing voluntary exercise with small muscle groups or doing whole-body exercise. The regulation of muscle activation is achieved in at least 3 ways (decreasing membrane excitability, inhibiting Ca2+ release through ryanodine receptors, and decreasing the availability of Ca2+ in the sarcoplasmic reticulum), making this a highly redundant control system. The peripheral governor attenuates cellular activation to reduce the metabolic demand, thereby preserving ATP and the integrity of the cell.

Evaluation of peripheral muscle strength of patients undergoing elective cardiac surgery: a longitudinal study

PubMed Central

Santos, Kelli Maria Souza; de Cerqueira Neto, Manoel Luiz; Carvalho, Vitor Oliveira; de Santana Filho, Valter Joviniano; da Silva Junior, Walderi Monteiro; Araújo Filho, Amaro Afrânio; Cerqueira, Telma Cristina Fontes; Cacau, Lucas de Assis Pereira

2014-01-01

Introduction Peripheral muscle strength has been little explored in the literature in the context of cardiac rehabilitation. Objective To evaluate the peripheral muscle strength of patients undergoing elective cardiac surgery. Methods This was a longitudinal observational study. The peripheral muscle strength was measured using isometric dynamometry lower limb (knee extensors and flexors) at three different times: preoperatively (M1), the day of discharge (M2) and hospital discharge (M3). Participants received physiotherapy pre and postoperatively during the days of hospitalization during the morning and afternoon. Results Twenty-two patients were evaluated. The values of peripheral muscle strength of knee extensors preoperative found were about 50% lower than those predicted for the healthy population. When comparing muscle strength prior (M1), with the remaining evaluation, found himself in a fall of 29% for the movement of knee extension and 25% for knee flexion in M2 and a decrease of 10% movement for knee extension and 13% for knee flexion in M3 when comparing with M1. Conclusion The values of peripheral muscle strength prior of the study patients were lower than predicted for the healthy population of the same age. After the surgical event this reduction is even more remarkable, being reestablished until the time of discharge, to values close to baseline. PMID:25372909

Evaluation of peripheral muscle strength of patients undergoing elective cardiac surgery: a longitudinal study.

PubMed

Santos, Kelli Maria Souza; Cerqueira Neto, Manoel Luiz de; Carvalho, Vitor Oliveira; Santana Filho, Valter Joviniano de; Silva Junior, Walderi Monteiro da; Araújo Filho, Amaro Afrânio; Cerqueira, Telma Cristina Fontes; Cacau, Lucas de Assis Pereira

2014-01-01

Peripheral muscle strength has been little explored in the literature in the context of cardiac rehabilitation. To evaluate the peripheral muscle strength of patients undergoing elective cardiac surgery. This was a longitudinal observational study. The peripheral muscle strength was measured using isometric dynamometry lower limb (knee extensors and flexors) at three different times: preoperatively (M1), the day of discharge (M2) and hospital discharge (M3). Participants received physiotherapy pre and postoperatively during the days of hospitalization during the morning and afternoon. Twenty-two patients were evaluated. The values of peripheral muscle strength of knee extensors preoperative found were about 50% lower than those predicted for the healthy population. When comparing muscle strength prior (M1), with the remaining evaluation, found himself in a fall of 29% for the movement of knee extension and 25% for knee flexion in M2 and a decrease of 10% movement for knee extension and 13% for knee flexion in M3 when comparing with M1. The values of peripheral muscle strength prior of the study patients were lower than predicted for the healthy population of the same age. After the surgical event this reduction is even more remarkable, being reestablished until the time of discharge, to values close to baseline.

Peripheral magnetic stimulation to decrease spasticity in cerebral palsy.

PubMed

Flamand, Véronique H; Beaulieu, Louis-David; Nadeau, Line; Schneider, Cyril

2012-11-01

Muscle spasticity in pediatric cerebral palsy limits movement and disrupts motor performance, thus its reduction is important in rehabilitation to optimize functional motor development. Our pilot study used repetitive peripheral magnetic stimulation, because this emerging technology influences spinal and cerebral synaptic transmission, and its antispastic effects were reported in adult neurologic populations. We tested whether five sessions of tibial and common peroneal nerve stimulation exerted acute and long-term effects on spasticity of the ankle plantar flexor muscles in five spastic diparetic children (mean age, 8 years and 3 months; standard deviation, 1 year and 10 months). Muscle resistance to fast stretching was measured with a manual dynamometer as a spasticity indicator. A progressive decrease was observed for the more impaired leg, reaching significance at the third session. This sustained reduction of spasticity may reflect that the peripheral stimulation improved the controls over the spinal circuitry. It thus suggests that a massive stimulation-induced recruitment of sensory afferents may be able to influence central nervous system plasticity in pediatric cerebral palsy. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of a pulmonary rehabilitation program on physical capacity, peripheral muscle function and inflammatory markers in asthmatic children and adolescents: study protocol for a randomized controlled trial.

PubMed

Reimberg, Mariana Mazzuca; Castro, Rejane Agnelo Silva; Selman, Jessyca Pachi Rodrigues; Meneses, Aline Santos; Politti, Fabiano; Mallozi, Márcia Carvalho; Wandalsen, Gustavo Falbo; Solé, Dirceu; De Angelis, Kátia; Dal Corso, Simone; Lanza, Fernanda Cordoba

2015-08-13

Individuals with chronic lung disease are more susceptible to present reduction in exercise tolerance and muscles strength not only due to pulmonary limitations but also due systemic repercussions of the pulmonary disease. The aim of this study is to assess the physical capacity, peripheral muscle function, physical activity in daily life, and the inflammatory markers in children and adolescents with asthma after pulmonary rehabilitation program. This is a study protocol of randomized controlled trial in asthmatic patients between 6 to 18 years old. The assessments will be conducted in three different days and will be performed at the beginning and at the end of the protocol. First visit: quality of life questionnaire, asthma control questionnaire, pre- and post-bronchodilator spirometry (400 μcg salbutamol), inflammatory assessment (blood collection), and cardiopulmonary exercise test on a cycle ergometer to determine aerobic capacity. Second visit: assessment of strength and endurance of the quadriceps femoris and biceps brachii muscles with concomitant electromyography to assess peripheral muscle strength. Third visit: incremental shuttle walk test (ISWT) and accelerometer to evaluate functional capacity and physical activity in daily life during 7 days. Then, the volunteers will be randomized to receive pulmonary rehabilitation program (intervention group) or chest physiotherapy + stretching exercises (control group). Both groups will have a supervised session, twice a week, each session will have 60 minutes duration, with minimum interval of 24 hours, for a period of 8 weeks. Intervention group: aerobic training (35 minutes) intensity between 60 to 80 % of the maximum workload of cardiopulmonary exercise testing or of ISWT; strength muscle training will be applied to the quadriceps femoris, biceps brachii and deltoid muscles (intensity: 40 to 70 % of maximal repetition, 3 x 8 repetition); finally the oral high-frequency oscillation device (Flutter®) will be used for 5 minutes. The control group: oral high-frequency oscillation device (Flutter®) for 10 minutes followed by the stretching of upper and lower limbs for 40 minutes. It is expected to observe the improvement in aerobic capacity, physical activity in daily life, muscle strength and quality of life of patients in the intervention group, and reduction in inflammatory markers. NCT02383069. Data of registration: 03/03/2015.

Electrostimulation of muscles as a method for the treatment and prophylaxis of hemodynamic disturbances during prolonged hypokinesia

NASA Technical Reports Server (NTRS)

Dukhin, Y. O.; Zhukovskyy, L. Y.

1980-01-01

Hemodynamic and periopheral circulation indexes were recorded before, at the end of, and 5 days after 10 days of electrostimulation for 45 min daily, at rest and after a physical loading test. It was found that stroke and minute volume, cardiac output, and regional circulation improved and heart rate and peripheral resistance decreased. The functional state of the cardiac muscle and vascular tone are improved by electrostimulation of selected groups of skeletal muscles.

Mu-Opioid Receptors in Ganglia, But Not in Muscle, Mediate Peripheral Analgesia in Rat Muscle Pain.

PubMed

Bagues, Ana; Martín, María Isabel; Higuera-Matas, Alejandro; Esteban-Hernández, Jesús; Ambrosio, Emilio; Sánchez-Robles, Eva María

2018-04-01

Previous studies have demonstrated the participation of peripheral μ-opioid receptors (MOR) in the antinociceptive effect of systemically administered morphine and loperamide in an orofacial muscle pain model, induced by hypertonic saline, but not in a spinally innervated one, in rats. In this study, we determine whether this peripheral antinociceptive effect is due to the activation of MOR localized in the muscle, ganglia, or both. To determine the local antinociceptive effect of morphine and loperamide, 2 models of acute muscle pain (trigeminal and spinal) were used. Also, to study the MOR expression, protein quantification was performed in the trigeminal and spinal ganglia, and in the muscles. The behavioral results show that the intramuscular injection of morphine and loperamide did not exert an antinociceptive effect in either muscle (morphine: P = .63, loperamide: P = .9). On the other hand, MOR expression was found in the ganglia but not in the muscles. This expression was on average 44% higher (95% confidence interval, 33.3-53.9) in the trigeminal ganglia than in the spinal one. The peripheral antinociceptive effect of systemically administered opioids may be due to the activation of MOR in ganglia. The greater expression of MOR in trigeminal ganglia could explain the higher antinociceptive effect of opioids in orofacial muscle pain than in spinal muscle pain. Therefore, peripheral opioids could represent a promising approach for the treatment of orofacial pain.

Regenerative peripheral nerve interface viability and signal transduction with an implanted electrode.

PubMed

Kung, Theodore A; Langhals, Nicholas B; Martin, David C; Johnson, Philip J; Cederna, Paul S; Urbanchek, Melanie G

2014-06-01

The regenerative peripheral nerve interface is an internal interface for signal transduction with external electronics of prosthetic limbs; it consists of an electrode and a unit of free muscle that is neurotized by a transected residual peripheral nerve. Adding a conductive polymer coating on electrodes improves electrode conductivity. This study examines regenerative peripheral nerve interface tissue viability and signal fidelity in the presence of an implanted electrode coated or uncoated with a conductive polymer. In a rat model, the extensor digitorum longus muscle was moved as a nonvascularized free tissue transfer and neurotized by the divided peroneal nerve. Either a stainless steel pad electrode (n = 8) or a pad electrode coated with poly(3,4-ethylenedioxythiophene) conductive polymer (PEDOT) (n = 8) was implanted on the muscle transfer and secured with an encircling acellular extracellular matrix. The contralateral muscle served as the control. The free muscle transfers were successfully revascularized and over time reinnervated as evidenced by serial insertional needle electromyography. Compound muscle action potentials were successfully transduced through the regenerative peripheral nerve interface. The conductive polymer coating on the implanted electrode resulted in increased recorded signal amplitude that was observed throughout the course of the study. Histologic examination confirmed axonal sprouting, elongation, and synaptogenesis within regenerative peripheral nerve interface regardless of electrode type. The regenerative peripheral nerve interface remains viable over seven months in the presence of an implanted electrode. Electrodes with and without conductive polymer reliably transduced signals from the regenerative peripheral nerve interface. Electrodes with a conductive polymer coating resulted in recording more of the regenerative peripheral nerve interface signal.

Effects of lung ventilation–perfusion and muscle metabolism–perfusion heterogeneities on maximal O2 transport and utilization

PubMed Central

Cano, I; Roca, J; Wagner, P D

2015-01-01

Previous models of O2 transport and utilization in health considered diffusive exchange of O2 in lung and muscle, but, reasonably, neglected functional heterogeneities in these tissues. However, in disease, disregarding such heterogeneities would not be justified. Here, pulmonary ventilation–perfusion and skeletal muscle metabolism–perfusion mismatching were added to a prior model of only diffusive exchange. Previously ignored O2 exchange in non-exercising tissues was also included. We simulated maximal exercise in (a) healthy subjects at sea level and altitude, and (b) COPD patients at sea level, to assess the separate and combined effects of pulmonary and peripheral functional heterogeneities on overall muscle O2 uptake ( and on mitochondrial (). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial () at sea level by 32 mmHg, but muscle by only 122 ml min−1 (–3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced by less than 1 mmHg and by 32 ml min−1 (–2.4%). Skeletal muscle heterogeneity led to a wide range of potential among muscle regions, a range that becomes narrower as increases, and in regions with a low ratio of metabolic capacity to blood flow, can exceed that of mixed muscle venous blood. For patients with severe COPD, peak was insensitive to substantial changes in the mitochondrial characteristics for O2 consumption or the extent of muscle heterogeneity. This integrative computational model of O2 transport and utilization offers the potential for estimating profiles of both in health and in diseases such as COPD if the extent for both lung ventilation–perfusion and tissue metabolism–perfusion heterogeneity is known. PMID:25640017

[Lengthening temporalis myoplasty: Technical refinements].

PubMed

Guerreschi, P; Labbé, D

2015-10-01

First described by Labbé in 1997, the lengthening temporalis myoplasty (LTM) ensures the transfer of the entire temporal muscle from the coronoid process to the upper half of the lip without interposition of aponeurotic tissue. Thanks to brain plasticity, the temporal muscle is able to change its function because it is entirely mobilized towards another effector: the labial commissure. After 6 months of speech rehabilitation, the muscle loses its chewing function and it acquires its new smiling function. We describe as far as possible all the technical points to guide surgeons who would like to perform this powerful surgical procedure. We show the coronoid process approaches both through an upper temporal fossa approach and a lower nasolabial fold approach. Rehabilitation starts 3 weeks after the surgery following a standardized protocol to move from a mandibular smile to a voluntary smile, and then a spontaneous smile in 3 steps. The LTM is the main part of a one-stage global treatment of the paralyzed face. It constitutes a dynamic palliative treatment usually started at the sequelae stage, 18 months after the outcome of a peripheral facial paralysis. This one-stage procedure is a reproducible and relevant surgical technique in the difficult treatment of peripheral facial paralysis. An active muscle is transferred to reanimate the labial commissure and to recreate a mobile nasolabial fold. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Morphological Alterations Within the Peripheral Fixation of the Iris Dilator Muscle in Eyes With Pigmentary Glaucoma

PubMed Central

Flügel-Koch, Cassandra M.; Tektas, Ozan Y.; Kaufman, Paul L.; Paulsen, Friedrich P.; Lütjen-Drecoll, Elke

2014-01-01

Purpose. To analyze the peripheral fixation of the iris dilator muscle in normal eyes and in eyes with pigmentary glaucoma (PG). Methods. Using 63 control eyes (age 18 months–99 years), the peripheral iris dilator was investigated by light microscopy, immunohistochemistry, and electron microscopy. Development was studied using 18 differently aged fetal eyes stained immunohistochemically against α-smooth muscle (SM) actin. The peripheral iris dilator muscle in PG was analyzed using semithin and ultrathin sections of six glutaraldehyde-fixed eyes from three donors aged 38, 62, and 74 years. Results. In normal eyes, the peripheral end of the iris dilator muscle is arranged in a sphincter-like manner. Arcade-shaped tendinous connections associated with myofibroblasts (iridial strands) anchor the iris dilator within the elastic–fibromuscular ciliary meshwork that also serves as fixation area for the elastic tendons of the inner ciliary muscle portions. The iridial strands are innervated and can adapt their length during accommodation. The PG eyes show incomplete circular bundles and iridial strands that are mainly anchored to the iris stroma and the flexible uveal parts of the trabecular meshwork. Conclusions. The normal anchorage of the peripheral iris dilator and its presumably neuronally regulated length adaptation stabilize the peripheral iris during accommodation. Insufficient fixation in PG could promote posterior bowing of the iris with rubbing against the zonular fibers and pigment liberation from the iris pigmented epithelium. PMID:24938519

Effects of peripheral cooling on intention tremor in multiple sclerosis

PubMed Central

Feys, P; Helsen, W; Liu, X; Mooren, D; Albrecht, H; Nuttin, B; Ketelaer, P

2005-01-01

Objective: To investigate the effect of peripheral sustained cooling on intention tremor in patients with multiple sclerosis (MS). MS induced upper limb intention tremor affects many functional activities and is extremely difficult to treat. Materials/Methods: Deep (18°C) and moderate (25°C) cooling interventions were applied for 15 minutes to 23 and 11 tremor arms of patients with MS, respectively. Deep and moderate cooling reduced skin temperature at the elbow by 13.5°C and 7°C, respectively. Evaluations of physiological variables, the finger tapping test, and a wrist step tracking task were performed before and up to 30 minutes after cooling. Results: The heart rate and the central body temperature remained unchanged throughout. Both cooling interventions reduced overall tremor amplitude and frequency proportional to cooling intensity. Tremor reduction persisted during the 30 minute post cooling evaluation period. Nerve conduction velocity was decreased after deep cooling, but this does not fully explain the reduction in tremor amplitude or the effects of moderate cooling. Cooling did not substantially hamper voluntary movement control required for accurate performance of the step tracking task. However, changes in the mechanical properties of muscles may have contributed to the tremor amplitude reduction. Conclusions: Cooling induced tremor reduction is probably caused by a combination of decreased nerve conduction velocity, changed muscle properties, and reduced muscle spindle activity. Tremor reduction is thought to relate to decreased long loop stretch reflexes, because muscle spindle discharge is temperature dependent. These findings are clinically important because applying peripheral cooling might enable patients to perform functional activities more efficiently. PMID:15716530

The role of active muscle mass in determining the magnitude of peripheral fatigue during dynamic exercise.

PubMed

Rossman, Matthew J; Garten, Ryan S; Venturelli, Massimo; Amann, Markus; Richardson, Russell S

2014-06-15

Greater peripheral quadriceps fatigue at the voluntary termination of single-leg knee-extensor exercise (KE), compared with whole-body cycling, has been attributed to confining group III and IV skeletal muscle afferent feedback to a small muscle mass, enabling the central nervous system (CNS) to tolerate greater peripheral fatigue. However, as task specificity and vastly differing systemic challenges may have complicated this interpretation, eight males were studied during constant workload trials to exhaustion at 85% of peak workload during single-leg and double-leg KE. It was hypothesized that because of the smaller muscle mass engaged during single-leg KE, a greater magnitude of peripheral quadriceps fatigue would be present at exhaustion. Vastus lateralis integrated electromyogram (iEMG) signal relative to the first minute of exercise, preexercise to postexercise maximal voluntary contractions (MVCs) of the quadriceps, and twitch-force evoked by supramaximal magnetic femoral nerve stimulation (Qtw,pot) quantified peripheral quadriceps fatigue. Trials performed with single-leg KE (8.1 ± 1.2 min; 45 ± 4 W) resulted in significantly greater peripheral quadriceps fatigue than double-leg KE (10 ± 1.3 min; 83 ± 7 W), as documented by changes in the iEMG signal (147 ± 24 vs. 85 ± 13%), MVC (-25 ± 3 vs. -12 ± 3%), and Qtw,pot (-44 ± 6 vs. -33 ± 7%), for single-leg and double-leg KE, respectively. Therefore, avoiding concerns over task specificity and cardiorespiratory limitations, this study reveals that a reduction in muscle mass permits the development of greater peripheral muscle fatigue and supports the concept that the CNS tolerates a greater magnitude of peripheral fatigue when the source of group III/IV afferent feedback is limited to a small muscle mass.

Peripheral and Central Mechanisms of Fatigue in Inflammatory and Non-Inflammatory Rheumatic Diseases

PubMed Central

Staud, Roland

2013-01-01

Fatigue is a common symptom in a large number of medical and psychological disorders including many rheumatologic illnesses. A frequent question for health care providers is related to whether reported fatigue is “in the mind” or “in the body” i.e. central or peripheral. If fatigue occurs at rest without any exertion this suggests psychological or central origins. If patients relate their fatigue mostly to physical activities including exercise then their symptoms can be considered peripheral. However, most fatiguing syndromes seem to depend on both peripheral and central mechanisms. Sometimes muscle biopsy with histochemistry may be necessary for the appropriate tissue diagnosis whereas serological tests generally provide little reliable information about the origin of muscle fatigue. Muscle function and peripheral fatigue can be quantified by contractile force and action potential measurements whereas validated questionnaires are frequently used for assessment of mental fatigue. Fatigue is a hallmark of many rheumatologic conditions including fibromyalgia, myalgic encephalitis/chronic fatigue syndrome, rheumatoid arthritis, systemic lupus, Sjogren’s syndrome and ankylosing spondylitis. Whereas many studies have focused on disease activity as a correlate to these patients’ fatigue it has become apparent that other factors including negative affect and pain are some of the most powerful predictors for fatigue. Conversely sleep problems, including insomnia seem to be less important for fatigue. There are several effective treatment strategies available for fatigued patients with rheumatologic disorders including pharmacological and non-pharmacological therapies PMID:22802155

Neurophysiological Aspects and their relationship to clinical and functional impairment in patients with Chronic Obstructive Pulmonary Disease

PubMed Central

de Miranda Rocco, Carolina Chiusoli; Sampaio, Luciana Maria Malosá; Stirbulov, Roberto; Corrêa, João Carlos Ferrari

2011-01-01

OBJECTIVE: The purpose was to assess functional (balance L–L and A–P displacement, sit‐to‐stand test (SST) and Tinetti scale – balance and gait) and neurophysiological aspects (patellar and Achilles reflex and strength) relating these responses to the BODE Index. INTRODUCTION: The neurophysiological alterations found in patients with chronic obstructive pulmonary disease (COPD) are associated with the severity of the disease. There is also involvement of peripheral muscle which, in combination with neurophysiological impairment, may further compromise the functional activity of these patients. METHODS: A cross‐sectional study design was used. Twenty‐two patients with moderate to very severe COPD (>60 years) and 16 age‐matched healthy volunteers served as the control group (CG). The subjects performed spirometry and several measures of static and dynamic balance, monosynaptic reflexes, peripheral muscle strength, SST and the 6‐minute walk test. RESULTS: The individuals with COPD had a reduced reflex response, 36.77±3.23 (p<0.05) and 43.54±6.60 (p<0.05), achieved a lower number repetitions on the SST 19.27±3.88 (p<0.05), exhibited lesser peripheral muscle strength on the femoral quadriceps muscle, 24.98±6.88 (p<0.05) and exhibited deficits in functional balance and gait on the Tinetti scale, 26.86±1.69 (p<0.05), compared with the CG. The BODE Index demonstrated correlations with balance assessment (determined by the Tinetti scale), r = 0.59 (p<0.05) and the sit‐to‐stand test, r = 0.78 (p<0.05). CONCLUSIONS: The individuals with COPD had functional and neurophysiological alterations in comparison with the control group. The BODE Index was correlated with the Tinetti scale and the SST. Both are functional tests, easy to administer, low cost and feasible, especially the SST. These results suggest a worse prognosis; however, more studies are needed to identify the causes of these changes and the repercussions that could result in their activities of daily living. PMID:21437448

SPINAL AND PERIPHERAL DRY NEEDLING VERSUS PERIPHERAL DRY NEEDLING ALONE AMONG INDIVIDUALS WITH A HISTORY OF LATERAL ANKLE SPRAIN: A RANDOMIZED CONTROLLED TRIAL

PubMed Central

Rossi, Ainsley; Blaustein, Sara; Brown, Joshua; Dieffenderfer, Kari; Ervin, Elaine; Griffin, Steven; Frierson, Elizabeth; Geist, Kathleen

2017-01-01

Background In addition to established interventions, dry needling may reduce impairments leading to greater functional abilities for individuals following ankle sprain. Hypothesis/Purpose The purpose of this study was to compare effects of spinal and peripheral dry needling (DN) with peripheral DN alone on impairments and functional performance among individuals with a history of lateral ankle sprain. Study Design Randomized controlled trial. Methods Twenty individuals with a history of lateral ankle sprain (18 bilateral, 2 unilateral) participated in this study (4 males, 16 females; mean age 28.9 + /- 9.2 years). During the first of two sessions, participants completed the Foot and Ankle Disability Index (FADI) and the Cumberland Ankle Instability Tool (CAIT) and their strength, unilateral balance, and unilateral hop test performance was assessed. Participants were randomly assigned to a spinal and peripheral DN group (SPDN), or a peripheral only DN group (PDN). Participants in the SPDN site group received DN to bilateral L5 multifidi and fibularis longus and brevis muscles on the involved lower extremity. Participants in the PDN group received DN to the fibularis muscles alone. Participants’ strength, balance and hop test performance were reassessed immediately following the intervention, and at follow-up 6-7 days later, all outcome measures were reassessed. Three-way mixed model ANOVAs and Mann-Whitney U tests assessed between group differences for outcome variables with normal distributions and non-normal distributions, respectively. Results ANOVAs showed significant group by time interaction (p<0.05) for invertor strength, significant side by group and time by group interactions (p<0.05) for plantarflexor-evertor strength, no significant findings for dorsiflexor-invertor strength, significant side by time interaction (p<0.05) for unilateral balance, significant main effect of time (p<0.05) for triple hop for distance test, and significant main effect of side (p<0.05) for the CAIT. Mann-Whitney U tests showed no significance (p>0.05) for the side hop test or FADI. Conclusion The results suggest that DN of the multifidi in addition to fibularis muscles does not result in improvements in strength, unilateral balance or unilateral hop test performance, compared to DN the fibularis muscles alone among individuals with a history of ankle sprain. PMID:29234555

Transplantated mesenchymal stem cells derived from embryonic stem cells promote muscle regeneration and accelerate functional recovery of injured skeletal muscle.

PubMed

Ninagawa, Nana Takenaka; Isobe, Eri; Hirayama, Yuri; Murakami, Rumi; Komatsu, Kazumi; Nagai, Masataka; Kobayashi, Mami; Kawabata, Yuka; Torihashi, Shigeko

2013-08-01

We previously established that mesenchymal stem cells originating from mouse embryonic stem (ES) cells (E-MSCs) showed markedly higher potential for differentiation into skeletal muscles in vitro than common mesenchymal stem cells (MSCs). Further, the E-MSCs exhibited a low risk for teratoma formation. Here we evaluate the potential of E-MSCs for differentiation into skeletal muscles in vivo and reveal the regeneration and functional recovery of injured muscle by transplantation. E-MSCs were transplanted into the tibialis anterior (TA) muscle 24 h following direct clamping. After transplantation, the myogenic differentiation of E-MSCs, TA muscle regeneration, and re-innervation were morphologically analyzed. In addition, footprints and gaits of each leg under spontaneous walking were measured by CatWalk XT, and motor functions of injured TA muscles were precisely analyzed. Results indicate that >60% of transplanted E-MSCs differentiated into skeletal muscles. The cross-sectional area of the injured TA muscles of E-MSC-transplanted animals increased earlier than that of control animals. E-MSCs also promotes re-innervation of the peripheral nerves of injured muscles. Concerning function of the TA muscles, we reveal that transplantation of E-MSCs promotes the recovery of muscles. This is the first report to demonstrate by analysis of spontaneous walking that transplanted cells can accelerate the functional recovery of injured muscles. Taken together, the results show that E-MSCs have a high potential for differentiation into skeletal muscles in vivo as well as in vitro. The transplantation of E-MSCs facilitated the functional recovery of injured muscles. Therefore, E-MSCs are an efficient cell source in transplantation.

Transplantated Mesenchymal Stem Cells Derived from Embryonic Stem Cells Promote Muscle Regeneration and Accelerate Functional Recovery of Injured Skeletal Muscle

PubMed Central

Ninagawa, Nana Takenaka; Isobe, Eri; Hirayama, Yuri; Murakami, Rumi; Komatsu, Kazumi; Nagai, Masataka; Kobayashi, Mami; Kawabata, Yuka

2013-01-01

Abstract We previously established that mesenchymal stem cells originating from mouse embryonic stem (ES) cells (E-MSCs) showed markedly higher potential for differentiation into skeletal muscles in vitro than common mesenchymal stem cells (MSCs). Further, the E-MSCs exhibited a low risk for teratoma formation. Here we evaluate the potential of E-MSCs for differentiation into skeletal muscles in vivo and reveal the regeneration and functional recovery of injured muscle by transplantation. E-MSCs were transplanted into the tibialis anterior (TA) muscle 24 h following direct clamping. After transplantation, the myogenic differentiation of E-MSCs, TA muscle regeneration, and re-innervation were morphologically analyzed. In addition, footprints and gaits of each leg under spontaneous walking were measured by CatWalk XT, and motor functions of injured TA muscles were precisely analyzed. Results indicate that >60% of transplanted E-MSCs differentiated into skeletal muscles. The cross-sectional area of the injured TA muscles of E-MSC–transplanted animals increased earlier than that of control animals. E-MSCs also promotes re-innervation of the peripheral nerves of injured muscles. Concerning function of the TA muscles, we reveal that transplantation of E-MSCs promotes the recovery of muscles. This is the first report to demonstrate by analysis of spontaneous walking that transplanted cells can accelerate the functional recovery of injured muscles. Taken together, the results show that E-MSCs have a high potential for differentiation into skeletal muscles in vivo as well as in vitro. The transplantation of E-MSCs facilitated the functional recovery of injured muscles. Therefore, E-MSCs are an efficient cell source in transplantation. PMID:23914336

Feasibility and tolerability of whole‐body, low‐intensity vibration and its effects on muscle function and bone in patients with dystrophinopathies: a pilot study

PubMed Central

Polgreen, Lynda E.; Grames, Molly; Lowe, Dawn A.; Hodges, James S.; Karachunski, Peter

2017-01-01

ABSTRACT Introduction Dystrophinopathies are X‐linked muscle degenerative disorders that result in progressive muscle weakness complicated by bone loss. This study's goal was to evaluate feasibility and tolerability of whole‐body, low‐intensity vibration (WBLIV) and its potential effects on muscle and bone in patients with Duchenne or Becker muscular dystrophy. Methods This 12‐month pilot study included 5 patients (age 5.9–21.7 years) who used a low‐intensity Marodyne LivMD plate vibrating at 30–90 Hz for 10 min/day for the first 6 months. Timed motor function tests, myometry, and peripheral quantitative computed tomography were performed at baseline and at 6 and 12 months. Results Motor function and lower extremity muscle strength remained either unchanged or improved during the intervention phase, followed by deterioration after WBLIV discontinuation. Indices of bone density and geometry remained stable in the tibia. Conclusions WBLIV was well tolerated and appeared to have a stabilizing effect on lower extremity muscle function and bone measures. Muscle Nerve 55: 875–883, 2017 PMID:27718512

The Effect of Paired Muscle Stimulation on Preparation for Movement.

PubMed

Brownjohn, Philip W; Blakemore, Rebekah L; Fox, Jonathan A; Shemmell, Jonathan

2018-06-07

Paired muscle stimulation is used clinically to facilitate the performance of motor tasks for individuals with motor dysfunction. However, the optimal temporal relationship between stimuli for enhancing movement remains unknown. We hypothesized that synchronous, muscle stimulation would increase the extent to which stimulated muscles are concurrently prepared for movement. We validated a measure of muscle-specific changes in corticomotor excitability prior to movement. We used this measure to examine the preparation of the first dorsal interosseous (FDI), abductor digiti minimi (ADM), abductor pollicis brevis (APB) muscles prior to voluntary muscle contractions before and after paired muscle stimulation at four interstimulus intervals (0, 5, 10, and 75 ms). Paired muscle stimulation increased premovement excitability in the stimulated FDI, but not in the ADM muscle. Interstimulus interval was not a significant factor in determining efficacy of the protocol. Paired stimulation, therefore, did not result in a functional association being formed between the stimulated muscles. Somatosensory potentials evoked by the muscle stimuli were small compared to those commonly elicited by stimulation of peripheral nerves, suggesting that the lack of functional association formation between muscles may be due to the small magnitude of afferent volleys from the stimulated muscles, particularly the ADM, reaching the cortex.

Impaired quality of life in growth hormone-deficient adults is independent of the altered skeletal muscle oxidative metabolism found in conditions with peripheral fatigue.

PubMed

Sinha, Akash; Hollingsworth, Kieren G; Ball, Steve; Cheetham, Tim

2014-01-01

Growth hormone-deficient (GHD) adults often report impaired quality of life (QoL) - with fatigue, a key element. This deficit can improve following GH replacement. The basis of this response is unclear. Perturbations in skeletal muscle metabolism have been demonstrated in several conditions in which fatigue is a prominent symptom. We wished to define the role of skeletal muscle metabolism in the impaired QoL observed in patients with GHD. To compare in vivo skeletal muscle mitochondrial oxidative phosphorylation using phosphorus-31 magnetic resonance spectroscopy in matched untreated GHD adults, treated GHD adults and healthy volunteers. Twenty-two untreated GHD adults, 23 treated GHD adults and 20 healthy volunteers were recruited at a regional centre. All patients underwent assessment of muscle mitochondrial function (τ₁/₂ PCr) and proton handling using spectroscopy. Fasting biochemical analyses and anthropometric measurement were obtained. All patients completed the QoL-AGHDA and physical activity assessment (IPAQ) questionnaires. Untreated and treated GHD adults complained of significantly increased fatigue and an impaired QoL (P = 0·002) when compared to healthy controls. There was no difference in maximal mitochondrial function (P = 0·53) nor pH recovery (P = 0·38) of skeletal muscle between the three groups. Untreated GHD patients had significantly lower IGF-1 than both treated GHD and healthy volunteers (P < 0·001), but there was no association between τ₁/₂ PCr and serum IGF-1 (r = -0·13, P = 0·32). The impaired QoL seen in GHD adults is not associated with the skeletal muscle spectroscopic 'footprint' of altered mitochondrial oxidative function, anaerobic glycolysis or proton clearance that are a feature of several conditions in which fatigue is a prominent feature. These data suggest that the pathophysiology of fatigue and impaired QoL in GHD may have a significant central rather than peripheral (skeletal muscle) component. © 2013 John Wiley & Sons Ltd.

Targeted Expression of Catalase to Mitochondria Protects Against Ischemic Myopathy in High-Fat Diet–Fed Mice

PubMed Central

Ryan, Terence E.; Schmidt, Cameron A.; Green, Thomas D.; Spangenburg, Espen E.; Neufer, P. Darrell

2016-01-01

Patients with type 2 diabetes respond poorly to treatments for peripheral arterial disease (PAD) and are more likely to present with the most severe manifestation of the disease, critical limb ischemia. The underlying mechanisms linking type 2 diabetes and the severity of PAD manifestation are not well understood. We sought to test whether diet-induced mitochondrial dysfunction and oxidative stress would increase the susceptibility of the peripheral limb to hindlimb ischemia (HLI). Six weeks of high-fat diet (HFD) in C57BL/6 mice was insufficient to alter skeletal muscle mitochondrial content and respiratory function or the size of ischemic lesion after HLI, despite reducing blood flow. However, 16 weeks of HFD similarly decreased ischemic limb blood flow, but also exacerbated limb tissue necrosis, increased the myopathic lesion size, reduced muscle regeneration, attenuated muscle function, and exacerbated ischemic mitochondrial dysfunction. Mechanistically, mitochondrial-targeted overexpression of catalase prevented the HFD-induced ischemic limb necrosis, myopathy, and mitochondrial dysfunction, despite no improvement in limb blood flow. These findings demonstrate that skeletal muscle mitochondria are a critical pathological link between type 2 diabetes and PAD. Furthermore, therapeutically targeting mitochondria and oxidant burden is an effective strategy to alleviate tissue loss and ischemic myopathy during PAD. PMID:27284110

Exercise Training Reverses Extrapulmonary Impairments in Smoke-exposed Mice.

PubMed

Bowen, T Scott; Aakerøy, Lars; Eisenkolb, Sophia; Kunth, Patricia; Bakkerud, Fredrik; Wohlwend, Martin; Ormbostad, Anne Marie; Fischer, Tina; Wisloff, Ulrik; Schuler, Gerhard; Steinshamn, Sigurd; Adams, Volker; Bronstad, Eivind

2017-05-01

Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease and emphysema. However, evidence on the extrapulmonary effects of smoke exposure that precede lung impairments remains unclear at present, as are data on nonpharmacological treatments such as exercise training. Three groups of mice, including control (n = 10), smoking (n = 10), and smoking with 6 wk of high-intensity interval treadmill running (n = 11), were exposed to 20 wk of fresh air or whole-body cigarette smoke. Exercise capacity (peak oxygen uptake) and lung destruction (histology) were subsequently measured, whereas the heart, peripheral endothelium (aorta), and respiratory (diaphragm) and limb (extensor digitorum longus and soleus) skeletal muscles were assessed for in vivo and in vitro function, in situ mitochondrial respiration, and molecular alterations. Smoking reduced body weight by 26% (P < 0.05) without overt airway destruction (P > 0.05). Smoking impaired exercise capacity by 15% while inducing right ventricular dysfunction by ~20%, endothelial dysfunction by ~20%, and diaphragm muscle weakness by ~15% (all P < 0.05), but these were either attenuated or reversed by exercise training (P < 0.05). Compared with controls, smoking mice had normal limb muscle and mitochondrial function (cardiac and skeletal muscle fibers); however, diaphragm measures of oxidative stress and protein degradation were increased by 111% and 65%, respectively (P < 0.05), but these were attenuated by exercise training (P < 0.05). Prolonged cigarette smoking reduced exercise capacity concomitant with functional impairments to the heart, peripheral endothelium, and respiratory muscle that preceded the development of overt emphysema. However, high-intensity exercise training was able to reverse these smoke-induced extrapulmonary impairments.

Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function.

PubMed

McManus, Jeffrey M; Lu, Hui; Cullins, Miranda J; Chiel, Hillel J

2014-08-15

To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality. Copyright © 2014 the American Physiological Society.

Morphological alterations within the peripheral fixation of the iris dilator muscle in eyes with pigmentary glaucoma.

PubMed

Flügel-Koch, Cassandra M; Tektas, Ozan Y; Kaufman, Paul L; Paulsen, Friedrich P; Lütjen-Drecoll, Elke

2014-06-17

To analyze the peripheral fixation of the iris dilator muscle in normal eyes and in eyes with pigmentary glaucoma (PG). Using 63 control eyes (age 18 months-99 years), the peripheral iris dilator was investigated by light microscopy, immunohistochemistry, and electron microscopy. Development was studied using 18 differently aged fetal eyes stained immunohistochemically against α-smooth muscle (SM) actin. The peripheral iris dilator muscle in PG was analyzed using semithin and ultrathin sections of six glutaraldehyde-fixed eyes from three donors aged 38, 62, and 74 years. In normal eyes, the peripheral end of the iris dilator muscle is arranged in a sphincter-like manner. Arcade-shaped tendinous connections associated with myofibroblasts (iridial strands) anchor the iris dilator within the elastic-fibromuscular ciliary meshwork that also serves as fixation area for the elastic tendons of the inner ciliary muscle portions. The iridial strands are innervated and can adapt their length during accommodation. The PG eyes show incomplete circular bundles and iridial strands that are mainly anchored to the iris stroma and the flexible uveal parts of the trabecular meshwork. The normal anchorage of the peripheral iris dilator and its presumably neuronally regulated length adaptation stabilize the peripheral iris during accommodation. Insufficient fixation in PG could promote posterior bowing of the iris with rubbing against the zonular fibers and pigment liberation from the iris pigmented epithelium. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

A Bionic Neural Link for peripheral nerve repair.

PubMed

Xu, Yong Ping; Yen, Shih-Cheng; Ng, Kian Ann; Liu, Xu; Tan, Ter Chyan

2012-01-01

Peripheral nerve injuries with large gaps and long nerve regrowth paths are difficult to repair using existing surgical techniques, due to nerve degeneration and muscle atrophy. This paper proposes a Bionic Neural Link (BNL) as an alternative way for peripheral nerve repair. The concept of the BNL is described, along with the hypothetical benefits. A prototype monolithic single channel BNL has been developed, which consists of 16 neural recording channels and one stimulation channel, and is implemented in a 0.35-µm CMOS technology. The BNL has been tested in in-vivo animal experiments. Full function of the BNL chip has been demonstrated.

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery

PubMed Central

Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

2016-01-01

Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8–12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk-SCs may be a practical source for autologous stem cell therapy following severe peripheral nerve injury. PMID:27846318

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery.

PubMed

Tamaki, Tetsuro; Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

2016-01-01

Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk-SCs may be a practical source for autologous stem cell therapy following severe peripheral nerve injury.

Acquired midfoot deformity and function in individuals with diabetes and peripheral neuropathy.

PubMed

Hastings, Mary K; Mueller, Michael J; Woodburn, James; Strube, Michael J; Commean, Paul; Johnson, Jeffrey E; Cheuy, Victor; Sinacore, David R

2016-02-01

Diabetes mellitus related medial column foot deformity is a major contributor to ulceration and amputation. However, little is known about the relationship between medial column alignment and function and the integrity of the soft tissues that support and move the medial column. The purposes of this study were to determine the predictors of medial column alignment and function in people with diabetes and peripheral neuropathy. 23 participants with diabetes and neuropathy had radiographs, heel rise kinematics, magnetic resonance imaging and isokinetic muscle testing to measure: 1) medial column alignment (Meary's angle--the angle between the 1st metatarsal longitudinal axis and the talar head and neck), 2) medial column function (forefoot relative to hindfoot plantarflexion during heel rise), 3) intrinsic foot muscle and fat volume, ratio of posterior tibialis to flexor digitorum tendon volume, 4) plantar fascia function (Meary's angle change from toes flat to extended) and 5) plantarflexor peak torque. Predictors of medial column alignment and function were determined using simultaneous entry multiple regression. Posterior tibialis to flexor digitorum tendon volume ratio and intrinsic foot muscle volume were significant predictors of medial column alignment (P<.05), accounting for 44% of the variance. Intrinsic foot fat volume and plantarflexor peak torque were significant predictors of medial column function (P<.05), accounting for 37% of the variance. Deterioration of medial column supporting structures predicted alignment and function. Prospective research is required to monitor alignment, structure, and function over time to inform early intervention strategies to prevent deformity, ulceration, and amputation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Crossroads between peripheral atherosclerosis, western-type diet and skeletal muscle pathophysiology: emphasis on apolipoprotein E deficiency and peripheral arterial disease.

PubMed

Sfyri, Peggy; Matsakas, Antonios

2017-07-08

Atherosclerosis is a chronic inflammatory process that, in the presence of hyperlipidaemia, promotes the formation of atheromatous plaques in large vessels of the cardiovascular system. It also affects peripheral arteries with major implications for a number of other non-vascular tissues such as the skeletal muscle, the liver and the kidney. The aim of this review is to critically discuss and assimilate current knowledge on the impact of peripheral atherosclerosis and its implications on skeletal muscle homeostasis. Accumulating data suggests that manifestations of peripheral atherosclerosis in skeletal muscle originates in a combination of increased i)-oxidative stress, ii)-inflammation, iii)-mitochondrial deficits, iv)-altered myofibre morphology and fibrosis, v)-chronic ischemia followed by impaired oxygen supply, vi)-reduced capillary density, vii)- proteolysis and viii)-apoptosis. These structural, biochemical and pathophysiological alterations impact on skeletal muscle metabolic and physiologic homeostasis and its capacity to generate force, which further affects the individual's quality of life. Particular emphasis is given on two major areas representing basic and applied science respectively: a)-the abundant evidence from a well-recognised atherogenic model; the Apolipoprotein E deficient mouse and the role of a western-type diet and b)-on skeletal myopathy and oxidative stress-induced myofibre damage from human studies on peripheral arterial disease. A significant source of reactive oxygen species production and oxidative stress in cardiovascular disease is the family of NADPH oxidases that contribute to several pathologies. Finally, strategies targeting NADPH oxidases in skeletal muscle in an attempt to attenuate cellular oxidative stress are highlighted, providing a better understanding of the crossroads between peripheral atherosclerosis and skeletal muscle pathophysiology.

Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

NASA Astrophysics Data System (ADS)

Saloman, Jami L.

Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand gated ion channels form functional complexes in nociceptors. It is also important to further elucidate peripheral anti-nociceptive mechanisms to improve clinical utilization of currently available analgesics and uncover additional therapeutic targets. A side project examined the mechanisms underlying sex differences in the anti-hyperalgesic effects of delta opioid receptors (DORs). This study provides evidence of a sex difference in the potency at DORs that is mediated by differences in the expression of ATP-sensitive potassium channels. Collectively, understanding detailed molecular events that underlie the development of pathological pain conditions could benefit future pharmacotherapies.

Nonexpanded Adipose Stromal Vascular Fraction Local Therapy on Peripheral Nerve Regeneration Using Allografts.

PubMed

Mohammadi, Rahim; Mehrtash, Moein; Mehrtash, Moeid; Sajjadi, Seyedeh-Sepideh

2016-06-01

Adipose tissue possesses a population of multi-potent stem cells which can be differentiated to a Schwann cell phenotype and may be of benefit for treatment of peripheral nerve injuries. Effects of local therapy of nonexpanded adipose stromal vascular fraction (SVF) on peripheral nerve regeneration was studied using allografts in a rat sciatic nerve model. Thirty male white Wistar rats were divided into three experimental groups (n = 10), randomly: Sham-operated group (SHAM), allograft group (ALLO), SVF-treated group (ALLO/SVF). In SHAM group left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the ALLO group the left sciatic nerve was exposed through a gluteal muscle incision and transected proximal to the tibio-peroneal bifurcation where a 10 mm segment was excised. The same procedure was performed in the ALLO/SVF group. The harvested nerves of the rats of ALLO group were served as allograft for ALLO/SVF group and vice versa. The SHAM and ALLO groups received 100 μL phosphate buffered saline and the ALLO/SVF group received 100 μL SVF (2.25 ± 0.45 × 10(7) cells) locally where the grafting was performed. Behavioral, functional, biomechanical, and gastrocnemius muscle mass showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). Histomorphometic and immunohistochemical studies also showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). Administration of nonexpanded SVF could accelerate functional recovery after nerve allografting in sciatic nerve. It may have clinical implications for the surgical management of patients after nerve transection.

Complex impairment of IA muscle proprioceptors following traumatic or neurotoxic injury.

PubMed

Vincent, Jacob A; Nardelli, Paul; Gabriel, Hanna M; Deardorff, Adam S; Cope, Timothy C

2015-08-01

The health of primary sensory afferents supplying muscle has to be a first consideration in assessing deficits in proprioception and related motor functions. Here we discuss the role of a particular proprioceptor, the IA muscle spindle proprioceptor in causing movement disorders in response to either regeneration of a sectioned peripheral nerve or damage from neurotoxic chemotherapy. For each condition, there is a single preferred and widely repeated explanation for disability of movements associated with proprioceptive function. We present a mix of published and preliminary findings from our laboratory, largely from in vivo electrophysiological study of treated rats to demonstrate newly discovered IA afferent defects that seem likely to make important contributions to movement disorders. First, we argue that reconnection of regenerated IA afferents with inappropriate targets, although often repeated as the reason for lost stretch-reflex contraction, is not a complete explanation. We present evidence that despite successful recovery of stretch-evoked sensory signaling, peripherally regenerated IA afferents retract synapses made with motoneurons in the spinal cord. Second, we point to evidence that movement disability suffered by human subjects months after discontinuation of oxaliplatin (OX) chemotherapy for some is not accompanied by peripheral neuropathy, which is the acknowledged primary cause of disability. Our studies of OX-treated rats suggest a novel additional explanation in showing the loss of sustained repetitive firing of IA afferents during static muscle stretch. Newly extended investigation reproduces this effect in normal rats with drugs that block Na(+) channels apparently involved in encoding static IA afferent firing. Overall, these findings highlight multiplicity in IA afferent deficits that must be taken into account in understanding proprioceptive disability, and that present new avenues and possible advantages for developing effective treatment. Extending the study of IA afferent deficits yielded the additional benefit of elucidating normal processes in IA afferent mechanosensory function. © 2015 Anatomical Society.

Identification of International Classification of Functioning, Disability and Health categories for patients with peripheral arterial disease.

PubMed

Vyskocil, Erich; Gruther, Wolfgang; Steiner, Irene; Schuhfried, Othmar

2014-07-01

Disease-specific categories of the International Classification of Functioning, Disability and Health have not yet been described for patients with chronic peripheral arterial obstructive disease (PAD). The authors examined the relationship between the categories of the Brief Core Sets for ischemic heart diseases with the Peripheral Artery Questionnaire and the ankle-brachial index to determine which International Classification of Functioning, Disability and Health categories are most relevant for patients with PAD. This is a retrospective cohort study including 77 patients with verified PAD. Statistical analyses of the relationship between International Classification of Functioning, Disability and Health categories as independent variables and the endpoints Peripheral Artery Questionnaire or ankle-brachial index were carried out by simple and stepwise linear regression models adjusting for age, sex, and leg (left vs. right). The stepwise linear regression model with the ankle-brachial index as dependent variable revealed a significant effect of the variables blood vessel functions and muscle endurance functions. Calculating a stepwise linear regression model with the Peripheral Artery Questionnaire as dependent variable, a significant effect of age, emotional functions, energy and drive functions, carrying out daily routine, as well as walking could be observed. This study identifies International Classification of Functioning, Disability and Health categories in the Brief Core Sets for ischemic heart diseases that show a significant effect on the ankle-brachial index and the Peripheral Artery Questionnaire score in patients with PAD. These categories provide fundamental information on functioning of patients with PAD and patient-centered outcomes for rehabilitation interventions.

Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model.

PubMed

Isaacs, Jonathan; Feher, Joseph; Shall, Mary; Vota, Scott; Fox, Michael A; Mallu, Satya; Razavi, Ashkon; Friebe, Ilvy; Shah, Sagar; Spita, Nathalie

2013-10-01

Suboptimal recovery following repair of major peripheral nerves has been partially attributed to denervation atrophy. Administration of anabolic steroids in conjunction with neurotization may improve functional recovery of chronically denervated muscle. The purpose of this study was to evaluate the effect of the administration of nandrolone on muscle recovery following prolonged denervation in a rat model. Eight groups of female Sprague-Dawley rats (15 rats per group, 120 in all) were divided into 3- or 6-month denervated hind limb and sham surgery groups and, then, nandrolone treatment groups and sham treatment groups. Evaluation of treatment effects included nerve conduction, force of contraction, comparative morphology, histology (of muscle fibers), protein electrophoresis (for muscle fiber grouping), and immunohistochemical evaluation. Although a positive trend was noted, neither reinnervated nor normal muscle showed a statistically significant increase in peak muscle force following nandrolone treatment. Indirect measures, including muscle mass (weight and diameter), muscle cell size, muscle fiber type, and satellite cell counts, all failed to support significant anabolic effect. There does not seem to be a functional benefit from nandrolone treatment following reinnervation of either mild or moderately atrophic muscle (related to prolonged denervation) in a rodent model.

Quantification of Trapezius Muscle Innervation During Neck Dissections: Cervical Plexus Versus the Spinal Accessory Nerve.

PubMed

Svenberg Lind, Clara; Lundberg, Bertil; Hammarstedt Nordenvall, Lalle; Heiwe, Susanne; Persson, Jonas K E; Hydman, Jonas

2015-11-01

Despite increasing use of selective, nerve-sparing surgical techniques during neck dissections, the reported rate of postoperative paralysis of the trapezius muscle is still high. The aim of the study is to measure and compare motor inflow to the trapezius muscle, in order to better understand the peripheral neuroanatomy. Intraoperative nerve monitoring (electroneurography) in patients undergoing routine neck dissection (n=18). The innervation of the 3 functional parts of the trapezius muscle was mapped and quantified through compound muscle action potentials. In 18/18 (100%) of the patients, the spinal accessory nerve (SAN) innervated all parts of the trapezius muscle. In 7/18 (39%) of the patients, an active motor branch from the cervical plexus was detected, equally distributed to all functional parts of the trapezius muscle, at levels comparable to the SAN. Compared to the SAN, branches from cervical plexus provide a significant amount of neural input to all parts of the trapezius muscle. Intraoperative nerve monitoring can be used in routine neck dissections to detect these branches, which may be important following surgical injury to the SAN. © The Author(s) 2015.

The role of central and peripheral muscle fatigue in postcancer fatigue: a randomized controlled trial.

PubMed

Prinsen, Hetty; van Dijk, Johannes P; Zwarts, Machiel J; Leer, Jan Willem H; Bleijenberg, Gijs; van Laarhoven, Hanneke W M

2015-02-01

Postcancer fatigue is a frequently occurring problem, impairing quality of life. Little is known about (neuro)physiological factors determining postcancer fatigue. It may be hypothesized that postcancer fatigue is characterized by low peripheral muscle fatigue and high central muscle fatigue. The aims of this study were to examine whether central and peripheral muscle fatigue differ between fatigued and non-fatigued cancer survivors and to examine the effect of cognitive behavioral therapy (CBT) on peripheral and central muscle fatigue of fatigued cancer survivors in a randomized controlled trial. Sixteen fatigued patients in the intervention group (CBT) and eight fatigued patients in the waiting list group were successfully assessed at baseline and six months later. Baseline measurements of 20 fatigued patients were compared with 20 non-fatigued patients. A twitch interpolation technique and surface electromyography were applied, respectively, during sustained contraction of the biceps brachii muscle. Muscle fiber conduction velocity (MFCV) and central activation failure (CAF) were not significantly different between fatigued and non-fatigued patients. Change scores of MFCV and CAF were not significantly different between patients in the CBT and waiting list groups. Patients in the CBT group reported a significantly larger decrease in fatigue scores than patients in the waiting list group. Postcancer fatigue is neither characterized by abnormally high central muscle fatigue nor by low peripheral muscle fatigue. These findings suggest a difference in the underlying physiological mechanism of postcancer fatigue vs. other fatigue syndromes. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Muscle fiber types composition and type identified endplate morphology of forepaw intrinsic muscles in the rat.

PubMed

Pan, Feng; Mi, Jing-Yi; Zhang, Yan; Pan, Xiao-Yun; Rui, Yong-Jun

2016-06-01

The failure to accept reinnervation is considered to be one of the reasons for the poor motor functional recovery of intrinsic hand muscles (IHMs) after nerve injury. Rat could be a suitable model to be used in simulating motor function recovery of the IHMs after nerve injury as to the similarities in function and anatomy of the muscles between human and rat. However, few studies have reported the muscle fiber types composition and endplate morphologic characteristics of intrinsic forepaw muscles (IFMs) in the rat. In this study, the myosin heavy chain isoforms and acetylcholine receptors were stained by immunofluorescence to show the muscle fiber types composition and endplates on type-identified fibers of the lumbrical muscles (LMs), interosseus muscles (IMs), abductor digiti minimi (AM) and flexor pollicis brevis (FM) in rat forepaw. The majority of IFMs fibers were labeled positively for fast-switch fiber. However, the IMs were composed of only slow-switch fiber. With the exception of the IMs, the other IFMs had a part of hybrid fibers. Two-dimensional morphological characteristics of endplates on I and IIa muscle fiber had no significant differences among the IFMs. The LMs is the most suitable IFMs of rat to stimulate reinnervation of the IHMs after nerve injury. Gaining greater insight into the muscle fiber types composition and endplate morphology in the IFMs of rat may help understand the pathological and functional changes of IFMs in rat model stimulating reinnervation of IHMs after peripheral nerve injury.

Improvement of functional recovery of transected peripheral nerve by means of chitosan grafts filled with vitamin E, pyrroloquinoline quinone and their combination.

PubMed

Azizi, Asghar; Azizi, Saeed; Heshmatian, Behnam; Amini, Keyvan

2014-01-01

Effects of vitamin E and pyrroloquinoline quinone on peripheral nerve regeneration were studied using a rat sciatic nerve transection model. Ninety male healthy White Wistar rats were divided into three experimental groups (n = 15), randomly: Sham-operation (SHAM), transected control (TC), chitosan conduit (Chit) and three treatment groups (Vit E, PQQ and PQQ + Vit E). In SHAM group after anesthesia, left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In Chit group left sciatic nerve was exposed the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a chitosan tube. In treatment groups the tube was implanted the same way and filled with Vit E, PQQ and PQQ + Vit E. Each group was subdivided into three subgroups of six animals each and were studied 4, 8, 12 weeks after surgery. Functional and electrophysiological studies, and gastrocnemius muscle mass measurement confirmed faster and better recovery of regenerated axons in Vit E + PQQ combination compared to Vit E or PQQ solely (P < 0.05). Morphometric indices of regenerated fibers showed number and diameter of the myelinated fibers in PQQ + Vit E was significantly higher than in other treatment groups. In immunohistochemistry, location of reactions to S-100 in PQQ + Vit E was clearly more positive than in other treatment groups. Response to PQQ + Vit E treatment demonstrates that it influences and improves functional recovery of peripheral nerve regeneration. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Peripheral Airway Smooth Muscle, but Not the Trachealis, Is Hypercontractile in an Equine Model of Asthma.

PubMed

Matusovsky, Oleg S; Kachmar, Linda; Ijpma, Gijs; Bates, Genevieve; Zitouni, Nedjma; Benedetti, Andrea; Lavoie, Jean-Pierre; Lauzon, Anne-Marie

2016-05-01

Heaves is a naturally occurring equine disease that shares many similarities with human asthma, including reversible antigen-induced bronchoconstriction, airway inflammation, and remodeling. The purpose of this study was to determine whether the trachealis muscle is mechanically representative of the peripheral airway smooth muscle (ASM) in an equine model of asthma. Tracheal and peripheral ASM of heaves-affected horses under exacerbation, or under clinical remission of the disease, and control horses were dissected and freed of epithelium to measure unloaded shortening velocity (Vmax), stress (force/cross-sectional area), methacholine effective concentration at which 50% of the maximum response is obtained, and stiffness. Myofibrillar Mg(2+)-ATPase activity, actomyosin in vitro motility, and contractile protein expression were also measured. Horses with heaves had significantly greater Vmax and Mg(2+)-ATPase activity in peripheral airway but not in tracheal smooth muscle. In addition, a significant correlation was found between Vmax and the time elapsed since the end of the corticosteroid treatment for the peripheral airways in horses with heaves. Maximal stress and stiffness were greater in the peripheral airways of the horses under remission compared with controls and the horses under exacerbation, potentially due to remodeling. Actomyosin in vitro motility was not different between controls and horses with heaves. These data demonstrate that peripheral ASM is mechanically and biochemically altered in heaves, whereas the trachealis behaves as in control horses. It is therefore conceivable that the trachealis muscle may not be representative of the peripheral ASM in human asthma either, but this will require further investigation.

Assessment of peripheral skeletal muscle microperfusion in a porcine model of peripheral arterial stenosis by steady-state contrast-enhanced ultrasound and Doppler flow measurement.

PubMed

Naehle, Claas P; Steinberg, Verena A; Schild, Hans; Mommertz, Gottfried

2015-05-01

Noninvasive measurement of peripheral muscle microperfusion could potentially improve diagnosis, management, and treatment of peripheral arterial disease (PAD) and thus improve patient care. Contrast-enhanced ultrasound (CEUS) as a noninvasive diagnostic tool allows quantification of muscle perfusion. Increasing data on bolus technique CEUS reflecting microperfusion are becoming available, but only limited data on steady-state CEUS for assessment of muscle microperfusion are available. Therefore, the aim of this study was to evaluate steady-state CEUS for assessment of peripheral muscle microperfusion in a PAD animal model. In a porcine animal model, peripheral muscle microperfusion was quantified by steady-state CEUS replenishment kinetics (mean transit time [mTT] and wash-in rate [WiR]) of the biceps femoris muscle during intravenous steady-state infusion of INN-sulfur hexafluoride (SonoVue; Bracco, Geneva, Switzerland). In addition, macroperfusion was quantified at the external femoral artery with a Doppler flow probe. Peripheral muscle microperfusion and Doppler flow measurements were performed bilaterally at rest and under adenosine stress (70 μg/kg body weight) before and after unilateral creation of a moderate external iliac artery stenosis. All measurements could be performed completely in 10 pigs. Compared with baseline measurements, peripheral muscle microperfusion decreased significantly during adenosine stress (rest vs adenosine stress: mTT, 7.8 ± 3.3 vs 21.2 ± 17.8 s, P = .0006; WiR, 58.4 ± 38.1 vs 25.3 ± 15.6 arbitrary units [a.u.]/s, P < .0001; Doppler flow, 122.3 ± 31.4 vs 83.6 ± 28.1 mL/min, P = .0067) and after stenosis creation (no stenosis vs stenosis: mTT, 8.1 ± 3.1 vs 29.2 ± 18.0 s, P = .0469; WiR, 53.0 ± 22.7 vs 13.6 ± 8.4 a.u./s, P = .0156; Doppler flow, 124.2 ± 41.8 vs 65.9 ± 40.0 mL/min, P = .0313). After stenosis creation, adenosine stress led to a further significant decrease of peripheral muscle microperfusion but had no effect on macroperfusion (mTT, 29.2 ± 18.0 vs 56.3 ± 38.7 s, P = .0078; WiR, 13.6 ± 8.4 vs 6.0 ± 4.1 a.u./s, P = .0078; Doppler flow, 65.9 ± 40.0 vs 79.2 ± 29.6 mL/min, P = .8125). Receiver operating characteristic curves for the presence of inflow stenosis showed an excellent area under the curve of 0.93 for mTT at rest and 0.86 for Doppler flow. Peripheral muscle microperfusion measurement by steady-state CEUS with replenishment kinetics is feasible and allows detection of muscle microperfusion changes caused by vasodilative stress alone or in combination with a moderate inflow stenosis. Steady-state CEUS offers superior diagnostic performance compared with Doppler flow measurements. Therefore, steady-state CEUS may prove to be a useful tool in diagnosis of PAD and for evaluation of new therapies. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice.

PubMed

Yuan, Xidi; Klein, Dennis; Kerscher, Susanne; West, Brian L; Weis, Joachim; Katona, Istvan; Martini, Rudolf

2018-05-09

Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly. SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging human individuals. Both in mice and humans, these alterations were accompanied by endoneurial macrophages. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by blocking a cytokine receptor, essential for macrophage survival. The treatment strongly reduced macrophage numbers and substantially improved nerve structure and muscle strength. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may be helpful for treatment weakness and reduced mobility in the elderly. Copyright © 2018 the authors 0270-6474/18/384610-11$15.00/0.

Exercise training in older adults, what effects on muscle oxygenation? A systematic review.

PubMed

Fiogbé, Elie; de Vassimon-Barroso, Verena; de Medeiros Takahashi, Anielle Cristhine

2017-07-01

To determine the effects of different modality of exercise training programs on muscle oxygenation in older adults. Relevant articles were searched in PubMed, Web of Science, Science Direct and Scopus, using the keywords: "Aged" AND "Muscle oxygenation" AND (Exercise OR "Exercise therapy" OR "Exercise Movement Techniques" OR Hydrotherapy), without limitation concerning the publication date. To be included in the full analysis, the study had to be a randomized controlled trial in which older adults participants (mean age: 65 years at least) were submitted to an exercise-training program and muscle oxygenation assessment. The searches resulted in 1238 articles from which 7 met all the inclusion criteria. The trials involved 370 older adults (68.7±1.7years), healthy and with peripheral arterial disease. Studies included resistance and endurance exercises as well as walking sessions. Training sessions were 2-6 time per week, lasted 3-24 months and with different training intensity throughout studies. After a long-term resistance training, healthy older adults showed enhanced muscle oxygen extraction capacity, regulation of vessels and vascular endothelium function; endurance training is reported to improve microvascular blood flow and matching of oxygen delivery to oxygen utilization, muscle oxidative capacity and muscle saturation, and walking sessions results in better muscle oxygen availability and muscle oxygen extraction capacity in older adults with peripheral arterial disease. This review supports the fact that depending on the clinical status of the participants and the modality, exercise training improves different aspects of the muscle oxygenation in older adults. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional imaging of muscle oxygenation using a 200-channel cw NIRS system

NASA Astrophysics Data System (ADS)

Yamamoto, Katsuyuki; Niwayama, Masatsugu; Kohata, Daisuke; Kudo, Nobuki; Hamaoka, Takatumi; Kime, Ryotaro; Katsumura, Toshihito

2001-06-01

Functional imaging of muscle oxygenation using NIRS is a promising technique for evaluation of the heterogeneity of muscle function and diagnosis of peripheral vascular disease or muscle injury. We have developed a 200-channel imaging system that can measure the changes in oxygenation and blood volume of muscles and that covers wider area than previously reported systems. Our system consisted of 40 probes, a multiplexer for switching signals to and from the probes, and a personal computer for obtaining images. In each probe, one two-wavelength LED (770 and 830 nm) and five photodiodes were mounted on a flexible substrate. In order to eliminate the influence of a subcutaneous fat layer, a correction method, which we previously developed, was also used in imaging. Thus, quantitative changes in concentrations of oxy- and deoxy-hemoglobin were obtained. Temporal resolution was 1.5 s and spatial resolution was about 20 mm, depending on probe separations. Exercise tests (isometric contraction of 50% MVC) on the thigh with and without arterial occlusion were conducted, and changes in muscle oxygenation were imaged using the developed system. Results showed that the heterogeneity of deoxygenation and reoxygenation during exercise and recovery periods, respectively, were clearly observed. These results suggest that optical imaging of dynamic change in muscle oxygenation using NIRS would be useful not only for basic physiological studies but also for clinical applications with respect to muscle functions.

Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice.

PubMed

Jackson, Kathryn C; Wohlers, Lindsay M; Lovering, Richard M; Schuh, Rosemary A; Maher, Amy C; Bonen, Arend; Koves, Timothy R; Ilkayeva, Olga; Thomson, David M; Muoio, Deborah M; Spangenburg, Espen E

2013-02-01

Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism coupled with altered mitochondrial function may also develop. The objective of this study was to use an integrative metabolic approach to identify potential areas of dysfunction that develop in skeletal muscle from ovariectomized (OVX) female mice compared with age-matched ovary-intact adult female mice (sham). The OVX mice exhibited significant increases in body weight, visceral, and inguinal fat mass compared with sham mice. OVX mice also had significant increases in skeletal muscle intramyocellular lipids (IMCL) compared with the sham animals, which corresponded to significant increases in the protein content of the fatty acid transporters CD36/FAT and FABPpm. A targeted metabolic profiling approach identified significantly lower levels of specific acyl carnitine species and various amino acids in skeletal muscle from OVX mice compared with the sham animals, suggesting a potential dysfunction in lipid and amino acid metabolism, respectively. Basal and maximal mitochondrial oxygen consumption rates were significantly impaired in skeletal muscle fibers from OVX mice compared with sham animals. Collectively, these data indicate that loss of ovarian function results in increased IMCL storage that is coupled with alterations in mitochondrial function and changes in the skeletal muscle metabolic profile.

Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice

PubMed Central

Jackson, Kathryn C.; Wohlers, Lindsay M.; Lovering, Richard M.; Schuh, Rosemary A.; Maher, Amy C.; Bonen, Arend; Koves, Timothy R.; Ilkayeva, Olga; Thomson, David M.; Muoio, Deborah M.

2013-01-01

Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism coupled with altered mitochondrial function may also develop. The objective of this study was to use an integrative metabolic approach to identify potential areas of dysfunction that develop in skeletal muscle from ovariectomized (OVX) female mice compared with age-matched ovary-intact adult female mice (sham). The OVX mice exhibited significant increases in body weight, visceral, and inguinal fat mass compared with sham mice. OVX mice also had significant increases in skeletal muscle intramyocellular lipids (IMCL) compared with the sham animals, which corresponded to significant increases in the protein content of the fatty acid transporters CD36/FAT and FABPpm. A targeted metabolic profiling approach identified significantly lower levels of specific acyl carnitine species and various amino acids in skeletal muscle from OVX mice compared with the sham animals, suggesting a potential dysfunction in lipid and amino acid metabolism, respectively. Basal and maximal mitochondrial oxygen consumption rates were significantly impaired in skeletal muscle fibers from OVX mice compared with sham animals. Collectively, these data indicate that loss of ovarian function results in increased IMCL storage that is coupled with alterations in mitochondrial function and changes in the skeletal muscle metabolic profile. PMID:23193112

Mechanical ventilation and sepsis impair protein metabolism in the diaphragm of neonatal pigs

USDA-ARS?s Scientific Manuscript database

Mechanical ventilation (MV) impairs diaphragmatic function and diminishes the ability to wean from ventilatory support in adult humans. In normal neonatal pigs, animals that are highly anabolic, endotoxin (LPS) infusion induces sepsis, reduces peripheral skeletal muscle protein synthesis rates, but ...

Classical and adaptive control of ex vivo skeletal muscle contractions using Functional Electrical Stimulation (FES)

PubMed Central

Shoemaker, Adam; Grange, Robert W.; Abaid, Nicole; Leonessa, Alexander

2017-01-01

Functional Electrical Stimulation is a promising approach to treat patients by stimulating the peripheral nerves and their corresponding motor neurons using electrical current. This technique helps maintain muscle mass and promote blood flow in the absence of a functioning nervous system. The goal of this work is to control muscle contractions from FES via three different algorithms and assess the most appropriate controller providing effective stimulation of the muscle. An open-loop system and a closed-loop system with three types of model-free feedback controllers were assessed for tracking control of skeletal muscle contractions: a Proportional-Integral (PI) controller, a Model Reference Adaptive Control algorithm, and an Adaptive Augmented PI system. Furthermore, a mathematical model of a muscle-mass-spring system was implemented in simulation to test the open-loop case and closed-loop controllers. These simulations were carried out and then validated through experiments ex vivo. The experiments included muscle contractions following four distinct trajectories: a step, sine, ramp, and square wave. Overall, the closed-loop controllers followed the stimulation trajectories set for all the simulated and tested muscles. When comparing the experimental outcomes of each controller, we concluded that the Adaptive Augmented PI algorithm provided the best closed-loop performance for speed of convergence and disturbance rejection. PMID:28273101

Pulsed laser versus electrical energy for peripheral nerve stimulation

PubMed Central

Wells, Jonathon; Konrad, Peter; Kao, Chris; Jansen, E. Duco; Mahadevan-Jansen, Anita

2010-01-01

Transient optical neural stimulation has previously been shown to elicit highly controlled, artifact-free potentials within the nervous system in a non-contact fashion without resulting in damage to tissue. This paper presents the physiologic validity of elicited nerve and muscle potentials from pulsed laser induced stimulation of the peripheral nerve in a comparative study with the standard method of electrically evoked potentials. Herein, the fundamental physical properties underlying the two techniques are contrasted. Key laser parameters for efficient optical stimulation of the peripheral nerve are detailed. Strength response curves are shown to be linear for each stimulation modality, although fewer axons can be recruited with optically evoked potentials. Results compare the relative transient energy requirements for stimulation using each technique and demonstrate that optical methods can selectively excite functional nerve stimulation. Adjacent stimulation and recording of compound nerve potentials in their entirety from optical and electrical stimulation are presented, with optical responses shown to be free of any stimulation artifact. Thus, use of a pulsed laser exhibits some advantages when compared to standard electrical means for excitation of muscle potentials in the peripheral nerve in the research domain and possibly for clinical diagnostics in the future. PMID:17537515

Muscle anatomy and dynamic muscle function in osteogenesis imperfecta type I.

PubMed

Veilleux, Louis-Nicolas; Lemay, Martin; Pouliot-Laforte, Annie; Cheung, Moira S; Glorieux, Francis H; Rauch, Frank

2014-02-01

Results of previous studies suggested that children and adolescents with osteogenesis imperfecta (OI) type I have a muscle force deficit. However, muscle function has only been assessed by static isometric force tests and not in more natural conditions such as dynamic force and power tests. The purpose of this study was to assess lower extremity dynamic muscle function and muscle anatomy in OI type I. The study was performed in the outpatient department of a pediatric orthopedic hospital. A total of 54 individuals with OI type I (6-21 years; 20 male) and 54 age- and sex-matched controls took part in this study. Calf muscle cross-sectional area and density were measured by peripheral quantitative computed tomography. Lower extremity muscle function (peak force per body weight and peak power per body mass) was measured by jumping mechanography through 5 tests: multiple two-legged hopping, multiple one-legged hopping, single two-legged jump, chair-rise test, and heel-rise test. Compared with age- and sex-matched controls, patients with OI type I had smaller muscle size (P = .04) but normal muscle density (P = .21). They also had lower average peak force and lower specific force (peak force/muscle cross-sectional area; all P < .008). Average peak power was lower in patients with OI type I but not significantly so (all P > .054). Children and adolescents with OI type I have, on average, a significant force deficit in the lower limb as measured by dynamic force tests. Nonetheless, these data also show that OI type I is compatible with normal muscle performance in some individuals.

Is there any sense in the Palisade endings of eye muscles?

PubMed Central

Lienbacher, Karoline; Mustari, Michael; Hess, Bernhard; Büttner-Ennever, Jean; Horn, Anja K.E.

2015-01-01

Palisade endings (PEs), which are unique to the eye muscles, are associated with multiply innervated muscle fibers. They lie at the myotendinous junctions and form a cap around the muscle fiber tip. They are found in all animals investigated so far, but their function is not known. Recently, we demonstrated that cell bodies of PEs and tendon organs lie around the periphery of the oculomotor nucleus in the C- and S-groups. A morphological analysis of these peripheral neurons revealed the existence of different populations within the C-group. We propose that a small group of round or spindle-shaped cells gives rise to PEs, and another group of multipolar neurons provide the multiple motor endings. If PEs have a sensory function, then their cell body location close to motor neurons would be in an ideal location to control tension in extraocular muscles; in the case of the C-group, its proximity to the preganglionic neurons of the Edinger–Westphal nucleus would permit its participation in the near response. Despite their unusual properties, PEs may have a sensory function. PMID:21950969

Is there any sense in the Palisade endings of eye muscles?

PubMed

Lienbacher, Karoline; Mustari, Michael; Hess, Bernhard; Büttner-Ennever, Jean; Horn, Anja K E

2011-09-01

Palisade endings (PEs), which are unique to the eye muscles, are associated with multiply innervated muscle fibers. They lie at the myotendinous junctions and form a cap around the muscle fiber tip. They are found in all animals investigated so far, but their function is not known. Recently, we demonstrated that cell bodies of PEs and tendon organs lie around the periphery of the oculomotor nucleus in the C- and S-groups. A morphological analysis of these peripheral neurons revealed the existence of different populations within the C-group. We propose that a small group of round or spindle-shaped cells gives rise to PEs, and another group of multipolar neurons provide the multiple motor endings. If PEs have a sensory function, then their cell body location close to motor neurons would be in an ideal location to control tension in extraocular muscles; in the case of the C-group, its proximity to the preganglionic neurons of the Edinger-Westphal nucleus would permit its participation in the near response. Despite their unusual properties, PEs may have a sensory function. © 2011 New York Academy of Sciences.

Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys

NASA Astrophysics Data System (ADS)

Brill, N. A.; Naufel, S. N.; Polasek, K.; Ethier, C.; Cheesborough, J.; Agnew, S.; Miller, L. E.; Tyler, D. J.

2018-06-01

Objective. The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. Approach. To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. Main result. A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. Significance. FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

Functional Expression of Two Neuronal Nicotinic Acetylcholine Receptors from cDNA Clones Identifies a Gene Family

NASA Astrophysics Data System (ADS)

Boulter, Jim; Connolly, John; Deneris, Evan; Goldman, Dan; Heinemann, Steven; Patrick, Jim

1987-11-01

A family of genes coding for proteins homologous to the α subunit of the muscle nicotinic acetylcholine receptor has been identified in the rat genome. These genes are transcribed in the central and peripheral nervous systems in areas known to contain functional nicotinic receptors. In this paper, we demonstrate that three of these genes, which we call alpha3, alpha4, and beta2, encode proteins that form functional nicotinic acetylcholine receptors when expressed in Xenopus oocytes. Oocytes expressing either alpha3 or alpha4 protein in combination with the beta2 protein produced a strong response to acetylcholine. Oocytes expressing only the alpha4 protein gave a weak response to acetylcholine. These receptors are activated by acetylcholine and nicotine and are blocked by Bungarus toxin 3.1. They are not blocked by α -bungarotoxin, which blocks the muscle nicotinic acetylcholine receptor. Thus, the receptors formed by the alpha3, alpha4, and beta2 subunits are pharmacologically similar to the ganglionic-type neuronal nicotinic acetylcholine receptor. These results indicate that the alpha3, alpha4, and beta2 genes encode functional nicotinic acetylcholine receptor subunits that are expressed in the brain and peripheral nervous system.

Whole-body vibration and blood flow and muscle oxygenation: a meta-analysis.

PubMed

Games, Kenneth E; Sefton, JoEllen M; Wilson, Alan E

2015-05-01

The use and popularity of whole-body vibration (WBV) has increased in recent years, but there is a lack of consensus in the literature about the effectiveness of the treatment. To quantitatively examine the effects of WBV on muscle oxygenation and peripheral blood flow in healthy adults. We searched Web of Science and PubMed databases and reference lists from relevant articles using the key terms whole body vibration, whole-body vibration, WBV, blood flow, peripheral blood flow, oxygenation, muscle oxygenation, circulation, circulatory, near infrared spectroscopy, NIRS, and power Doppler. Key terms were searched using single word and combination searches. No date range was specified. Criteria for inclusion were (1) use of a commercially available WBV device, (2) a human research model, (3) a pre-WBV condition and at least 1 WBV experimental condition, and (4) reporting of unstandardized means and standard deviations of muscle oxygenation or peripheral blood flow. Means, standard deviations, and sample sizes were extracted from the text, tables, and figures of included studies. A total of 35 and 90 data points were extracted for the muscle-oxygenation and blood-flow meta-analyses, respectively. Data for each meta-analysis were combined and analyzed using meta-analysis software. Weighted, random-effects meta-analyses using the Hedges g metric were completed for muscle oxygenation and blood flow. We then conducted follow-up analyses using the moderator variables of vibration type, vibration time, vibration frequency, measurement location, and sample type. We found 18 potential articles. Further examination yielded 10 studies meeting the inclusion criteria. Whole-body vibration was shown to positively influence peripheral blood flow. Additionally, the moderators of vibration type and frequency altered the influence of WBV on blood flow. Overall, WBV did not alter muscle oxygenation; however, when the measurement site was considered, muscle oxygenation increased or decreased depending on the location. Acute bouts of WBV increase peripheral blood flow but do not alter skeletal muscle oxygenation. Vibration type appears to be the most important factor influencing both muscle oxygenation and peripheral blood flow.

Whole-Body Vibration and Blood Flow and Muscle Oxygenation: A Meta-Analysis

PubMed Central

Games, Kenneth E.; Sefton, JoEllen M.; Wilson, Alan E.

2015-01-01

Context: The use and popularity of whole-body vibration (WBV) has increased in recent years, but there is a lack of consensus in the literature about the effectiveness of the treatment. Objective: To quantitatively examine the effects of WBV on muscle oxygenation and peripheral blood flow in healthy adults. Data Sources: We searched Web of Science and PubMed databases and reference lists from relevant articles using the key terms whole body vibration, whole-body vibration, WBV, blood flow, peripheral blood flow, oxygenation, muscle oxygenation, circulation, circulatory, near infrared spectroscopy, NIRS, and power Doppler. Key terms were searched using single word and combination searches. No date range was specified. Study Selection: Criteria for inclusion were (1) use of a commercially available WBV device, (2) a human research model, (3) a pre-WBV condition and at least 1 WBV experimental condition, and (4) reporting of unstandardized means and standard deviations of muscle oxygenation or peripheral blood flow. Data Extraction: Means, standard deviations, and sample sizes were extracted from the text, tables, and figures of included studies. A total of 35 and 90 data points were extracted for the muscle-oxygenation and blood-flow meta-analyses, respectively. Data for each meta-analysis were combined and analyzed using meta-analysis software. Weighted, random-effects meta-analyses using the Hedges g metric were completed for muscle oxygenation and blood flow. We then conducted follow-up analyses using the moderator variables of vibration type, vibration time, vibration frequency, measurement location, and sample type. Data Synthesis: We found 18 potential articles. Further examination yielded 10 studies meeting the inclusion criteria. Whole-body vibration was shown to positively influence peripheral blood flow. Additionally, the moderators of vibration type and frequency altered the influence of WBV on blood flow. Overall, WBV did not alter muscle oxygenation; however, when the measurement site was considered, muscle oxygenation increased or decreased depending on the location. Conclusions: Acute bouts of WBV increase peripheral blood flow but do not alter skeletal muscle oxygenation. Vibration type appears to be the most important factor influencing both muscle oxygenation and peripheral blood flow. PMID:25974682

Are Females More Resistant to Extreme Neuromuscular Fatigue?

PubMed

Temesi, John; Arnal, Pierrick J; Rupp, Thomas; Féasson, Léonard; Cartier, Régine; Gergelé, Laurent; Verges, Samuel; Martin, Vincent; Millet, Guillaume Y

2015-07-01

Despite interest in the possibility of females outperforming males in ultraendurance sporting events, little is known about the sex differences in fatigue during prolonged locomotor exercise. This study investigated possible sex differences in central and peripheral fatigue in the knee extensors and plantar flexors resulting from a 110-km ultra-trail-running race. Neuromuscular function of the knee extensors and plantar flexors was evaluated via transcranial magnetic stimulation (TMS) and electrical nerve stimulation before and after an ultra-trail-running race in 20 experienced ultraendurance trail runners (10 females and 10 males matched by percent of the winning time by sex) during maximal and submaximal voluntary contractions and in relaxed muscle. Maximal voluntary knee extensor torque decreased more in males than in females (-38% vs -29%, P = 0.006) although the reduction in plantar flexor torque was similar between sexes (-26% vs -31%). Evoked mechanical plantar flexor responses decreased more in males than in females (-23% vs -8% for potentiated twitch amplitude, P = 0.010), indicating greater plantar flexor peripheral fatigue in males. Maximal voluntary activation assessed by TMS and electrical nerve stimulation decreased similarly in both sexes for both muscle groups. Indices of knee extensor peripheral fatigue and corticospinal excitability and inhibition changes were also similar for both sexes. Females exhibited less peripheral fatigue in the plantar flexors than males did after a 110-km ultra-trail-running race and males demonstrated a greater decrease in maximal force loss in the knee extensors. There were no differences in the magnitude of central fatigue for either muscle group or TMS-induced outcomes. The lower level of fatigue in the knee extensors and peripheral fatigue in the plantar flexors could partly explain the reports of better performance in females in extreme duration running races as race distance increases.

Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats.

PubMed

Higashino, Kosaku; Matsuura, Tetsuya; Suganuma, Katsuyoshi; Yukata, Kiminori; Nishisho, Toshihiko; Yasui, Natsuo

2013-05-20

Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.

Mutations in the Drosophila neuroglian cell adhesion molecule affect motor neuron pathfinding and peripheral nervous system patterning.

PubMed

Hall, S G; Bieber, A J

1997-03-01

We have identified and characterized three embryonic lethal mutations that alter or abolish expression of Drosophila Neuroglian and have used these mutations to analyze Neuroglian function during development. Neuroglian is a member of the immunoglobulin superfamily. It is expressed by a variety of cell types during embryonic development, including expression on motoneurons and the muscle cells that they innervate. Examination of the nervous systems of neuroglian mutant embryos reveals that motoneurons have altered pathfinding trajectories. Additionally, the sensory cell bodies of the peripheral nervous system display altered morphology and patterning. Using a temperature-sensitive mutation, the phenocritical period for Neuroglian function was determined to occur during late embryogenesis, an interval which coincides with the period during which neuromuscular connections and the peripheral nervous system pattern are established.

Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

PubMed Central

Sánchez, Mikel; Garate, Ane; Delgado, Diego; Padilla, Sabino

2017-01-01

Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery. PMID:28250739

Is the notion of central fatigue based on a solid foundation?

PubMed

Contessa, Paola; Puleo, Alessio; De Luca, Carlo J

2016-02-01

Exercise-induced muscle fatigue has been shown to be the consequence of peripheral factors that impair muscle fiber contractile mechanisms. Central factors arising within the central nervous system have also been hypothesized to induce muscle fatigue, but no direct empirical evidence that is causally associated to reduction of muscle force-generating capability has yet been reported. We developed a simulation model to investigate whether peripheral factors of muscle fatigue are sufficient to explain the muscle force behavior observed during empirical studies of fatiguing voluntary contractions, which is commonly attributed to central factors. Peripheral factors of muscle fatigue were included in the model as a time-dependent decrease in the amplitude of the motor unit force twitches. Our simulation study indicated that the force behavior commonly attributed to central fatigue could be explained solely by peripheral factors during simulated fatiguing submaximal voluntary contractions. It also revealed important flaws regarding the use of the interpolated twitch response from electrical stimulation of the muscle as a means for assessing central fatigue. Our analysis does not directly refute the concept of central fatigue. However, it raises important concerns about the manner in which it is measured and about the interpretation of the commonly accepted causes of central fatigue and questions the very need for the existence of central fatigue. Copyright © 2016 the American Physiological Society.

Quantification of the proportion of motor neurons recruited by transcranial electrical stimulation during intraoperative motor evoked potential monitoring.

PubMed

Tsutsui, Shunji; Yamada, Hiroshi; Hashizume, Hiroshi; Minamide, Akihito; Nakagawa, Yukihiro; Iwasaki, Hiroshi; Yoshida, Munehito

2013-12-01

Transcranial motor evoked potentials (TcMEPs) are widely used to monitor motor function during spinal surgery. However, they are much smaller and more variable in amplitude than responses evoked by maximal peripheral nerve stimulation, suggesting that a limited number of spinal motor neurons to the target muscle are excited by transcranial stimulation. The aim of this study was to quantify the proportion of motor neurons recruited during TcMEP monitoring under general anesthesia. In twenty patients who underwent thoracic and/or lumbar spinal surgery with TcMEP monitoring, the triple stimulation technique (TST) was applied to the unilateral upper arm intraoperatively. Total intravenous anesthesia was employed. Trains of four stimuli were delivered with maximal intensity and an inter-pulse interval of 1.5 ms. TST responses were recorded from the abductor digiti minimi muscle, and the negative peak amplitude and area were measured and compared between the TST test (two collisions between transcranial and proximal and distal peripheral stimulation) and control response (two collisions between two proximal and one distal peripheral stimulation). The highest degree of superimposition of the TST test and control responses was chosen from several trials per patient. The average ratios (test:control) were 17.1 % (range 1.8-38 %) for the amplitudes and 21.6 % (range 2.9-40 %) for the areas. The activity of approximately 80 % of the motor units to the target muscle cannot be detected by TcMEP monitoring. Therefore, changes in evoked potentials must be interpreted cautiously when assessing segmental motor function with TcMEP monitoring.

Motor neuron activation in peripheral nerves using infrared neural stimulation

NASA Astrophysics Data System (ADS)

Peterson, E. J.; Tyler, D. J.

2014-02-01

Objective. Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach. The rabbit sciatic nerve was stimulated extraneurally with 1875 nm wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results. 81% of nerves tested were sensitive to INS, with 1.7 ± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2-9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance. The observed selectivity of INS indicates that it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS.

Motor Neuron Activation in Peripheral Nerves Using Infrared Neural Stimulation

PubMed Central

Peterson, EJ; Tyler, DJ

2014-01-01

Objective Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach The rabbit sciatic nerve was stimulated extraneurally with 1875 nm-wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results 81% of nerves tested were sensitive to INS, with 1.7± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2–9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance The observed selectivity of INS indicates it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS. PMID:24310923

Aerobic capacity and skeletal muscle function in children with asthma.

PubMed

Villa, Fabiane; Castro, Ana Paula Beltran Moschione; Pastorino, Antonio Carlos; Santarém, José Maria; Martins, Milton Arruda; Jacob, Cristina Miuki Abe; Carvalho, Celso Ricardo

2011-06-01

Peripheral muscle strength and endurance are decreased in patients with chronic pulmonary diseases and seem to contribute to patients' exercise intolerance. However, the authors are not aware of any studies evaluating peripheral muscle function in children with asthma. It seems to be implied that children with asthma have lower aerobic fitness, but there are limited studies comparing the aerobic capacity of children with and without asthma. The present study aimed to evaluate muscle strength and endurance in children with persistent asthma and their association with aerobic capacity and inhaled corticosteroid consumption. Forty children with mild persistent asthma (MPA) or severe persistent asthma (SPA) (N=20 each) and 20 children without asthma (control group) were evaluated. Upper (pectoralis and latissimus dorsi) and lower (quadriceps) muscle strength and endurance were assessed, and cardiopulmonary exercise testing was performed. Inhaled corticosteroid consumption during the last 6 and 24 months was also quantified. Children with SPA presented a reduction in peak oxygen consumption (VO(2)) (28.2±8.1 vs 34.7±6.9 ml/kg/min; p<0.01) and quadriceps endurance (43.1±6.7 vs 80.9±11.9 repetitions; p<0.05) compared with the control group, but not the MPA group (31.5±6.1 ml/kg/min and 56.7±47.7 repetitions respectively; p>0.05). Maximal upper and lower muscle strength was preserved in children with both mild and severe asthma (p>0.05). Finally, the authors observed that lower muscle endurance weakness was not associated with reductions in either peak VO(2) (r=0.22, p>0.05) or corticosteroid consumption (r=-0.31, p>0.05) in children with asthma. The findings suggest that cardiopulmonary exercise and lower limb muscle endurance should be a priority during physical training programs for children with severe asthma.

Physiological pump loading of isolated cardiac muscle.

PubMed

Paulus, W J; Claes, V A; Brutsaert, D L

1976-05-01

Cat papillary muscles were subjected to a continuously changing load, resulting from an analysis of the left ventricle as a muscle pump system. The papillary muscle was assumed to be part of a circumferential bundle of muscle fibers of a simplified ejecting ventricle. The load included the pressure--stress relationship of this ventricle and the peripheral vascular load with its inertial, resistive and capacitive components. When this loading function was imposed on a shortening muscle through an electronic feedback circuit, the time course of force development and the velocity versus force plots closely resembled data obtained in the intact heart. Analysis of mechanical work (delta 1 X f) and power (V X f) and their respective time course permitted distinction between changes of contractile performance due to (1) positive or negative inotropic interventions, (2) altered hypothetical ventricular dimensions and changed preload, and (3) the long-term load-dependent memory of cardiac muscle.

Role of neurotrophins in the development and function of neural circuits that regulate energy homeostasis.

PubMed

Fargali, Samira; Sadahiro, Masato; Jiang, Cheng; Frick, Amy L; Indall, Tricia; Cogliani, Valeria; Welagen, Jelle; Lin, Wei-Jye; Salton, Stephen R

2012-11-01

Members of the neurotrophin family, including nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5, and other neurotrophic growth factors such as ciliary neurotrophic factor and artemin, regulate peripheral and central nervous system development and function. A subset of the neurotrophin-dependent pathways in the hypothalamus, brainstem, and spinal cord, and those that project via the sympathetic nervous system to peripheral metabolic tissues including brown and white adipose tissue, muscle and liver, regulate feeding, energy storage, and energy expenditure. We briefly review the role that neurotrophic growth factors play in energy balance, as regulators of neuronal survival and differentiation, neurogenesis, and circuit formation and function, and as inducers of critical gene products that control energy homeostasis.

Myostatin-like proteins regulate synaptic function and neuronal morphology.

PubMed

Augustin, Hrvoje; McGourty, Kieran; Steinert, Joern R; Cochemé, Helena M; Adcott, Jennifer; Cabecinha, Melissa; Vincent, Alec; Halff, Els F; Kittler, Josef T; Boucrot, Emmanuel; Partridge, Linda

2017-07-01

Growth factors of the TGFβ superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner. Both myostatin and GDF11 affected synapse formation in isolated rat cortical neuron cultures, suggesting an effect on synaptogenesis beyond neuromuscular junctions. We also show that MYO acts in vivo to inhibit synaptic transmission between neurons in the escape response neural circuit of adult flies. Thus, these anti-myogenic proteins act as important inhibitors of synapse function and neuronal growth. © 2017. Published by The Company of Biologists Ltd.

Pes cavus and hereditary neuropathies: when a relationship should be suspected.

PubMed

Piazza, S; Ricci, G; Caldarazzo Ienco, E; Carlesi, C; Volpi, L; Siciliano, G; Mancuso, M

2010-12-01

The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of diseases of the peripheral nervous system. Foot deformities, including the common pes cavus, but also hammer toes and twisting of the ankle, are frequently present in patients with hereditary peripheral neuropathy, and often represent one of the first signs of the disease. Pes cavus in hereditary peripheral neuropathies is caused by imbalance between the intrinsic muscles of the foot and the muscles of the leg. Accurate clinical evaluation in patients with pes cavus is necessary to exclude or confirm the presence of peripheral neuropathy. Hereditary peripheral neuropathies should be suspected in those cases with bilateral foot deformities, in the presence of family history for pes cavus and/or gait impairment, and in the presence of neurological symptoms or signs, such as distal muscle hypotrophy of limbs. Herein, we review the hereditary peripheral neuropathies in which pes cavus plays a key role as a "spy sign," discussing the clinical and molecular features of these disorders to highlight the importance of pes cavus as a helpful clinical sign in these rare diseases.

Neutrophilic infiltration within the airway smooth muscle in patients with COPD

PubMed Central

Baraldo, S; Turato, G; Badin, C; Bazzan, E; Beghe, B; Zuin, R; Calabrese, F; Casoni, G; Maestrelli, P; Papi, A; Fabbri, L; Saetta, M

2004-01-01

Background: COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. Methods: To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. Results: Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). Conclusions: Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation. PMID:15047950

Calf muscle density is independently associated with physical function in overweight and obese older adults.

PubMed

Scott, David; Shore-Lorenti, Catherine; McMillan, Lachlan B; Mesinovic, Jakub; Clark, Ross A; Hayes, Alan; Sanders, Kerrie M; Duque, Gustavo; Ebeling, Peter R

2018-03-01

To determine whether associations of calf muscle density with physical function are independent of other determinants of functional decline in overweight and obese older adults. This was a secondary analysis of a cross-sectional study of 85 community-dwelling overweight and obese adults (mean±SD age 62.8±7.9 years; BMI 32.3±6.1 kg/m2; 58% women). Peripheral quantitative computed tomography assessed mid-calf muscle density (66% tibial length) and dual-energy X-ray absorptiometry determined visceral fat area. Fasting glucose, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and C-reactive protein (CRP) were analysed. Physical function assessments included hand grip and knee extension strength, balance path length (computerised posturography), stair climb test, Short Physical Performance Battery (SPPB) and self-reported falls efficacy (Modified Falls Efficacy Scale; M-FES). Visceral fat area, not muscle density, was independently associated with CRP and fasting glucose (B=0.025; 95% CI 0.009-0.042 and B=0.009; 0.001-0.017, respectively). Nevertheless, higher muscle density was independently associated with lower path length and stair climb time, and higher SPPB and M-FES scores (all P⟨0.05). Visceral fat area, fasting glucose and CRP did not mediate these associations. Higher calf muscle density predicts better physical function in overweight and obese older adults independent of insulin resistance, visceral adiposity or inflammation.

Mechanical ventilation alone, and in the presence of sepsis, impair protein metabolism in the diaphragm of neonatal pigs

USDA-ARS?s Scientific Manuscript database

Mechanical ventilation (MV) impairs diaphragmatic function and diminishes the ability to wean from ventilatory support in adult humans. In normal neonatal pigs, animals that are highly anabolic, endotoxin (LPS) infusion induces sepsis, reduces peripheral skeletal muscle protein synthesis rates, but ...

Severe hypoxia affects exercise performance independently of afferent feedback and peripheral fatigue.

PubMed

Millet, Guillaume Y; Muthalib, Makii; Jubeau, Marc; Laursen, Paul B; Nosaka, Kazunori

2012-04-01

To test the hypothesis that hypoxia centrally affects performance independently of afferent feedback and peripheral fatigue, we conducted two experiments under complete vascular occlusion of the exercising muscle under different systemic O(2) environmental conditions. In experiment 1, 12 subjects performed repeated submaximal isometric contractions of the elbow flexor to exhaustion (RCTE) with inspired O(2) fraction fixed at 9% (severe hypoxia, SevHyp), 14% (moderate hypoxia, ModHyp), 21% (normoxia, Norm), or 30% (hyperoxia, Hyper). The number of contractions (performance), muscle (biceps brachii), and prefrontal near-infrared spectroscopy (NIRS) parameters and high-frequency paired-pulse (PS100) evoked responses to electrical muscle stimulation were monitored. In experiment 2, 10 subjects performed another RCTE in SevHyp and Norm conditions in which the number of contractions, biceps brachii electromyography responses to electrical nerve stimulation (M wave), and transcranial magnetic stimulation responses (motor-evoked potentials, MEP, and cortical silent period, CSP) were recorded. Performance during RCTE was significantly reduced by 10-15% in SevHyp (arterial O(2) saturation, SpO(2) = ∼75%) compared with ModHyp (SpO(2) = ∼90%) or Norm/Hyper (SpO(2) > 97%). Performance reduction in SevHyp occurred despite similar 1) metabolic (muscle NIRS parameters) and functional (changes in PS100 and M wave) muscle states and 2) MEP and CSP responses, suggesting comparable corticospinal excitability and spinal and cortical inhibition between SevHyp and Norm. It is concluded that, in SevHyp, performance and central drive can be altered independently of afferent feedback and peripheral fatigue. It is concluded that submaximal performance in SevHyp is partly reduced by a mechanism related directly to brain oxygenation.

Peripheral arterial disease decreases muscle torque and functional walking capacity in elderly.

PubMed

Dziubek, Wioletta; Bulińska, Katarzyna; Stefańska, Małgorzata; Woźniewski, Marek; Kropielnicka, Katarzyna; Jasiński, Tomasz; Jasiński, Ryszard; Pilch, Urszula; Dąbrowska, Grażyna; Skórkowska-Telichowska, Katarzyna; Wojcieszczyk-Latos, Joanna; Kałka, Dariusz; Janus, Agnieszka; Zywar, Katarzyna; Paszkowski, Rafał; Szuba, Andrzej

2015-08-01

The aim of this study is to compare values of force-velocity and functional walking capacity in elderly patients with intermittent claudication with respect to the control group. The study involved 135 individuals: 85-peripheral arterial disease (PAD) group diagnosed with stage II chronic lower limb ischemia, according to Fontaine's classification, and 50-control group. The studies included an assessment of walking capacity using a six-minute walk test (6MWT) and measurement of force-velocity parameters (peak torque-PTQ, total work-TW, average power-AVGP) of the lower limbs obtained by means of a functional dynamometry under isokinetic conditions. The peripheral arterial disease group is characterized by significantly lower values of force-velocity parameters compared to the control group (p<0.005). Walking capacity in this group is significantly reduced due to significant differences in the distance covered (p<0.0001), walking speed (p<0.01), and its intensity (p<0.01). Further, a positive correlation was found between the maximum distance specified in the six-minute walk test and lower limb muscle strength in the isokinetic test. Mean values of all force-velocity parameters and walk distance were significantly higher in the control group than in the peripheral arterial disease group. In the PAD group, in both men and women, the value of the agonist/antagonist ratio of both lower limbs are lower in men and women comparing to the control group. A rehabilitation program for patients with intermittent claudication must consider exercises improving strength, exercise capacity, and endurance in patients with PAD. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Metabolic inflexibility in skeletal muscle: a prelude to the cardiometabolic syndrome?

PubMed

Thyfault, John P; Rector, R Scott; Noland, Robert C

2006-01-01

Peripheral insulin resistance, which is largely dependent on skeletal muscle, is closely linked to the development of the cardiometabolic syndrome. Metabolic flexibility is the capacity for skeletal muscle to acutely shift its reliance between lipids or glucose during fasting or postprandial conditions. Obese and insulin-resistant individuals display elevated intramuscular lipids, impaired vasculature function, decreased fatty add oxidation during fasting, and reduced postprandial glucose metabolism. Impairments in metabolic flexibility are linked to physical inactivity, excess energy intake and obesity, and genetic predisposition. Each of these factors precludes the development of insulin resistance and the cardiometabolic syndrome by mechanistic links that are not fully understood.

Peripheral metabolic actions of leptin.

PubMed

Muoio, Deborah M; Lynis Dohm, G

2002-12-01

The adipocyte-derived hormone, leptin, regulates food intake and systemic fuel metabolism; ob /ob mice, which lack functional leptin, exhibit an obesity syndrome that is similar to morbid obesity in humans. Leptin receptors are expressed most abundantly in the brain but are also present in several peripheral tissues. The role of leptin in controlling energy homeostasis has thus far focused on brain receptors and neuroendocrine pathways that regulate feeding behaviour and sympathetic nervous system activity. This chapter focuses on mounting evidence that leptin's effects on energy balance are also mediated by direct peripheral actions on key metabolic organs such as skeletal muscle, liver, pancreas and adipose tissue. Strong evidence indicates that peripheral leptin receptors regulate cellular lipid balance, favouring beta-oxidation over triacylglycerol storage. There are data to indicate that peripheral leptin also modulates glucose metabolism and insulin action; however, its precise role in controlling gluco-regulatory pathways remains uncertain and requires further investigation.

Myoneural necrosis following high-frequency electrical stimulation of the cast-immobilized rabbit hindlimb

NASA Technical Reports Server (NTRS)

Friden, J.; Lieber, R. L.; Myers, R. R.; Powell, H. C.; Hargens, A. R.

1989-01-01

The morphological and physiological effects of 4 weeks of high-frequency electrical stimulation (1 h/day, 5 days/week) on cast-immobilized rabbit hindlimbs were investigated in the tibialis anterior muscle and peroneal nerve. In 2 out of 6 animals, high-frequency stimulation with immobilization caused muscle fiber death, internalization of muscle fiber nuclei, connective tissue proliferation, inflammatory response, altered fiber size distribution and variable staining intensities. The fast-twitch fibers were predominantly affected. Two of six peripheral nerves subjected to immobilization and stimulation showed severe damage. Tetanic forces were significantly reduced in the affected muscles. Therefore, the immobilization and high-frequency stimulation may be detrimental to myoneural structure and function and, thus, this combination of therapies should be applied conservatively.

Time course of functional recovery during the first 3 mo after surgical transection and repair of nerves to the feline soleus and lateral gastrocnemius muscles.

PubMed

Gregor, Robert J; Maas, Huub; Bulgakova, Margarita A; Oliver, Alanna; English, Arthur W; Prilutsky, Boris I

2018-03-01

Locomotion outcomes after peripheral nerve injury and repair in cats have been described in the literature for the period immediately following the injury (muscle denervation period) and then again for an ensuing period of long-term recovery (at 3 mo and longer) resulting in muscle self-reinnervation. Little is known about the changes in muscle activity and walking mechanics during midrecovery, i.e., the early reinnervation period that takes place between 5 and 10 wk of recovery. Here, we investigated hindlimb mechanics and electromyogram (EMG) activity of ankle extensors in six cats during level and slope walking before and every 2 wk thereafter in a 14-wk period of recovery after the soleus (SO) and lateral gastrocnemius (LG) muscle nerves in one hindlimb were surgically transected and repaired. We found that the continued increase in SO and LG EMG magnitudes and corresponding changes in hindlimb mechanics coincided with the formation of neuromuscular synapses revealed in muscle biopsies. Throughout the recovery period, EMG magnitude of SO and LG during the stance phase and the duration of the stance-related activity were load dependent, similar to those in the intact synergistic medial gastrocnemius and plantaris. These results and the fact that EMG activity of ankle extensors and locomotor mechanics during level and upslope walking recovered 14 wk after nerve transection and repair suggest that loss of the stretch reflex in self-reinnervated muscles may be compensated by the recovered force-dependent feedback in self-reinnervated muscles, by increased central drive, and by increased gain in intermuscular motion-dependent pathways from intact ankle extensors. NEW & NOTEWORTHY This study provides new evidence that the timeline for functional recovery of gait after peripheral nerve injury and repair is consistent with the time required for neuromuscular junctions to form and muscles to reach preoperative tensions. Our findings suggest that a permanent loss of autogenic stretch reflex in self-reinnervated muscles may be compensated by recovered intermuscular force-dependent and oligosynaptic length-dependent feedback and central drive to regain adequate locomotor output capabilities during level and upslope walking.

Use of paper for treatment of a peripheral nerve trauma in the rat.

PubMed

Kauppila, T; Jyväsjärvi, E; Murtomäki, S; Mansikka, H; Pertovaara, A; Virtanen, I; Liesi, P

1997-09-29

Reinnervation of the muscles and skin in the rat hindpaw was studied after transection and attempted repair of the sciatic nerve. Reconnecting the transected nerve with lens cleaning paper was at least as effective in rejoining the transected nerves as traditional microsurgical neurorraphy. Paper induced a slightly bigger fibrous scar around the site of transection than neurorraphy, but this scar did not cause impairment of functional recovery or excessive signs of neuropathic pain. We conclude that a paper graft can be used in restorative surgery of severed peripheral nerves.

Self-reinnervated muscles lose autogenic length feedback, but intermuscular feedback can recover functional connectivity

PubMed Central

Prilutsky, Boris I.; Gregor, Robert J.; Abelew, Thomas A.; Nichols, T. Richard

2016-01-01

In this study, we sought to identify sensory circuitry responsible for motor deficits or compensatory adaptations after peripheral nerve cut and repair. Self-reinnervation of the ankle extensor muscles abolishes the stretch reflex and increases ankle yielding during downslope walking, but it remains unknown whether this finding generalizes to other muscle groups and whether muscles become completely deafferented. In decerebrate cats at least 19 wk after nerve cut and repair, we examined the influence of quadriceps (Q) muscles' self-reinnervation on autogenic length feedback, as well as intermuscular length and force feedback, among the primary extensor muscles in the cat hindlimb. Effects of gastrocnemius and soleus self-reinnervation on intermuscular circuitry were also evaluated. We found that autogenic length feedback was lost after Q self-reinnervation, indicating that loss of the stretch reflex appears to be a generalizable consequence of muscle self-reinnervation. However, intermuscular force and length feedback, evoked from self-reinnervated muscles, was preserved in most of the interactions evaluated with similar relative inhibitory or excitatory magnitudes. These data indicate that intermuscular spinal reflex circuitry has the ability to regain functional connectivity, but the restoration is not absolute. Explanations for the recovery of intermuscular feedback are discussed, based on identified mechanisms responsible for lost autogenic length feedback. Functional implications, due to permanent loss of autogenic length feedback and potential for compensatory adaptations from preserved intermuscular feedback, are discussed. PMID:27306676

Misdirection of Regenerating Axons and Functional Recovery Following Sciatic Nerve Injury in Rats

PubMed Central

Hamilton, Shirley K.; Hinkle, Marcus L.; Nicolini, Jennifer; Rambo, Lindsay N.; Rexwinkle, April M.; Rose, Sam J.; Sabatier, Manning J.; Backus, Deborah; English, Arthur W.

2013-01-01

Poor functional recovery found after peripheral nerve injury has been attributed to the misdirection of regenerating axons to reinnervate functionally inappropriate muscles. We applied brief electrical stimulation (ES) to the common fibular (CF) but not the tibial (Tib) nerve just prior to transection and repair of the entire rat sciatic nerve, to attempt to influence the misdirection of its regenerating axons. The specificity with which regenerating axons reinnervated appropriate targets was evaluated physiologically using compound muscle action potentials (M responses) evoked from stimulation of the two nerve branches above the injury site. Functional recovery was assayed using the timing of electromyography (EMG) activity recorded from the tibialis anterior (TA) and soleus (Sol) muscles during treadmill locomotion and kinematic analysis of hindlimb locomotor movements. Selective ES of the CF nerve resulted in restored M-responses at earlier times than in unstimulated controls in both TA and Sol muscles. Stimulated CF axons reinnervated inappropriate targets to a greater extent than unstimulated Tib axons. During locomotion, functional antagonist muscles, TA and Sol, were coactivated both in stimulated rats and in unstimulated but injured rats. Hindlimb kinematics in stimulated rats were comparable to untreated rats, but significantly different from intact controls. Selective ES promotes enhanced axon regeneration but does so with decreased fidelity of muscle reinnervation. Functional recovery is neither improved nor degraded, suggesting that compensatory changes in the outputs of the spinal circuits driving locomotion may occur irrespective of the extent of misdirection of regenerating axons in the periphery. PMID:21120925

Roles of neural stem cells in the repair of peripheral nerve injury.

PubMed

Wang, Chong; Lu, Chang-Feng; Peng, Jiang; Hu, Cheng-Dong; Wang, Yu

2017-12-01

Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

Relation between systemic inflammatory markers, peripheral muscle mass, and strength in limb muscles in stable COPD patients.

PubMed

Ferrari, Renata; Caram, Laura M O; Faganello, Marcia M; Sanchez, Fernanda F; Tanni, Suzana E; Godoy, Irma

2015-01-01

The aim of this study was to investigate the association between systemic inflammatory mediators and peripheral muscle mass and strength in COPD patients. Fifty-five patients (69% male; age: 64±9 years) with mild/very severe COPD (defined as forced expiratory volume in the first second [FEV1] =54%±23%) were evaluated. We evaluated serum concentrations of IL-8, CRP, and TNF-α. Peripheral muscle mass was evaluated by computerized tomography (CT); midthigh cross-sectional muscle area (MTCSA) and midarm cross-sectional muscle area (MACSA) were obtained. Quadriceps, triceps, and biceps strength were assessed through the determination of the one-repetition maximum. The multiple regression results, adjusted for age, sex, and FEV1%, showed positive significant association between MTCSA and leg extension (0.35 [0.16, 0.55]; P=0.001), between MACSA and triceps pulley (0.45 [0.31, 0.58]; P=0.001), and between MACSA and biceps curl (0.34 [0.22, 0.47]; P=0.001). Plasma TNF-α was negatively associated with leg extension (-3.09 [-5.99, -0.18]; P=0.04) and triceps pulley (-1.31 [-2.35, -0.28]; P=0.01), while plasma CRP presented negative association with biceps curl (-0.06 [-0.11, -0.01]; P=0.02). Our results showed negative association between peripheral muscle mass (evaluated by CT) and muscle strength and that systemic inflammation has a negative influence in the strength of specific groups of muscles in individuals with stable COPD. This is the first study showing association between systemic inflammatory markers and strength in upper limb muscles.

Declining Skeletal Muscle Function in Diabetic Peripheral Neuropathy.

PubMed

Parasoglou, Prodromos; Rao, Smita; Slade, Jill M

2017-06-01

The present review highlights current concepts regarding the effects of diabetic peripheral neuropathy (DPN) in skeletal muscle. It discusses the lack of effective pharmacologic treatments and the role of physical exercise intervention in limb protection and symptom reversal. It also highlights the importance of magnetic resonance imaging (MRI) techniques in providing a mechanistic understanding of the disease and helping develop targeted treatments. This review provides a comprehensive reporting on the effects of DPN in the skeletal muscle of patients with diabetes. It also provides an update on the most recent trials of exercise intervention targeting DPN pathology. Lastly, we report on emerging MRI techniques that have shown promise in providing a mechanistic understanding of DPN and can help improve the design and implementation of clinical trials in the future. Impairments in lower limb muscles reduce functional capacity and contribute to altered gait, increased fall risk, and impaired balance in patients with DPN. This finding is an important concern for patients with DPN because their falls are likely to be injurious and lead to bone fractures, poorly healing wounds, and chronic infections that may require amputation. Preliminary studies have shown that moderate-intensity exercise programs are well tolerated by patients with DPN. They can improve their cardiorespiratory function and partially reverse some of the symptoms of DPN. MRI has the potential to bring new mechanistic insights into the effects of DPN as well as to objectively measure small changes in DPN pathology as a result of intervention. Noninvasive exercise intervention is particularly valuable in DPN because of its safety, low cost, and potential to augment pharmacologic interventions. As we gain a better mechanistic understanding of the disease, more targeted and effective interventions can be designed. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Poly-3-hydroxybutyrate strips seeded with regenerative cells are effective promoters of peripheral nerve repair.

PubMed

Schaakxs, Dominique; Kalbermatten, Daniel F; Pralong, Etienne; Raffoul, Wassim; Wiberg, Mikael; Kingham, Paul J

2017-03-01

Peripheral nerve injuries are often associated with loss of nerve tissue and require a graft to bridge the gap. Autologous nerve grafts are still the 'gold standard' in reconstructive surgery but have several disadvantages, such as sacrifice of a functional nerve, neuroma formation and loss of sensation at the donor site. Bioengineered grafts represent a promising approach to address this problem. In this study, poly-3-hydroxybutyrate (PHB) strips were used to bridge a 10 mm rat sciatic nerve gap and their effects on long-term (12 weeks) nerve regeneration were compared. PHB strips were seeded with different cell types, either primary Schwann cells (SCs) or SC-like differentiated adipose-derived stem cells (dASCs) suspended in a fibrin glue matrix. The control group was PHB and fibrin matrix without cells. Functional and morphological properties of the regenerated nerve were assessed using walking track analysis, EMGs, muscle weight ratios and muscle and nerve histology. The animals treated with PHB strips seeded with SCs or dASCs showed significantly better functional ability than the control group. This correlated with less muscle atrophy and greater axon myelination in the cell groups. These findings suggest that the PHB strip seeded with cells provides a beneficial environment for nerve regeneration. Furthermore, dASCs, which are abundant and easily accessible, constitute an attractive cell source for future applications of cell therapy for the clinical repair of traumatic nerve injuries. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Complete adult neurogenesis within a Wallerian degenerating nerve expressed as an ectopic ganglion.

PubMed

Nakano, Tomonori; Kurimoto, Shigeru; Kato, Shuichi; Asano, Kenichi; Hirata, Takuma; Kiyama, Hiroshi; Hirata, Hitoshi

2018-06-01

Neurogenesis in the adult peripheral nervous system remains to be demonstrated. We transplanted embryonic neural stem cells into a Wallerian degenerating nerve graft and observed development of a nodular structure consisting of neurons, glia, and Schwann cells. Histological analysis revealed a structure loosely resembling the spinal cord, including a synaptic network that formed along the neuron. Furthermore, the new axons reinnervated the paralysed muscle, forming both de novo and revived neuromuscular junctions. Reinnervation of the paralysed muscle resulted in significantly greater mean wet muscle weight and muscle fibre cross-sectional area on the cell transplantation side than on the surgical control side (body weight 0.071 ± 0.011% vs. 0.051 ± 0.007%, p = .006; area 355.6 ± 345.2 vs. 114.0 ± 132.0 μm 2 , p < .001). Electrophysiological experiments demonstrated a functional connection between the neurons and muscle; hence, we identified this nodule as an ectopic ganglion. Surprisingly, in green rat experiments, most of these glial cells, but none of the neurons, expressed enhanced green fluorescent protein, suggesting that the cells constituting the ectopic ganglion were derived from both transplanted stem cells and endogenous stem cells. Such adult neurogenesis in a peripheral nerve related to neural stem cell transplantation has not been reported previously, and these results form the basis for a novel regenerative medicine approach in paralysed muscle. Copyright © 2018 John Wiley & Sons, Ltd.

The physiological basis of rehabilitation in chronic heart and lung disease.

PubMed

Vogiatzis, Ioannis; Zakynthinos, Spyros

2013-07-01

Cardiopulmonary rehabilitation is recognized as a core component of management of individuals with congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) that is designed to improve their physical and psychosocial condition without impacting on the primary organ impairment. This has lead the scientific community increasingly to believe that the main effects of cardiopulmonary rehabilitative exercise training are focused on skeletal muscles that are regarded as dysfunctional in both CHF and COPD. Accordingly, following completion of a cardiopulmonary rehabilitative exercise training program there are important peripheral muscular adaptations in both disease entities, namely increased capillary density, blood flow, mitochondrial volume density, fiber size, distribution of slow twitch fibers, and decreased lactic acidosis and vascular resistance. Decreased lactic acidosis at a given level of submaximal exercise not only offsets the occurrence of peripheral muscle fatigue, leading to muscle task failure and muscle discomfort, but also concurrently mitigates the additional burden on the respiratory muscles caused by the increased respiratory drive, thereby reducing dyspnea sensations. Furthermore in patients with COPD, exercise training reduces the degree of dynamic lung hyperinflation leading to improved arterial oxygen content and central hemodynamic responses, thus increasing systemic muscle oxygen availability. In patients with CHF, exercise training has beneficial direct and reflex sympathoinhibitory effects and favorable effects on normalization of neurohumoral excitation. These physiological benefits apply to all COPD and CHF patients independently of the degree of disease severity and are associated with improved exercise tolerance, functional capacity, and quality of life.

The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells.

PubMed

Dressel, Uwe; Allen, Tamara L; Pippal, Jyotsna B; Rohde, Paul R; Lau, Patrick; Muscat, George E O

2003-12-01

Lipid homeostasis is controlled by the peroxisome proliferator-activated receptors (PPARalpha, -beta/delta, and -gamma) that function as fatty acid-dependent DNA-binding proteins that regulate lipid metabolism. In vitro and in vivo genetic and pharmacological studies have demonstrated PPARalpha regulates lipid catabolism. In contrast, PPARgamma regulates the conflicting process of lipid storage. However, relatively little is known about PPARbeta/delta in the context of target tissues, target genes, lipid homeostasis, and functional overlap with PPARalpha and -gamma. PPARbeta/delta, a very low-density lipoprotein sensor, is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for approximately 40% of total body weight. Skeletal muscle is a metabolically active tissue, and a primary site of glucose metabolism, fatty acid oxidation, and cholesterol efflux. Consequently, it has a significant role in insulin sensitivity, the blood-lipid profile, and lipid homeostasis. Surprisingly, the role of PPARbeta/delta in skeletal muscle has not been investigated. We utilize selective PPARalpha, -beta/delta, -gamma, and liver X receptor agonists in skeletal muscle cells to understand the functional role of PPARbeta/delta, and the complementary and/or contrasting roles of PPARs in this major mass peripheral tissue. Activation of PPARbeta/delta by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, beta-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARbeta/delta agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPARgamma induces gene expression associated with glucose uptake, fatty acid synthesis, and lipid storage. Furthermore, we show that the PPAR-dependent reporter in the muscle carnitine palmitoyl-transferase-1 promoter is directly regulated by PPARbeta/delta, and not PPARalpha in skeletal muscle cells in a PPARgamma coactivator-1-dependent manner. This study demonstrates that PPARs have distinct roles in skeletal muscle cells with respect to the regulation of lipid, carbohydrate, and energy homeostasis. Moreover, we surmise that PPARbeta/delta agonists would increase fatty acid catabolism, cholesterol efflux, and energy expenditure in muscle, and speculate selective activators of PPARbeta/delta may have therapeutic utility in the treatment of hyperlipidemia, atherosclerosis, and obesity.

Comparative Evaluation of Chitosan Nerve Guides with Regular or Increased Bendability for Acute and Delayed Peripheral Nerve Repair: A Comprehensive Comparison with Autologous Nerve Grafts and Muscle-in-Vein Grafts.

PubMed

Stößel, Maria; Wildhagen, Vivien M; Helmecke, Olaf; Metzen, Jennifer; Pfund, Charlotte B; Freier, Thomas; Haastert-Talini, Kirsten

2018-05-08

Reconstruction of joint-crossing digital nerves requires the application of nerve guides with a much higher flexibility than used for peripheral nerve repair along larger bones. Nevertheless, collapse-resistance should be preserved to avoid secondary damage to the regrowing nerve tissue. In recent years, we presented chitosan nerve guides (CNGs) to be highly supportive for the regeneration of critical gap length peripheral nerve defects in the rat. Now, we evidently increased the bendability of regular CNGs (regCNGs) by developing a wavy wall structure, that is, corrugated CNGs (corrCNGs). In a comprehensive in vivo study, we compared both types of CNGs with clinical gold standard autologous nerve grafts (ANGs) and muscle-in-vein grafts (MVGs) that have recently been highlighted in the literature as a suitable alternative to ANGs. We reconstructed rat sciatic nerves over a critical gap length of 15 mm either immediately upon transection or after a delay period of 45 days. Electrodiagnostic measurements were applied to monitor functional motor recovery at 60, 90, 120, and 150 (only delayed repair) days postreconstruction. Upon explanation, tube properties were analyzed. Furthermore, distal nerve ends were evaluated using histomorphometry, while connective tissue specimens were subjected to immunohistological stainings. After 120 days (acute repair) or 150 days (delayed repair), respectively, compression-stability of regCNGs was slightly increased while it remained stable in corrCNGs. In both substudies, regCNGs and corrCNGs supported functional recovery of distal plantar muscles in a similar way and to a greater extent when compared with MVGs, while ANGs demonstrated the best support of regeneration. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

The Effect of Electrical Stimulation in Improving Muscle Tone (Clinical)

NASA Astrophysics Data System (ADS)

Azman, M. F.; Azman, A. W.

2017-11-01

Electrical stimulation (ES) and also known as neuromuscular electrical stimulation (NMES) and transcutaneous electrical stimulation (TES) involves the use of electrical current to stimulate the nerves or nerve endings that innervate muscle beneath the skin. Electrical stimulation may be applied superficially on the skin (transcutaneously) or directly into a muscle or muscles (intramuscularly) for the primary purpose of enhancing muscle function. The basic theoretical premise is that if the peripheral nerve can be stimulated, the resulting excitation impulse will be transmitted along the nerve to the motor endplates in the muscle, producing a muscle contraction. In this work, the effect of mere electrical stimulation to the muscle bulk and strength are tested. This paper explains how electrical stimulation can affect the muscle bulk, muscle size, muscle tone, muscle atrophy and muscle strength. The experiment and data collection are performed on 5 subjects and the results obtained are analyzed. This research aims to understand the full potential of electrical stimulation and identifying its possible benefits or disadvantages to the muscle properties. The results indicated that electrical stimulation alone able to improve muscle properties but with certain limits and precautions which might be useful in rehabilitation programme.

Rehabilitation, Using Guided Cerebral Plasticity, of a Brachial Plexus Injury Treated with Intercostal and Phrenic Nerve Transfers.

PubMed

Dahlin, Lars B; Andersson, Gert; Backman, Clas; Svensson, Hampus; Björkman, Anders

2017-01-01

Recovery after surgical reconstruction of a brachial plexus injury using nerve grafting and nerve transfer procedures is a function of peripheral nerve regeneration and cerebral reorganization. A 15-year-old boy, with traumatic avulsion of nerve roots C5-C7 and a non-rupture of C8-T1, was operated 3 weeks after the injury with nerve transfers: (a) terminal part of the accessory nerve to the suprascapular nerve, (b) the second and third intercostal nerves to the axillary nerve, and (c) the fourth to sixth intercostal nerves to the musculocutaneous nerve. A second operation-free contralateral gracilis muscle transfer directly innervated by the phrenic nerve-was done after 2 years due to insufficient recovery of the biceps muscle function. One year later, electromyography showed activation of the biceps muscle essentially with coughing through the intercostal nerves, and of the transferred gracilis muscle by deep breathing through the phrenic nerve. Voluntary flexion of the elbow elicited clear activity in the biceps/gracilis muscles with decreasing activity in intercostal muscles distal to the transferred intercostal nerves (i.e., corresponding to eighth intercostal), indicating cerebral plasticity, where neural control of elbow flexion is gradually separated from control of breathing. To restore voluntary elbow function after nerve transfers, the rehabilitation of patients operated with intercostal nerve transfers should concentrate on transferring coughing function, while patients with phrenic nerve transfers should focus on transferring deep breathing function.

Renal function alterations during skeletal muscle disuse in simulated microgravity

NASA Technical Reports Server (NTRS)

Tucker, Bryan J.

1992-01-01

This project was to examine the alterations in renal functions during skeletal muscle disuse in simulated microgravity. Although this area could cover a wide range of investigative efforts, the limited funding resulted in the selection of two projects. These projects would result in data contributing to an area of research deemed high priority by NASA and would address issues of the alterations in renal response to vasoactive stimuli during conditions of skeletal muscle disuse as well as investigate the contribution of skeletal muscle disuse, conditions normally found in long term human exposure to microgravity, to the balance of fluid and macromolecules within the vasculature versus the interstitium. These two projects selected are as follows: investigate the role of angiotensin 2 on renal function during periods of simulated microgravity and skeletal muscle disuse to determine if the renal response is altered to changes in circulating concentrations of angiotensin 2 compared to appropriate controls; and determine if the shift of fluid balance from vasculature to the interstitium, the two components of extracellular fluid volume, that occur during prolonged exposure to microgravity and skeletal muscle disuse is a result, in part, to alterations in the fluid and macromolecular balance in the peripheral capillary beds, of which the skeletal muscle contains the majority of recruitment capillaries. A recruitment capillary bed would be most sensitive to alterations in Starling forces and fluid and macromolecular permeability.

A regenerative microchannel neural interface for recording from and stimulating peripheral axons in vivo

NASA Astrophysics Data System (ADS)

FitzGerald, James J.; Lago, Natalia; Benmerah, Samia; Serra, Jordi; Watling, Christopher P.; Cameron, Ruth E.; Tarte, Edward; Lacour, Stéphanie P.; McMahon, Stephen B.; Fawcett, James W.

2012-02-01

Neural interfaces are implanted devices that couple the nervous system to electronic circuitry. They are intended for long term use to control assistive technologies such as muscle stimulators or prosthetics that compensate for loss of function due to injury. Here we present a novel design of interface for peripheral nerves. Recording from axons is complicated by the small size of extracellular potentials and the concentration of current flow at nodes of Ranvier. Confining axons to microchannels of ˜100 µm diameter produces amplified potentials that are independent of node position. After implantation of microchannel arrays into rat sciatic nerve, axons regenerated through the channels forming ‘mini-fascicles’, each typically containing ˜100 myelinated fibres and one or more blood vessels. Regenerated motor axons reconnected to distal muscles, as demonstrated by the recovery of an electromyogram and partial prevention of muscle atrophy. Efferent motor potentials and afferent signals evoked by muscle stretch or cutaneous stimulation were easily recorded from the mini-fascicles and were in the range of 35-170 µV. Individual motor units in distal musculature were activated from channels using stimulus currents in the microampere range. Microchannel interfaces are a potential solution for applications such as prosthetic limb control or enhancing recovery after nerve injury.

The effectiveness of a single session of Whole-Body Vibration in improving the balance and the strength in type 2 diabetic patients with mild to moderate degree of peripheral neuropathy: a pilot study.

PubMed

Kordi Yoosefinejad, Amin; Shadmehr, Azadeh; Olyaei, Ghloamreza; Talebian, Saeed; Bagheri, Hossein

2014-01-01

Peripheral neuropathy is a common complication of diabetes mellitus. Muscle strength and the balance deficits are seen in these patients. Whole-Body Vibration (WBV) is a time-efficient method which may be beneficial for them. The immediate effects of WBV on muscle strength and balance have not been studied yet. The aim of this study was to investigate the effects of one session of WBV on muscle strength and the balance of diabetic patients. Ten diabetic patients with peripheral neuropathy took part in this study. Outcome measurements were total strength, strength of tibialis anterior and quadriceps femoris muscles and the balance parameters including Unilateral Stance Test and Timed Up and Go Test. Tibialis anterior muscle strength and Timed Up and GO Test parameters showed significant differences post-exercise in comparison to baseline. A session of WBV had positive effects on muscle strength and the balance in patients with type-2 diabetes associated with neuropathy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Delivery of adipose-derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration.

PubMed

Allbright, Kassandra O; Bliley, Jacqueline M; Havis, Emmanuelle; Kim, Deok-Yeol; Dibernardo, Gabriella A; Grybowski, Damian; Waldner, Matthias; James, Isaac B; Sivak, Wesley N; Rubin, J Peter; Marra, Kacey G

2018-02-06

Peripheral nerve damage is associated with high long-term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose-derived stem cells (ASC) represents a promising therapeutic modality. Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical-sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

Non-elite gymnastics participation is associated with greater bone strength, muscle size, and function in pre- and early pubertal girls.

PubMed

Burt, L A; Naughton, G A; Greene, D A; Courteix, D; Ducher, G

2012-04-01

Recent reports indicate an increase in forearm fractures in children. Bone geometric properties are an important determinant of bone strength and therefore fracture risk. Participation in non-elite gymnastics appears to contribute to improving young girls' musculoskeletal health, more specifically in the upper body. The primary aim of this study was to determine the association between non-elite gymnastics participation and upper limb bone mass, geometry, and strength in addition to muscle size and function in young girls. Eighty-eight pre- and early pubertal girls (30 high-training gymnasts [HGYM, 6-16 hr/ wk], 29 low-training gymnasts [LGYM, 1-5 h r/wk] and 29 non-gymnasts [NONGYM]), aged 6-11 years were recruited. Upper limb lean mass, BMD and BMC were derived from a whole body DXA scan. Forearm volumetric BMD, bone geometry, estimated strength, and muscle CSA were determined using peripheral QCT. Upper body muscle function was investigated with muscle strength, explosive power, and muscle endurance tasks. HGYM showed greater forearm bone strength compared with NGYM, as well as greater arm lean mass, BMC, and muscle function (+5% to +103%, p < 0.05). LGYM displayed greater arm lean mass, BMC, muscle power, and endurance than NGYM (+4% to +46%, p < 0.05); however, the difference in bone strength did not reach significance. Estimated fracture risk at the distal radius, which accounted for body weight, was lower in both groups of gymnasts. Compared with NONGYM, HGYM tended to show larger skeletal differences than LGYM; yet, the two groups of gymnasts only differed for arm lean mass and muscle CSA. Non-elite gymnastics participation was associated with musculoskeletal benefits in upper limb bone geometry, strength and muscle function. Differences between the two gymnastic groups emerged for arm lean mass and muscle CSA, but not for bone strength.

Muscle atrophy in chronic inflammatory demyelinating polyneuropathy: a computed tomography assessment.

PubMed

Ohyama, K; Koike, H; Katsuno, M; Takahashi, M; Hashimoto, R; Kawagashira, Y; Iijima, M; Adachi, H; Watanabe, H; Sobue, G

2014-07-01

Muscle atrophy is generally mild in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) compared with the severity and duration of the muscle weakness. Muscle atrophy was evaluated using computed tomography (CT) in patients with CIDP. Thirty-one patients with typical CIDP who satisfied the diagnostic criteria for the definite CIDP classification proposed by the European Federation of Neurological Societies and the Peripheral Nerve Society were assessed. The clinicopathological findings in patients with muscle atrophy were also compared with those in patients without atrophy. Computed tomography evidence was found of marked muscle atrophy with findings suggestive of fatty degeneration in 11 of the 31 patients with CIDP. CT-assessed muscle atrophy was in the lower extremities, particularly in the ankle plantarflexor muscles. Muscle weakness, which reflects the presence of muscle atrophy, tended to be more pronounced in the lower extremities than in the upper extremities in patients with muscle atrophy, whereas the upper and lower limbs tended to be equally affected in patients without muscle atrophy. Nerve conduction examinations revealed significantly greater reductions in compound muscle action potential amplitudes in the tibial nerves of patients with muscle atrophy. Sural nerve biopsy findings were similar in both groups. The functional prognoses after immunomodulatory therapies were significantly poorer amongst patients with muscle atrophy. Muscle atrophy was present in a subgroup of patients with CIDP, including patients with a typical form of the disease. These patients tended to demonstrate predominant motor impairments of the lower extremities and poorer functional prognoses. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function.

PubMed

Moon, Hyo Youl; Becke, Andreas; Berron, David; Becker, Benjamin; Sah, Nirnath; Benoni, Galit; Janke, Emma; Lubejko, Susan T; Greig, Nigel H; Mattison, Julie A; Duzel, Emrah; van Praag, Henriette

2016-08-09

Peripheral processes that mediate beneficial effects of exercise on the brain remain sparsely explored. Here, we show that a muscle secretory factor, cathepsin B (CTSB) protein, is important for the cognitive and neurogenic benefits of running. Proteomic analysis revealed elevated levels of CTSB in conditioned medium derived from skeletal muscle cell cultures treated with AMP-kinase agonist AICAR. Consistently, running increased CTSB levels in mouse gastrocnemius muscle and plasma. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a mechanism dependent on the multifunctional protein P11. In vivo, in CTSB knockout (KO) mice, running did not enhance adult hippocampal neurogenesis and spatial memory function. Interestingly, in Rhesus monkeys and humans, treadmill exercise elevated CTSB in plasma. In humans, changes in CTSB levels correlated with fitness and hippocampus-dependent memory function. Our findings suggest CTSB as a mediator of effects of exercise on cognition. Published by Elsevier Inc.

Alterations in Skeletal Muscle Microcirculation of Head-Down Tilted Rats

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Stepke, Bernhard; Fleming, John T.; Joshua, Irving G.

1992-01-01

In this study we assessed the function of microscopic blood vessels in skeletal muscle (cremaster muscle) for alterations which may contribute to the observed elevation of blood pressure associated with head-down tilted whole body suspension (HDT/WBS), a model of weightlessness. Arteriolar baseline diameters, vasoconstrictor responses to norepinephrine (NE) and vasodilation to nitroprusside (NP) were assessed in control rats, rats suspended for 7 or 14 day HDT/WBS rats, and rats allowed to recover for 1 day after 7 days HDT/WBS. Neither baseline diameters nor ability to dilate were influenced by HDT/WBS. Maximum vasoconstriction to norepinephrine was significantly greater in arterioles of hypertensive 14 day HDT/WBS rats. This first study of the intact microvasculature in skeletal muscle indicates that an elevated contractility of arterioles to norepinephrine in suspended rats, and suggests an elevated peripheral resistance in striated muscle may contribute to the increase in blood pressures among animals subjected to HDT/WBS.

Investigation of the Expression of Myogenic Transcription Factors, microRNAs and Muscle-Specific E3 Ubiquitin Ligases in the Medial Gastrocnemius and Soleus Muscles following Peripheral Nerve Injury

PubMed Central

Wiberg, Rebecca; Jonsson, Samuel; Novikova, Liudmila N.; Kingham, Paul J.

2015-01-01

Despite surgical innovation, the sensory and motor outcome after a peripheral nerve injury remains incomplete. One contributing factor to the poor outcome is prolonged denervation of the target organ, leading to apoptosis of both mature myofibres and satellite cells with subsequent replacement of the muscle tissue with fibrotic scar and adipose tissue. In this study, we investigated the expression of myogenic transcription factors, muscle specific microRNAs and muscle-specific E3 ubiquitin ligases at several time points following denervation in two different muscles, the gastrocnemius (containing predominantly fast type fibres) and soleus (slow type) muscles, since these molecules may influence the degree of atrophy following denervation. Both muscles exhibited significant atrophy (compared with the contra-lateral sides) at 7 days following either a nerve transection or crush injury. In the crush model, the soleus muscle showed significantly increased muscle weights at days 14 and 28 which was not the case for the gastrocnemius muscle which continued to atrophy. There was a significantly more pronounced up-regulation of MyoD expression in the denervated soleus muscle compared with the gastrocnemius muscle. Conversely, myogenin was more markedly elevated in the gastrocnemius versus soleus muscles. The muscles also showed significantly contrasting transcriptional regulation of the microRNAs miR-1 and miR-206. MuRF1 and Atrogin-1 showed the highest levels of expression in the denervated gastrocnemius muscle. This study provides further insights regarding the intracellular regulatory molecules that generate and maintain distinct patterns of gene expression in different fibre types following peripheral nerve injury. PMID:26691660

Co-Transplantation of Olfactory Ensheathing Cells from Mucosa and Bulb Origin Enhances Functional Recovery after Peripheral Nerve Lesion

PubMed Central

Bon-Mardion, Nicolas; Duclos, Célia; Genty, Damien; Jean, Laetitia; Boyer, Olivier; Marie, Jean-Paul

2011-01-01

Olfactory ensheathing cells (OECs) represent an interesting candidate for cell therapy and could be obtained from olfactory mucosa (OM-OECs) or olfactory bulbs (OB-OECs). Recent reports suggest that, depending on their origin, OECs display different functional properties. We show here the complementary and additive effects of co-transplanting OM-OECs and OB-OECs after lesion of a peripheral nerve. For this, a selective motor denervation of the laryngeal muscles was performed by a section/anastomosis of the recurrent laryngeal nerve (RLN). Two months after surgery, recovery of the laryngeal movements and synkinesis phenonema were analyzed by videolaryngoscopy. To complete these assessments, measure of latency and potential duration were determined by electrophysiological recordings and myelinated nerve fiber profiles were defined based on toluidine blue staining. To explain some of the mechanisms involved, tracking of GFP positive OECs was performed. It appears that transplantation of OM-OECs or OB-OECs displayed opposite abilities to improve functional recovery. Indeed, OM-OECs increased recuperation of laryngeal muscles activities without appropriate functional recovery. In contrast, OB-OECs induced some functional recovery by enhancing axonal regrowth. Importantly, co-transplantation of OM-OECs and OB-OECs supported a major functional recovery, with reduction of synkinesis phenomena. This study is the first which clearly demonstrates the complementary and additive properties of OECs obtained from olfactory mucosa and olfactory bulb to improve functional recovery after transplantation in a nerve lesion model. PMID:21826209

[Peripheral nerve repair: 30 centuries of scientific research].

PubMed

Desouches, C; Alluin, O; Mutaftschiev, N; Dousset, E; Magalon, G; Boucraut, J; Feron, F; Decherchi, P

2005-11-01

Nerve injury compromises sensory and motor functions. Techniques of peripheral nerve repair are based on our knowledge regarding regeneration. Microsurgical techniques introduced in the late 1950s and widely developed for the past 20 years have improved repairs. However, functional recovery following a peripheral mixed nerve injury is still incomplete. Good motor and sensory function after nerve injury depends on the reinnervation of the motor end plates and sensory receptors. Nerve regeneration does not begin if the cell body has not survived the initial injury or if it is unable to initiate regeneration. The regenerated axons must reach and reinnervate the appropriate target end-organs in a timely fashion. Recovery of motor function requires a critical number of motor axons reinnervating the muscle fibers. Sensory recovery is possible if the delay in reinnervation is short. Many additional factors influence the success of nerve repair or reconstruction. The timing of the repair, the level of injury, the extent of the zone of injury, the technical skill of the surgeon, and the method of repair and reconstruction contribute to the functional outcome after nerve injury. This review presents the recent advances in understanding of neural regeneration and their application to the management of primary repairs and nerve gaps.

Protein O-Mannosyltransferases Affect Sensory Axon Wiring and Dynamic Chirality of Body Posture in the Drosophila Embryo.

PubMed

Baker, Ryan; Nakamura, Naosuke; Chandel, Ishita; Howell, Brooke; Lyalin, Dmitry; Panin, Vladislav M

2018-02-14

Genetic defects in protein O-mannosyltransferase 1 (POMT1) and POMT2 underlie severe muscular dystrophies. POMT genes are evolutionarily conserved in metazoan organisms. In Drosophila , both male and female POMT mutants show a clockwise rotation of adult abdominal segments, suggesting a chirality of underlying pathogenic mechanisms. Here we described and analyzed a similar phenotype in POMT mutant embryos that shows left-handed body torsion. Our experiments demonstrated that coordinated muscle contraction waves are associated with asymmetric embryo rolling, unveiling a new chirality marker in Drosophila development. Using genetic and live-imaging approaches, we revealed that the torsion phenotype results from differential rolling and aberrant patterning of peristaltic waves of muscle contractions. Our results demonstrated that peripheral sensory neurons are required for normal contractions that prevent the accumulation of torsion. We found that POMT mutants show abnormal axonal connections of sensory neurons. POMT transgenic expression limited to sensory neurons significantly rescued the torsion phenotype, axonal connectivity defects, and abnormal contractions in POMT mutant embryos. Together, our data suggested that protein O-mannosylation is required for normal sensory feedback to control coordinated muscle contractions and body posture. This mechanism may shed light on analogous functions of POMT genes in mammals and help to elucidate the etiology of neurological defects in muscular dystrophies. SIGNIFICANCE STATEMENT Protein O-mannosyltransferases (POMTs) are evolutionarily conserved in metazoans. Mutations in POMTs cause severe muscular dystrophies associated with pronounced neurological defects. However, neurological functions of POMTs remain poorly understood. We demonstrated that POMT mutations in Drosophila result in abnormal muscle contractions and cause embryo torsion. Our experiments uncovered a chirality of embryo movements and a unique POMT -dependent mechanism that maintains symmetry of a developing system affected by chiral forces. Furthermore, POMTs were found to be required for proper axon connectivity of sensory neurons, suggesting that O-mannosylation regulates the sensory feedback controlling muscle contractions. This novel POMT function in the peripheral nervous system may shed light on analogous functions in mammals and help to elucidate pathomechanisms of neurological abnormalities in muscular dystrophies. Copyright © 2018 the authors 0270-6474/18/381850-16$15.00/0.

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

PubMed

Yan, Yuhui; Shen, Feng-Yi; Agresti, Michael; Zhang, Lin-Ling; Matloub, Hani S; LoGiudice, John A; Havlik, Robert; Li, Jifeng; Gu, Yu-Dong; Yan, Ji-Geng

2017-09-01

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. © 2017 Wiley Periodicals, Inc.

Role of Neurotrophins in the Development and Function of Neural Circuits that Regulate Energy Homeostasis

PubMed Central

Fargali, Samira; Sadahiro, Masato; Jiang, Cheng; Frick, Amy L.; Indall, Tricia; Cogliani, Valeria; Welagen, Jelle; Lin, Wei-jye; Salton, Stephen R.

2012-01-01

Members of the neurotrophin family, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), and other neurotrophic growth factors such as ciliary neurotrophic factor (CNTF) and artemin, regulate peripheral and central nervous system development and function. A subset of the neurotrophin-dependent pathways in the hypothalamus, brainstem, and spinal cord, and those that project via the sympathetic nervous system to peripheral metabolic tissues including brown and white adipose tissue (BAT and WAT), muscle and liver, regulate feeding, energy storage, and energy expenditure. We briefly review the role that neurotrophic growth factors play in energy balance, as regulators of neuronal survival and differentiation, neurogenesis, and circuit formation and function, and as inducers of critical gene products that control energy homeostasis. PMID:22581449

Re-visiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases.

PubMed

Richey, Joyce M; Woolcott, Orison

2017-09-14

The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism. Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects. Consequently, focus has shifted to peripherally restricted cannabinoid 1 (CB1) receptor blockers as possible therapeutic agents that mitigate or eliminate the untoward effects in the central nervous system. Targeting the endocannabinoid system using novel peripheral CB1 receptor blockers with negligible penetrance across the blood-brain barrier may prove to be effective therapy for obesity and its co-morbidities. Perhaps the future of blockers targeting CB1 receptors will be tissue-specific neutral antagonists (e.g., skeletal muscle specific to treat peripheral insulin resistance, adipocyte-specific to treat fat excess, liver-specific to treat fatty liver and hepatic insulin resistance).

Cortical motor activity and reorganization following upper-limb amputation and subsequent targeted reinnervation.

PubMed

Chen, Albert; Yao, Jun; Kuiken, Todd; Dewald, Julius P A

2013-01-01

Previous studies have postulated that the amount of brain reorganization following peripheral injuries may be correlated with negative symptoms or consequences. However, it is unknown whether restoring effective limb function may then be associated with further changes in the expression of this reorganization. Recently, targeted reinnervation (TR), a surgical technique that restores a direct neural connection from amputated sensorimotor nerves to new peripheral targets such as muscle, has been successfully applied to upper-limb amputees. It has been shown to be effective in restoring both peripheral motor and sensory functions via the reinnervated nerves as soon as a few months after the surgery. However, it was unclear whether TR could also restore normal cortical motor representations for control of the missing limb. To answer this question, we used high-density electroencephalography (EEG) to localize cortical activity related to cued motor tasks generated by the intact and missing limb. Using a case study of 3 upper-limb amputees, 2 of whom went through pre and post-TR experiments, we present unique quantitative evidence for the re-mapping of motor representations for the missing limb closer to their original locations following TR. This provides evidence that an effective restoration of peripheral function from TR can be linked to the return of more normal cortical expression for the missing limb. Therefore, cortical mapping may be used as a potential guide for monitoring rehabilitation following peripheral injuries.

Substance P and neurokinin A metabolism by cultured human skeletal muscle myocytes and fibroblasts.

PubMed

Russell, J S; Chi, H; Lantry, L E; Stephens, R E; Ward, P E

1996-01-01

A recent study determined that cultured human skeletal muscle adult myoblasts, myotubes, and fibroblasts degraded angiotensins and kinins via neutral endopeptidase-24.11 (NEP-24.11: EC 3.4.24.11) and aminopeptidase N (APN: EC 3.4.11.2). Due to the possible importance of other peptides to skeletal muscle blood flow and function, the present study looked specifically at the metabolism of the neurokinins substance P (SP) and neurokinin A (NKA) by skeletal muscle peptidases. The results show that SP is degraded not only by NEP-24.11, but also sequentially by dipeptidyl(amino)peptidase IV (DAP IV: EC 3.4.14.5)/APN. NKA is unaffected by DAP IV but is metabolized by NEP-24.11 and APN. NEP-24.11 was inhibited by phosphoramidon (IC50 = 80 nM), thiorphan and ZINCOV, DAP IV by diprotin A (IC50 = 8 microM), and APN by amastatin (IC50 = 50 nM) and bestatin (IC50 = 100 microM). Skeletal muscle myocyte and fibroblast metabolism of SP and NKA may regulate local skeletal muscle vascular and extravascular functions including SP- and NKA-mediated nerve-induced vasodilation. Inhibition of both NEP-24.11 and DAP IV/APN may increase skeletal muscle blood flow and decrease peripheral vascular resistance via potentiation of local neurokinin levels.

Reliability of burst superimposed technique to assess central activation failure during fatiguing contraction.

PubMed

Dousset, Erick; Jammes, Yves

2003-04-01

Recording a superimposed electrically-induced contraction at the limit of endurance during voluntary contraction is used as an indicator of failure of muscle activation by the central nervous system and discards the existence of peripheral muscle fatigue. We questioned on the reliability of this method by using other means to explore peripheral muscle failure. Fifteen normal subjects sustained handgrip at 60% of maximal voluntary contraction (MVC) until exhaustion. During sustained contraction, the power spectrum analysis of the flexor digitorum surface electromyogram allowed us to calculate the leftward shift of median frequency (MF). A superimposed 60 Hz 3 s pulse train (burst superimposition) was delivered to the muscle when force levelled off close to the preset value. Immediately after the fatigue trial had ended, the subject was asked to perform a 5 s 60% MVC and we measured the peak contractile response to a 60 Hz 3 s burst stimulation. Recordings of the compound evoked muscle action potential (M-wave) allowed us to explore an impairment of neuromuscular propagation. A superimposed contraction was measured in 7 subjects in their two forearms, whereas it was absent in the 8 others. Despite these discrepancies, all subjects were able to reproduce a 3 s 60% MVC immediately after the fatigue trial ended and there was no post-fatigue decrease of contraction elicited by the 60 Hz 3 s burst stimulation, as well as no M-wave decrease in amplitude and conduction time. Thus, there was no indication of peripheral muscle fatigue. MF decrease was present in all individuals throughout the fatiguing contraction and it was not correlated with the magnitude of superimposed force. These observations indicate that an absence of superimposed electrically-induced muscle contraction does not allow us to conclude the existence of a sole peripheral muscle fatigue in these circumstances.

The ICM research agenda on intensive care unit-acquired weakness.

PubMed

Latronico, Nicola; Herridge, Margaret; Hopkins, Ramona O; Angus, Derek; Hart, Nicholas; Hermans, Greet; Iwashyna, Theodore; Arabi, Yaseen; Citerio, Giuseppe; Wesley Ely, E; Hall, Jesse; Mehta, Sangeeta; Puntillo, Kathleen; Van den Hoeven, Johannes; Wunsch, Hannah; Cook, Deborah; Dos Santos, Claudia; Rubenfeld, Gordon; Vincent, Jean-Louis; Van den Berghe, Greet; Azoulay, Elie; Needham, Dale M

2017-09-01

We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive state, concurrent illness, frailty, and health trajectories impact outcomes and should be assessed to stratify patients. In the ICU, early assessment of limb and diaphragm muscle strength and function using nonvolitional tests may be useful, but comparison with established methods of global and specific muscle strength and physical function and determination of their reliability and normal values would be important to advance these techniques. Serial measurements of limb and respiratory muscle strength, and systematic screening for dysphagia, would be helpful to clarify if and how weakness of these muscle groups is independently associated with outcome. ICUAW, delirium, and sedatives and analgesics may interact with each other, amplifying the effects of each individual factor. Reduced mobility in patients with hypoactive delirium needs investigations into dysfunction of central and peripheral nervous system motor pathways. Interventional nutritional studies should include muscle mass, strength, and physical function as outcomes, and prioritize elucidation of mechanisms. At follow-up, ICU survivors may suffer from prolonged muscle weakness and wasting and other physical impairments, as well as fatigue without demonstrable weakness on examination. Further studies should evaluate the prevalence and severity of fatigue in ICU survivors and define its association with psychiatric disorders, pain, cognitive impairment, and axonal loss. Finally, methodological issues, including accounting for baseline status, handling of missing data, and inclusion of patient-centered outcome measures should be addressed in future studies.

Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

PubMed

Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

2012-06-20

The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

Mechanical principles of effects of botulinum toxin on muscle length-force characteristics: an assessment by finite element modeling.

PubMed

Turkoglu, Ahu N; Huijing, Peter A; Yucesoy, Can A

2014-05-07

Recent experiments involving muscle force measurements over a range of muscle lengths show that effects of botulinum toxin (BTX) are complex e.g., force reduction varies as a function of muscle length. We hypothesized that altered conditions of sarcomeres within active parts of partially paralyzed muscle is responsible for this effect. Using finite element modeling, the aim was to test this hypothesis and to study principles of how partial activation as a consequence of BTX affects muscle mechanics. In order to model the paralyzing effect of BTX, only 50% of the fascicles (most proximal, or middle, or most distal) of the modeled muscle were activated. For all muscle lengths, a vast majority of sarcomeres of these BTX-cases were at higher lengths than identical sarcomeres of the BTX-free muscle. Due to such "longer sarcomere effect", activated muscle parts show an enhanced potential of active force exertion (up to 14.5%). Therefore, a muscle force reduction originating exclusively from the paralyzed muscle fiber populations, is compromised by the changes of active sarcomeres leading to a smaller net force reduction. Moreover, such "compromise to force reduction" varies as a function of muscle length and is a key determinant of muscle length dependence of force reduction caused by BTX. Due to longer sarcomere effect, muscle optimum length tends to shift to a lower muscle length. Muscle fiber-extracellular matrix interactions occurring via their mutual connections along full peripheral fiber lengths (i.e., myofascial force transmission) are central to these effects. Our results may help improving our understanding of mechanisms of how the toxin secondarily affects the muscle mechanically. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biomarkers of peripheral muscle fatigue during exercise

PubMed Central

2012-01-01

Background Biomarkers of peripheral muscle fatigue (BPMFs) are used to offer insights into mechanisms of exhaustion during exercise in order to detect abnormal fatigue or to detect defective metabolic pathways. This review aims at describing recent advances and future perspectives concerning the most important biomarkers of muscle fatigue during exercise. Results BPMFs are classified according to the mechanism of fatigue related to adenosine-triphosphate-metabolism, acidosis, or oxidative-metabolism. Muscle fatigue is also related to an immunological response. impaired calcium handling, disturbances in bioenergetic pathways, and genetic responses. The immunological and genetic response may make the muscle susceptible to fatigue but may not directly cause muscle fatigue. Production of BPMFs is predominantly dependent on the type of exercise. BPMFs need to change as a function of the process being monitored, be stable without appreciable diurnal variations, correlate well with exercise intensity, and be present in detectable amounts in easily accessible biological fluids. The most well-known BPMFs are serum lactate and interleukin-6. The most widely applied clinical application is screening for defective oxidative metabolism in mitochondrial disorders by means of the lactate stress test. The clinical relevance of most other BPMFs, however, is under debate, since they often depend on age, gender, physical fitness, the energy supply during exercise, the type of exercise needed to produce the BPMF, and whether healthy or diseased subjects are investigated. Conclusions Though the role of BPMFs during fatigue is poorly understood, measuring BPMFs under specific, standardised conditions appears to be helpful for assessing biological states or processes during exercise and fatigue. PMID:23136874

Human enterovirus in the gastrocnemius of patients with peripheral arterial disease.

PubMed

Kim, Julian K S; Zhu, Zhen; Casale, George; Koutakis, Panagiotis; McComb, Rodney D; Swanson, Stanley; Thompson, Jonathan; Miserlis, Dimitrios; Johanning, Jason M; Haynatzki, Gleb; Pipinos, Iraklis I

2013-08-06

Peripheral arterial disease (PAD) is characterized by myofiber degeneration and loss of function in muscles of the lower limbs. Human enterovirus (HEV) infection has been implicated in the pathogenesis of a number of muscle diseases. However, its association with PAD has not been studied. In this study, we tested the hypothesis that infectious HEV is present in skeletal muscle of patients with PAD and is associated with severity of disease. Gastrocnemius biopsies from 37 patients with PAD and 14 controls were examined for the presence of HEV RNA, viral capsid protein, viral RNA copy number, and viral infectivity. HEV RNA was detected in 54% of the biopsies from patients with PAD but was not detected in muscle biopsies from control patients. This difference in prevalence among PAD and control patients was significant at P<0.001. Viral RNA copy numbers were increased significantly at the later stages of disease; Fontaine Stage IV (10(5.50) copies/mg muscle wet weight, at P<0.005) and Stage III (10(4.87) copies/mg, at P<0.010) compared to Stage II (10(2.50) copies/mg). Viral replication was confirmed by the presence of the negative-strand of viral RNA in all specimens positive for HEV RNA. Cultures of HeLa and human skeletal muscle cells treated with muscle homogenates showed HEV replication and the presence of HEV capsid protein. Our data identified infectious HEV in the gastrocnemius of PAD patients but not in controls. Viral copy number and prevalence of infection were higher in the later stages of disease. Our data point to the need for further studies to determine the contribution of HEV infection to the pathophysiology of PAD.

In vivo characterization of regenerative peripheral nerve interface function

NASA Astrophysics Data System (ADS)

Ursu, Daniel C.; Urbanchek, Melanie G.; Nedic, Andrej; Cederna, Paul S.; Gillespie, R. Brent

2016-04-01

Objective. Regenerative peripheral nerve interfaces (RPNIs) are neurotized free autologous muscle grafts equipped with electrodes to record myoelectric signals for prosthesis control. Viability of rat RPNI constructs have been demonstrated using evoked responses. In vivo RPNI characterization is the next critical step for assessment as a control modality for prosthetic devices. Approach. Two RPNIs were created in each of two rats by grafting portions of free muscle to the ends of divided peripheral nerves (peroneal in the left and tibial in the right hind limb) and placing bipolar electrodes on the graft surface. After four months, we examined in vivo electromyographic signal activity and compared these signals to muscular electromyographic signals recorded from autologous muscles in two rats serving as controls. An additional group of two rats in which the autologous muscles were denervated served to quantify cross-talk in the electrode recordings. Recordings were made while rats walked on a treadmill and a motion capture system tracked the hind limbs. Amplitude and periodicity of signals relative to gait were quantified, correlation between electromyographic and motion recording were assessed, and a decoder was trained to predict joint motion. Main Results. Raw RPNI signals were active during walking, with amplitudes of 1 mVPP, and quiet during standing, with amplitudes less than 0.1 mVPP. RPNI signals were periodic and entrained with gait. A decoder predicted bilateral ankle motion with greater than 80% reliability. Control group signal activity agreed with literature. Denervated group signals remained quiescent throughout all evaluations. Significance. In vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Signal contamination from muscles adjacent to the RPNI is minimal, as demonstrated by the low amplitude signals obtained from the Denervated group. The periodicity and entrainment to gait of RPNI recordings suggests the transduced signals were generated via central nervous system control.

Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease.

PubMed

Fuld, J P; Kilduff, L P; Neder, J A; Pitsiladis, Y; Lean, M E J; Ward, S A; Cotton, M M

2005-07-01

Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease (COPD). Creatine nutritional supplementation produces increased muscle mass and exercise performance in health. A controlled study was performed to look for similar effects in 38 patients with COPD. Thirty eight patients with COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 46 (15)% predicted) were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2 weeks loading (one dose three times daily), patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance (once daily) supplementation. Pulmonary function, body composition, and exercise performance (peripheral muscle strength and endurance, shuttle walking, cycle ergometry) took place at baseline (n = 38), post loading (n = 36), and post rehabilitation (n = 25). No difference was found in whole body exercise performance between the groups: for example, incremental shuttle walk distance mean -23.1 m (95% CI -71.7 to 25.5) post loading and -21.5 m (95% CI -90.6 to 47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI 0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation. Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI 1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI 131.3 to 1577.4) post rehabilitation. Creatine improved health status between baseline and post rehabilitation (St George's Respiratory Questionnaire total score -7.7 (95% CI -14.9 to -0.5)). Creatine supplementation led to increases in fat-free mass, peripheral muscle strength and endurance, health status, but not exercise capacity. Creatine may constitute a new ergogenic treatment in COPD.

Long-term recovery of muscle strength after denervation in the fibular division of the sciatic nerve.

PubMed

Stefancic, Martin; Vidmar, Gaj; Blagus, Rok

2016-10-01

The probability and degree of muscle recovery after lesions of long peripheral nerves have not been assessed quantitatively. Twelve adults with closed injuries of the fibular division of the sciatic nerve with complete denervation of associated muscles were followed-up for 2-10 years. The onset of reinnervation was detected electromyographically. Calf circumference and maximum voluntary isometric contraction (MVIC) of foot dorsiflexion were measured on both sides during 2-4 visits. Reinnervation occurred in 11 patients after an average of 13 months. MVIC on the affected side was 2%-27% of that on the unaffected side (average 11%) and remained stable for the following 2-3 years. Correlations and mixed-model regressions confirmed that the degree of recovery was negatively associated with duration of denervation. Reinnervation occurs in about 90% of patients within about 1 year. About 10% of baseline dorsiflexion strength is permanently recovered, which is functionally relevant. Muscle Nerve, 2016 Muscle Nerve 54: -, 2016 Muscle Nerve 54: 702-708, 2016. © 2016 Wiley Periodicals, Inc.

Central and peripheral fatigue in knee and elbow extensor muscles after a long-distance cross-country ski race.

PubMed

Boccia, G; Dardanello, D; Zoppirolli, C; Bortolan, L; Cescon, C; Schneebeli, A; Vernillo, G; Schena, F; Rainoldi, A; Pellegrini, B

2017-09-01

Although elbow extensors (EE) have a great role in cross-country skiing (XC) propulsion, previous studies on neuromuscular fatigue in long-distance XC have investigated only knee extensor (KE) muscles. In order to investigate the origin and effects of fatigue induced by long-distance XC race, 16 well-trained XC skiers were tested before and after a 56-km classical technique race. Maximal voluntary isometric contraction (MVC) and rate of force development (RFD) were measured for both KE and EE. Furthermore, electrically evoked double twitch during MVC and at rest were measured. MVC decreased more in KE (-13%) than in EE (-6%, P = 0.016), whereas the peak RFD decreased only in EE (-26%, P = 0.02) but not in KE. The two muscles showed similar decrease in voluntary activation (KE -5.0%, EE -4.8%, P = 0.61) and of double twitch amplitude (KE -5%, EE -6%, P = 0.44). A long-distance XC race differently affected the neuromuscular function of lower and upper limbs muscles. Specifically, although the strength loss was greater for lower limbs, the capacity to produce force in short time was more affected in the upper limbs. Nevertheless, both KE and EE showed central and peripheral fatigue, suggesting that the origins of the strength impairments were multifactorial for the two muscles. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.

PubMed

Archibald, S J; Krarup, C; Shefner, J; Li, S T; Madison, R D

1991-04-22

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS)

SMASH - semi-automatic muscle analysis using segmentation of histology: a MATLAB application.

PubMed

Smith, Lucas R; Barton, Elisabeth R

2014-01-01

Histological assessment of skeletal muscle tissue is commonly applied to many areas of skeletal muscle physiological research. Histological parameters including fiber distribution, fiber type, centrally nucleated fibers, and capillary density are all frequently quantified measures of skeletal muscle. These parameters reflect functional properties of muscle and undergo adaptation in many muscle diseases and injuries. While standard operating procedures have been developed to guide analysis of many of these parameters, the software to freely, efficiently, and consistently analyze them is not readily available. In order to provide this service to the muscle research community we developed an open source MATLAB script to analyze immunofluorescent muscle sections incorporating user controls for muscle histological analysis. The software consists of multiple functions designed to provide tools for the analysis selected. Initial segmentation and fiber filter functions segment the image and remove non-fiber elements based on user-defined parameters to create a fiber mask. Establishing parameters set by the user, the software outputs data on fiber size and type, centrally nucleated fibers, and other structures. These functions were evaluated on stained soleus muscle sections from 1-year-old wild-type and mdx mice, a model of Duchenne muscular dystrophy. In accordance with previously published data, fiber size was not different between groups, but mdx muscles had much higher fiber size variability. The mdx muscle had a significantly greater proportion of type I fibers, but type I fibers did not change in size relative to type II fibers. Centrally nucleated fibers were highly prevalent in mdx muscle and were significantly larger than peripherally nucleated fibers. The MATLAB code described and provided along with this manuscript is designed for image processing of skeletal muscle immunofluorescent histological sections. The program allows for semi-automated fiber detection along with user correction. The output of the code provides data in accordance with established standards of practice. The results of the program have been validated using a small set of wild-type and mdx muscle sections. This program is the first freely available and open source image processing program designed to automate analysis of skeletal muscle histological sections.

Study on the Effect of Thermal and Magnetic Stimulation by Measuring of the Peripheral Blood Flow and Skin Temperature

NASA Astrophysics Data System (ADS)

Kubota, Kouhei; Nuruki, Atsuo; Tamari, Youzou; Yunokuchi, Kazutomo

Recently, the stiff shoulder accompanying the muscle fatigue becomes an issue of public concern. Therefore, we paid attention to the effect of the thermal and magnetic stimulation for the muscle fatigue. The maximum voluntary contraction has recovered significantly, and also peripheral blood flow has increased by stimulation. In order to evaluate if the thermal and magnetic stimulation has any effects, three parameters was measured, which are the maximum voluntary contraction, peripheral blood flow and skin temperature. The skin temperature, however, did not changed significantly.

Neurotized lateral gastrocnemius muscle transfer for persistent traumatic peroneal nerve palsy: Surgical technique.

PubMed

Leclère, F M; Badur, N; Mathys, L; Vögelin, E

2015-08-01

Persistent traumatic peroneal nerve palsy, following nerve surgery failure, is usually treated by tendon transfer or more recently by tibial nerve transfer. However, when there is destruction of the tibial anterior muscle, an isolated nerve transfer is not possible. In this article, we present the key steps and surgical tips for the Ninkovic procedure including transposition of the neurotized lateral gastrocnemius muscle with the aim of restoring active voluntary dorsiflexion. The transposition of the lateral head of the gastrocnemius muscle to the tendons of the anterior tibial muscle group, with simultaneous transposition of the intact proximal end of the deep peroneal nerve to the tibial nerve of the gastrocnemius muscle by microsurgical neurorrhaphy is performed in one stage. It includes 10 key steps which are described in this article. Since 1994, three clinical series have highlighted the advantages of this technique. Functional and subjective results are discussed. We review the indications and limitations of the technique. Early clinical results after neurotized lateral gastrocnemius muscle transfer appear excellent; however, they still need to be compared with conventional tendon transfer procedures. Clinical studies are likely to be conducted in this area largely due to the frequency of persistant peroneal nerve palsy and the limitations of functional options in cases of longstanding peripheral nerve palsy, anterior tibial muscle atrophy or destruction. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Exercise capacity, muscle strength and fatigue in sarcoidosis.

PubMed

Marcellis, R G J; Lenssen, A F; Elfferich, M D P; De Vries, J; Kassim, S; Foerster, K; Drent, M

2011-09-01

The aim of this case-control study was to investigate the prevalence of exercise intolerance, muscle weakness and fatigue in sarcoidosis patients. Additionally, we evaluated whether fatigue can be explained by exercise capacity, muscle strength or other clinical characteristics (lung function tests, radiographic stages, prednisone usage and inflammatory markers). 124 sarcoidosis patients (80 males) referred to the Maastricht University Medical Centre (Maastricht, the Netherlands) were included (mean age 46.6±10.2 yrs). Patients performed a 6-min walk test (6MWT) and handgrip force (HGF), elbow flexor muscle strength (EFMS), quadriceps peak torque (QPT) and hamstring peak torque (HPT) tests. Maximal inspiratory pressure (P(I,max)) was recorded. All patients completed the Fatigue Assessment Scale (FAS) questionnaire. The 6MWT was reduced in 45% of the population, while HGF, EFMS, QPT and HPT muscle strength were reduced in 15, 12, 27 and 18%, respectively. P(I,max) was reduced in 43% of the population. The majority of the patients (81%) reported fatigue (FAS ≥22). Patients with reduced peripheral muscle strength of the upper and/or lower extremities were more fatigued and demonstrated impaired lung functions, fat-free mass, P(I,max), 6MWT and quality of life. Fatigue was neither predicted by exercise capacity, nor by muscle strength. Besides fatigue, exercise intolerance and muscle weakness are frequent problems in sarcoidosis. We therefore recommend physical tests in the multidisciplinary management of sarcoidosis patients, even in nonfatigued patients.

ELECTROMYOGRAPHIC ACTIVITY OF STERNOCLEIDOMASTOID AND MASTICATORY MUSCLES IN PATIENTS WITH VESTIBULAR LESIONS

PubMed Central

Tartaglia, Gianluca M.; Barozzi, Stefania; Marin, Federico; Cesarani, Antonio; Ferrario, Virgilio F.

2008-01-01

This study evaluated the electromyographic characteristics of masticatory and neck muscles in subjects with vestibular lesions. Surface electromyography of the masseter, temporalis and sternocleidomastoid muscles was performed in 19 patients with Ménière's disease, 12 patients with an acute peripheral vestibular lesion, and 19 control subjects matched for sex and age. During maximum voluntary clenching, patients with peripheral vestibular lesions had the highest co-contraction of the sternocleidomastoid muscle (analysis of covariance, p=0.02), the control subjects had the smallest values, and the patients with Ménière's disease had intermediate values. The control subjects had larger standardized muscle activities than the other patient groups (p=0.001). In conclusion, during maximum voluntary tooth clenching, patients with vestibular alterations have both more active neck muscles, and less active masticatory muscles than normal controls. Results underline the importance of a more inclusive craniocervical assessment of patients with vestibular lesions. PMID:19082397

Direct current electrical stimulation of acupuncture needles for peripheral nerve regeneration: an exploratory case series.

PubMed

Inoue, Motohiro; Katsumi, Yasukazu; Itoi, Megumi; Hojo, Tatsuya; Nakajima, Miwa; Ohashi, Suzuyo; Oi, Yuki; Kitakoji, Hiroshi

2011-06-01

To examine the therapeutic effect of a novel therapeutic method based on electroacupuncture with intermittent direct current (DCEA) and associated adverse events in patients with peripheral nerve damage and a poor clinical prognosis. In seven older patients with peripheral nerve damage (neurapraxia 2, axonotmesis 4, neuromesis 1), an acupuncture needle connected to an anode electrode was inserted proximal to the site of the injury along the route of the nerve, while the cathode electrode was inserted into the innervated muscle, and DCEA was performed (100 Hz for 20 min, weekly). Muscular paralysis was evaluated weekly with manual muscle testing, the active range of motion of joints related to the muscular paralysis and, when necessary, needle electromyography. Adverse events were also recorded during the course of the treatment. Complete functional recovery was observed in the two cases with neurapraxia and two with axonotmesis, while one axonotmesis case achieved improvement and the other showed reinnervation potential without functional recovery. No improvement was observed in the neurotmesis case. Pigmentation of the skin where the anode needle was inserted occurred in three cases. Although there was no definite causal link, one case showed excessive formation and resorption of bone in the area close to the cathode needle site. Accelerated nerve regeneration caused by DCEA may contribute to recovery. The skin pigmentation and callus formation suggest that the shape of the anode electrode, current intensity and other factors should be examined to establish a safer treatment method.

A 3D-engineered porous conduit for peripheral nerve repair

PubMed Central

Tao, Jie; Hu, Yu; Wang, Shujuan; Zhang, Jiumeng; Liu, Xuan; Gou, Zhiyuan; Cheng, Hao; Liu, Qianqi; Zhang, Qianqian; You, Shenglan; Gou, Maling

2017-01-01

End-to-end neurorrhaphy is the most commonly used method for treating peripheral nerve injury. However, only 50% of patients can regain useful function after treating with neurorrhaphy. Here, we constructed a 3D-engineered porous conduit to promote the function recovery of the transected peripheral nerve after neurorrhaphy. The conduit that consisted of a gelatin cryogel was prepared by molding with 3D-printed moulds. Due to its porous structure and excellent mechanical properties, this conduit could be collapsed by the mechanical force and resumed its original shape after absorption of normal saline. This shape-memory property allowed a simply surgery process for installing the conduits. Moreover, the biodegradable conduit could prevent the infiltration of fibroblasts and reduce the risk of scar tissue, which could provide an advantageous environment for nerve regeneration. The efficiency of the conduits in assisting peripheral nerve regeneration after neurorrhaphy was evaluated in a rat sciatic nerve transected model. Results indicated that conduits significantly benefitted the recovery of the transected peripheral nerve after end-to-end neurorrhaphy on the static sciatic index (SSI), electrophysiological results and the re-innervation of the gastrocnemius muscle. This work demonstrates a biodegradable nerve conduit that has potentially clinical application in promoting the neurorrhaphy. PMID:28401914

Functional rescue of dystrophin-deficient mdx mice by a chimeric peptide-PMO.

PubMed

Yin, Haifang; Moulton, Hong M; Betts, Corinne; Merritt, Thomas; Seow, Yiqi; Ashraf, Shirin; Wang, Qingsong; Boutilier, Jordan; Wood, Matthew Ja

2010-10-01

Splice modulation using antisense oligonucleotides (AOs) has been shown to yield targeted exon exclusion to restore the open reading frame and generate truncated but partially functional dystrophin protein. This has been successfully demonstrated in dystrophin-deficient mdx mice and in Duchenne muscular dystrophy (DMD) patients. However, DMD is a systemic disease; successful therapeutic exploitation of this approach will therefore depend on effective systemic delivery of AOs to all affected tissues. We have previously shown the potential of a muscle-specific/arginine-rich chimeric peptide-phosphorodiamidate morpholino (PMO) conjugate, but its long-term activity, optimized dosing regimen, capacity for functional correction and safety profile remain to be established. Here, we report the results of this chimeric peptide-PMO conjugate in the mdx mouse using low doses (3 and 6 mg/kg) administered via a 6 biweekly systemic intravenous injection protocol. We show 100% dystrophin-positive fibers and near complete correction of the dystrophin transcript defect in all peripheral muscle groups, with restoration of 50% dystrophin protein over 12 weeks, leading to correction of the DMD pathological phenotype and restoration of muscle function in the absence of detectable toxicity or immune response. Chimeric muscle-specific/cell-penetrating peptides therefore represent highly promising agents for systemic delivery of splice-correcting PMO oligomers for DMD therapy.

Relationship between PPARα mRNA expression and mitochondrial respiratory function and ultrastructure of the skeletal muscle of patients with COPD.

PubMed

Zhang, Jian-Qing; Long, Xiang-Yu; Xie, Yu; Zhao, Zhi-Huan; Fang, Li-Zhou; Liu, Ling; Fu, Wei-Ping; Shu, Jing-Kui; Wu, Jiang-Hai; Dai, Lu-Ming

2017-11-02

Peripheral muscle dysfunction is an important complication in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to explore the relationship between the levels of peroxisome proliferator-activated receptor α (PPARα) mRNA expression and the respiratory function and ultrastructure of mitochondria in the vastus lateralis of patients with COPD. Vastus lateralis biopsies were performed on 14 patients with COPD and 6 control subjects with normal lung function. PPARα mRNA levels in the muscle tissue were detected by real-time PCR. A Clark oxygen electrode was used to assess mitochondrial respiratory function. Mitochondrial number, fractional area in skeletal muscle cross-sections, and Z-line width were observed via transmission electron microscopy. The PPARα mRNA expression was significantly lower in COPD patients with low body mass index (BMIL) than in both COPD patients with normal body mass index (BMIN) and controls. Mitochondrial respiratory function (assessed by respiratory control ratio) was impaired in COPD patients, particularly in BMIL. Compared with that in the control group, mitochondrial number and fractional area were lower in the BMIL group, but were maintained in the BMIN group. Further, the Z-line became narrow in the BMIL group. PPARα mRNA expression was positively related to mitochondrial respiratory function and volume density. In COPD patients with BMIN, mitochondria volume density was maintained, while respiratory function decreased, whereas both volume density and respiratory function decreased in COPD patients with BMIL. PPARα mRNA expression levels are associated with decreased mitochondrial respiratory function and volume density, which may contribute to muscle dysfunction in COPD patients.

Influence of blood flow occlusion on the development of peripheral and central fatigue during small muscle mass handgrip exercise

PubMed Central

Broxterman, R M; Craig, J C; Smith, J R; Wilcox, S L; Jia, C; Warren, S; Barstow, T J

2015-01-01

Abstract The influence of the muscle metabolic milieu on peripheral and central fatigue is currently unclear. Moreover, the relationships between peripheral and central fatigue and the curvature constant (W ′) have not been investigated. Six men (age: 25 ± 4 years, body mass: 82 ± 10 kg, height: 179 ± 4 cm) completed four constant power handgrip tests to exhaustion under conditions of control exercise (Con), blood flow occlusion exercise (Occ), Con with 5 min post-exercise blood flow occlusion (Con + Occ), and Occ with 5 min post-exercise blood flow occlusion (Occ + Occ). Neuromuscular fatigue measurements and W ′ were obtained for each subject. Each trial resulted in significant peripheral and central fatigue. Significantly greater peripheral (79.7 ± 5.1% vs. 22.7 ± 6.0%) and central (42.6 ± 3.9% vs. 4.9 ± 2.0%) fatigue occurred for Occ than for Con. In addition, significantly greater peripheral (83.0 ± 4.2% vs. 69.0 ± 6.2%) and central (65.5 ± 14.6% vs. 18.6 ± 4.1%) fatigue occurred for Occ + Occ than for Con + Occ. W ′ was significantly related to the magnitude of global (r = 0.91) and peripheral (r = 0.83) fatigue. The current findings demonstrate that blood flow occlusion exacerbated the development of both peripheral and central fatigue and that post-exercise blood flow occlusion prevented the recovery of both peripheral and central fatigue. Moreover, the current findings suggest that W ′ may be determined by the magnitude of fatigue accrued during exercise. Key points Critical power represents an important threshold for neuromuscular fatigue development and may, therefore, dictate intensities for which exercise tolerance is determined by the magnitude of fatigue accrued. Peripheral fatigue appears to be constant across O2 delivery conditions for large muscle mass exercise, but this consistency is equivocal for smaller muscle mass exercise. We sought to determine the influence of blood flow occlusion during handgrip exercise on neuromuscular fatigue development and to examine the relationship between neuromuscular fatigue development and W ′. Blood flow occlusion influenced the development of both peripheral and central fatigue, thus providing further evidence that the magnitude of peripheral fatigue is not constant across O2 delivery conditions for small muscle mass exercise. W ′ appears to be related to the magnitude of fatigue accrued during exercise, which may explain the reported consistency of intramuscular metabolic perturbations and work performed for severe-intensity exercise. PMID:26104881

Electrical stimulation as a means for achieving recovery of function in stroke patients.

PubMed

Popović, Dejan B; Sinkaer, Thomas; Popović, Mirjana B

2009-01-01

This review presents technologies used in and assesses the main clinical outcomes of electrical therapies designed to speed up and increase functional recovery in stroke patients. The review describes methods which interface peripheral systems (e.g., cyclic neural stimulation, stimulation triggered by electrical activity of muscles, therapeutic functional electrical stimulation) and transcranial brain stimulation with surface and implantable electrodes. Our conclusion from reviewing these data is that integration of electrical therapy into exercise-active movement mediated by electrical activation of peripheral and central sensory-motor mechanisms enhances motor re-learning following damage to the central nervous system. Motor re-learning is considered here as a set of processes associated with practice or experience that leads to long-term changes in the capability for movement. An important suggestion is that therapeutic effects are likely to be much more effective when treatment is applied in the acute, rather than in the chronic, phase of stroke.

The ventilated patient undergoing hydrotherapy: a case study.

PubMed

Taylor, Susan

2003-08-01

The ascending peripheral neuropathy and paralysis that result from Guillain-Barre Syndrome's (GBS) demyelination of peripheral nerves is a challenge to health professionals; the patient requires support during the acute disease process and during the remyelination recovery period, often lasting months to years. The staff of a major metropolitan teaching hospital's critical care unit (CCU) and physiotherapy departments developed a hydrotherapy treatment programme for a ventilated patient with GBS. Through careful planning and appropriate preparation, it was found that hydrotherapy could successfully and safely be incorporated into a patient's treatment regimen. The benefits included improved range of movement due to the supportive nature of water, anecdotal increased strength, size and movement of remyelinating muscles and a psychological improvement. Although this patient has not recovered from GBS to be independent, hydrotherapy was a valuable part of the treatment regimen and it could be suggested the increase muscle strength lead to improved respiratory function and enabled weaning from ventilation, reducing intensive care length of stay and cost.

Msx1 and Msx2 are expressed in sub-populations of vascular smooth muscle cells.

PubMed

Goupille, Olivier; Saint Cloment, Cécile; Lopes, Miguel; Montarras, Didier; Robert, Benoît

2008-08-01

Using an nlacZ reporter gene inserted at the Msx1 and Msx2 loci, we could analyze the expression of these homeogenes in the adult mouse. We observed that Msx genes are prominently expressed in a subset of blood vessels. The Msx2nlacZ allele is mainly expressed in a restricted population of mural cells in peripheral arteries and veins. Msx1nlacZ is expressed to a lesser extent by vascular smooth muscle cells of peripheral arteries, but is highly expressed in arterioles and capillaries, making Msx1 a novel marker for a subpopulation of pericytes. Expression is set up early in developing vessels and maintained throughout life. In addition, expression of both genes is observed in a few endothelial cells of the aorta at fetal stages, and only Msx2 continues to be expressed in this layer at the adult stage. These results suggest major functions for Msx genes in vascular mural cell formation and remodeling. Copyright (c) 2008 Wiley-Liss, Inc.

Nerve Transfers to Restore Shoulder Function.

PubMed

Leechavengvongs, Somsak; Malungpaishorpe, Kanchai; Uerpairojkit, Chairoj; Ng, Chye Yew; Witoonchart, Kiat

2016-05-01

The restoration of shoulder function after brachial plexus injury represents a significant challenge facing the peripheral nerve surgeons. This is owing to a combination of the complex biomechanics of the shoulder girdle, the multitude of muscles and nerves that could be potentially injured, and a limited number of donor options. In general, nerve transfer is favored over tendon transfer, because the biomechanics of the musculotendinous units are not altered. This article summarizes the surgical techniques and clinical results of nerve transfers for restoration of shoulder function. Copyright © 2016 Elsevier Inc. All rights reserved.

The fusimotor and reafferent origin of the sense of force and weight

PubMed Central

Luu, Billy L; Day, Brian L; Cole, Jonathan D; Fitzpatrick, Richard C

2011-01-01

Abstract Signals associated with the command the brain sends to muscles are thought to create the sensation of heaviness when we lift an object. Thus, as a muscle is weakened by fatigue or partial paralysis (neuromuscular blockade), the increase in the motor command needed to lift a weight is thought to explain the increasing subjective heaviness of the lifted object. With different fatiguing contractions we approximately halved the force output of the thumb flexor muscles, which were then used to lift an object. For two deafferented subjects the perceived heaviness of the lifted object approximately doubled, in keeping with the central-signal theory. However, for normal subjects this resulted in objects feeling the same or lighter, inconsistent with the central-signal theory but consistent with the expected effects of the conditioning contractions on the sensitivity of peripheral receptors. In separate experiments we subjected the forearm muscles to complete paralysis with a non-depolarising neuromuscular blocking agent and then allowed them to recover to approximately half-force output. This also resulted in objects feeling lighter when lifted by the semi-paralysed thumb, even though the motor command to the motoneurons must have been greater. This is readily explained by reduced lift-related reafference caused by the prolonged paralysis of muscle spindle intrafusal fibres. We conclude that peripheral signals, including a major contribution from muscle spindles, normally give rise to the sense of exerted force. In concept, however, reafference from peripheral receptors may also be considered a centrally generated signal that traverses efferent and then afferent pathways to feed perceptual centres rather than one confined entirely to the central nervous system. These results therefore challenge the distinction between central- and peripheral-based perception, and the concept that muscle spindles provide only information about limb position and movement. PMID:21521756

Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats.

PubMed

Mikesh, Michelle; Ghergherehchi, Cameron L; Rahesh, Sina; Jagannath, Karthik; Ali, Amir; Sengelaub, Dale R; Trevino, Richard C; Jackson, David M; Tucker, Haley O; Bittner, George D

2018-07-01

Many publications report that ablations of segments of peripheral nerves produce the following unfortunate results: (1) Immediate loss of sensory signaling and motor control; (2) rapid Wallerian degeneration of severed distal axons within days; (3) muscle atrophy within weeks; (4) poor behavioral (functional) recovery after many months, if ever, by slowly-regenerating (∼1mm/d) axon outgrowths from surviving proximal nerve stumps; and (5) Nerve allografts to repair gap injuries are rejected, often even if tissue matched and immunosuppressed. In contrast, using a female rat sciatic nerve model system, we report that neurorrhaphy of allografts plus a well-specified-sequence of solutions (one containing polyethylene glycol: PEG) successfully addresses each of these problems by: (a) Reestablishing axonal continuity/signaling within minutes by nonspecific ally PEG-fusing (connecting) severed motor and sensory axons across each anastomosis; (b) preventing Wallerian degeneration by maintaining many distal segments of inappropriately-reconnected, PEG-fused axons that continuously activate nerve-muscle junctions; (c) maintaining innervation of muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; (d) inducing remarkable behavioral recovery to near-unoperated levels within days to weeks, almost certainly by CNS and PNS plasticities well-beyond what most neuroscientists currently imagine; and (e) preventing rejection of PEG-fused donor nerve allografts with no tissue matching or immunosuppression. Similar behavioral results are produced by PEG-fused autografts. All results for Negative Control allografts agree with current neuroscience data 1-5 given above. Hence, PEG-fusion of allografts for repair of ablated peripheral nerve segments expand on previous observations in single-cut injuries, provoke reconsideration of some current neuroscience dogma, and further extend the potential of PEG-fusion in clinical practice. © 2018 Wiley Periodicals, Inc.

Estimating Isometric Tension of Finger Muscle Using Needle EMG Signals and the Twitch Contraction Model

NASA Astrophysics Data System (ADS)

Tachibana, Hideyuki; Suzuki, Takafumi; Mabuchi, Kunihiko

We address an estimation method of isometric muscle tension of fingers, as fundamental research for a neural signal-based prosthesis of fingers. We utilize needle electromyogram (EMG) signals, which have approximately equivalent information to peripheral neural signals. The estimating algorithm comprised two convolution operations. The first convolution is between normal distribution and a spike array, which is detected by needle EMG signals. The convolution estimates the probability density of spike-invoking time in the muscle. In this convolution, we hypothesize that each motor unit in a muscle activates spikes independently based on a same probability density function. The second convolution is between the result of the previous convolution and isometric twitch, viz., the impulse response of the motor unit. The result of the calculation is the sum of all estimated tensions of whole muscle fibers, i.e., muscle tension. We confirmed that there is good correlation between the estimated tension of the muscle and the actual tension, with >0.9 correlation coefficients at 59%, and >0.8 at 89% of all trials.

Impact of placental insufficiency on fetal skeletal muscle growth

PubMed Central

Hay, William W.

2016-01-01

Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal “catch-up” growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. PMID:26994511

Transient visual responses reset the phase of low-frequency oscillations in the skeletomotor periphery.

PubMed

Wood, Daniel K; Gu, Chao; Corneil, Brian D; Gribble, Paul L; Goodale, Melvyn A

2015-08-01

We recorded muscle activity from an upper limb muscle while human subjects reached towards peripheral targets. We tested the hypothesis that the transient visual response sweeps not only through the central nervous system, but also through the peripheral nervous system. Like the transient visual response in the central nervous system, stimulus-locked muscle responses (< 100 ms) were sensitive to stimulus contrast, and were temporally and spatially dissociable from voluntary orienting activity. Also, the arrival of visual responses reduced the variability of muscle activity by resetting the phase of ongoing low-frequency oscillations. This latter finding critically extends the emerging evidence that the feedforward visual sweep reduces neural variability via phase resetting. We conclude that, when sensory information is relevant to a particular effector, detailed information about the sensorimotor transformation, even from the earliest stages, is found in the peripheral nervous system. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise

PubMed Central

Gordon, Tessa; English, Arthur W.

2015-01-01

Enhancing the regeneration of axons is often considered a therapeutic target for improving functional recovery after peripheral nerve injury. In this review, the evidence for the efficacy of electrical stimulation (ES), daily exercise, and their combination in promoting nerve regeneration after peripheral nerve injuries in both animal models and in human patients, is explored. The rationale, effectiveness, and molecular basis of ES and exercise in accelerating axon outgrowth are reviewed. In comparing the effects of ES and exercise in enhancing axon regeneration, increased neural activity, neurotrophins, and androgens are considered common requirements. Similar, gender-specific requirements are found for exercise to enhance axon regeneration in the periphery and for sustaining synaptic inputs onto injured motoneurons. ES promotes nerve regeneration after delayed nerve repair in humans and rats. The effectiveness of exercise is less clear. Although ES, but not exercise, results in a significant misdirection of regenerating motor axons to reinnervate different muscle targets, the loss of neuromuscular specificity encountered has only a very small impact on resulting functional recovery. Both ES and exercise are promising experimental treatments for peripheral nerve injury that seem ready to be translated to clinical use. PMID:26121368

Functioning of peripheral Ia pathways in infants with typical development: responses in antagonist muscle pairs

PubMed Central

Ulrich, Beverly D.; Martin, Bernard

2015-01-01

In muscle responses of proprioceptive origin, including the stretch/tendon reflex (T-reflex), the corresponding reciprocal excitation and irradiation to distant muscles have been described from newborn infants to older adults. However, the functioning of other responses mediated primarily by Ia-afferents has not been investigated in infants. Understanding the typical development of these multiple pathways is critical to determining potential problems in their development in populations affected by neurological disease, such as spina bifida or cerebral palsy. Hence, the goal of the present study was to quantify the excitability of Ia-mediated responses in lower limb muscles of infants with typical development. These responses were elicited by mechanical stimulation applied to the distal tendons of the gastrocnemius-soleus (GS), tibialis anterior (TA) and quadriceps (QAD) muscles of both legs in twelve 2- to 10-month-old infants and recorded simultaneously in antagonist muscle pairs by surface EMG. Tendon taps alone elicited responses in either, both or neither muscle. The homonymous response (T-reflex) was less frequent in the TA than the GS or QAD muscle. An 80 Hz vibration superimposed on tendon taps induced primarily an inhibition of monosynaptic responses; however, facilitation also occurred in either muscle of the recorded pair. These responses were not influenced significantly by age or gender. Vibration alone produced a tonic reflex response in the vibrated muscle (TVR) and/or the antagonist muscle (AVR). However, for the TA muscle the TVR was more frequently elicited in older than younger infants. High variability was common to all responses. Overall, the random distribution and inconsistency of muscle responses suggests that the gain of Ia-mediated feedback is unstable. We propose that during infancy the central nervous system needs to learn to set stable feedback gain, or destination of proprioceptive assistance, based on their use during functional movements. This will tailor the neuromuscular connectivity to support adaptive motor behaviors. PMID:21140137

Afferent control mechanisms involved in the development of soleus fiber alterations in simulated hypogravity

NASA Astrophysics Data System (ADS)

Shenkman, B. S.; Nemirovskaya, T. L.; Shapovalova, K. B.; Podlubnaya, Z. A.; Vikhliantsev, I. M.; Moukhina, A. M.; Kozlovskaya, I. B.

2007-02-01

It was recently established that support withdrawal (withdrawal of support reaction force) in microgravity provokes a sequence of functional shifts in the activity of motor units (inactivation of slow ones) and peripheral muscle apparatus which lead to the decline of postural muscle contractility and alterations in fiber characteristics. However, mechanisms involved in inactivation of the slow motor units and appropriate slow-twitch muscle fiber disuse under the supportless conditions remained unknown. We show here that artificial inactivation of muscles-antagonists (which are known to be hyperactive during unloading) counteracts some of the unloading-induced events in the rat soleus (fiber size reduction, slow-to-fast fiber-type transition and decline of titin and nebulin content). It was also demonstrated that direct activation of the muscarinic receptors of the neostriatum neurons prevented slow-to-fast fiber-type transformation in soleus of hindlimb suspended rats.

Functional recordings from awake, behaving rodents through a microchannel based regenerative neural interface

NASA Astrophysics Data System (ADS)

Gore, Russell K.; Choi, Yoonsu; Bellamkonda, Ravi; English, Arthur

2015-02-01

Objective. Neural interface technologies could provide controlling connections between the nervous system and external technologies, such as limb prosthetics. The recording of efferent, motor potentials is a critical requirement for a peripheral neural interface, as these signals represent the user-generated neural output intended to drive external devices. Our objective was to evaluate structural and functional neural regeneration through a microchannel neural interface and to characterize potentials recorded from electrodes placed within the microchannels in awake and behaving animals. Approach. Female rats were implanted with muscle EMG electrodes and, following unilateral sciatic nerve transection, the cut nerve was repaired either across a microchannel neural interface or with end-to-end surgical repair. During a 13 week recovery period, direct muscle responses to nerve stimulation proximal to the transection were monitored weekly. In two rats repaired with the neural interface, four wire electrodes were embedded in the microchannels and recordings were obtained within microchannels during proximal stimulation experiments and treadmill locomotion. Main results. In these proof-of-principle experiments, we found that axons from cut nerves were capable of functional reinnervation of distal muscle targets, whether regenerating through a microchannel device or after direct end-to-end repair. Discrete stimulation-evoked and volitional potentials were recorded within interface microchannels in a small group of awake and behaving animals and their firing patterns correlated directly with intramuscular recordings during locomotion. Of 38 potentials extracted, 19 were identified as motor axons reinnervating tibialis anterior or soleus muscles using spike triggered averaging. Significance. These results are evidence for motor axon regeneration through microchannels and are the first report of in vivo recordings from regenerated motor axons within microchannels in a small group of awake and behaving animals. These unique findings provide preliminary evidence that efferent, volitional motor potentials can be recorded from the microchannel-based peripheral neural interface; a critical requirement for any neural interface intended to facilitate direct neural control of external technologies.

Daily Electrical Muscle Stimulation Enhances Functional Recovery Following Nerve Transection and Repair in Rats.

PubMed

Willand, Michael P; Chiang, Cameron D; Zhang, Jennifer J; Kemp, Stephen W P; Borschel, Gregory H; Gordon, Tessa

2015-08-01

Incomplete recovery following surgical reconstruction of damaged peripheral nerves is common. Electrical muscle stimulation (EMS) to improve functional outcomes has not been effective in previous studies. To evaluate the efficacy of a new, clinically translatable EMS paradigm over a 3-month period following nerve transection and immediate repair. Rats were divided into 6 groups based on treatment (EMS or no treatment) and duration (1, 2, or 3 months). A tibial nerve transection injury was immediately repaired with 2 epineurial sutures. The right gastrocnemius muscle in all rats was implanted with intramuscular electrodes. In the EMS group, the muscle was electrically stimulated with 600 contractions per day, 5 days a week. Terminal measurements were made after 1, 2, or 3 months. Rats in the 3-month group were assessed weekly using skilled and overground locomotion tests. Neuromuscular junction reinnervation patterns were also examined. Muscles that received daily EMS had significantly greater numbers of reinnervated motor units with smaller average motor unit sizes. The majority of muscle endplates were reinnervated by a single axon arising from a nerve trunk with significantly fewer numbers of terminal sprouts in the EMS group, the numbers being small. Muscle mass and force were unchanged but EMS improved behavioral outcomes. Our results demonstrated that EMS using a moderate stimulation paradigm immediately following nerve transection and repair enhances electrophysiological and behavioral recovery. © The Author(s) 2014.

Fiber-type-specific sensitivities and phenotypic adaptations to dietary fat overload differentially impact fast- versus slow-twitch muscle contractile function in C57BL/6J mice.

PubMed

Ciapaite, Jolita; van den Berg, Sjoerd A; Houten, Sander M; Nicolay, Klaas; van Dijk, Ko Willems; Jeneson, Jeroen A

2015-02-01

High-fat diets (HFDs) have been shown to interfere with skeletal muscle energy metabolism and cause peripheral insulin resistance. However, understanding of HFD impact on skeletal muscle primary function, i.e., contractile performance, is limited. Male C57BL/6J mice were fed HFD containing lard (HFL) or palm oil (HFP), or low-fat diet (LFD) for 5weeks. Fast-twitch (FT) extensor digitorum longus (EDL) and slow-twitch (ST) soleus muscles were characterized with respect to contractile function and selected biochemical features. In FT EDL muscle, a 30%-50% increase in fatty acid (FA) content and doubling of long-chain acylcarnitine (C14-C18) content in response to HFL and HFP feeding were accompanied by increase in protein levels of peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial oxidative phosphorylation complexes and acyl-CoA dehydrogenases involved in mitochondrial FA β-oxidation. Peak force of FT EDL twitch and tetanic contractions was unaltered, but the relaxation time (RT) of twitch contractions was 30% slower compared to LFD controls. The latter was caused by accumulation of lipid intermediates rather than changes in the expression levels of proteins involved in calcium handling. In ST soleus muscle, no evidence for lipid overload was found in any HFD group. However, particularly in HFP group, the peak force of twitch and tetanic contractions was reduced, but RT was faster than LFD controls. The latter was associated with a fast-to-slow shift in troponin T isoform expression. Taken together, these data highlight fiber-type-specific sensitivities and phenotypic adaptations to dietary lipid overload that differentially impact fast- versus slow-twitch skeletal muscle contractile function. Copyright © 2015 Elsevier Inc. All rights reserved.

Improvements in exercise performance with high-intensity interval training coincide with an increase in skeletal muscle mitochondrial content and function.

PubMed

Jacobs, Robert Acton; Flück, Daniela; Bonne, Thomas Christian; Bürgi, Simon; Christensen, Peter Møller; Toigo, Marco; Lundby, Carsten

2013-09-01

Six sessions of high-intensity interval training (HIT) are sufficient to improve exercise capacity. The mechanisms explaining such improvements are unclear. Accordingly, the aim of this study was to perform a comprehensive evaluation of physiologically relevant adaptations occurring after six sessions of HIT to determine the mechanisms explaining improvements in exercise performance. Sixteen untrained (43 ± 6 ml·kg(-1)·min(-1)) subjects completed six sessions of repeated (8-12) 60 s intervals of high-intensity cycling (100% peak power output elicited during incremental maximal exercise test) intermixed with 75 s of recovery cycling at a low intensity (30 W) over a 2-wk period. Potential training-induced alterations in skeletal muscle respiratory capacity, mitochondrial content, skeletal muscle oxygenation, cardiac capacity, blood volumes, and peripheral fatigue resistance were all assessed prior to and again following training. Maximal measures of oxygen uptake (Vo2peak; ∼8%; P = 0.026) and cycling time to complete a set amount of work (∼5%; P = 0.008) improved. Skeletal muscle respiratory capacities increased, most likely as a result of an expansion of skeletal muscle mitochondria (∼20%, P = 0.026), as assessed by cytochrome c oxidase activity. Skeletal muscle deoxygenation also increased while maximal cardiac output, total hemoglobin, plasma volume, total blood volume, and relative measures of peripheral fatigue resistance were all unaltered with training. These results suggest that increases in mitochondrial content following six HIT sessions may facilitate improvements in respiratory capacity and oxygen extraction, and ultimately are responsible for the improvements in maximal whole body exercise capacity and endurance performance in previously untrained individuals.

Lack of muscle contractile property changes at the time of perceived physical exhaustion suggests central mechanisms contributing to early motor task failure in patients with cancer-related fatigue.

PubMed

Kisiel-Sajewicz, Katarzyna; Davis, Mellar P; Siemionow, Vlodek; Seyidova-Khoshknabi, Dilara; Wyant, Alexandria; Walsh, Declan; Hou, Juliet; Yue, Guang H

2012-09-01

Fatigue is one of the most common symptoms reported by cancer survivors, and fatigue worsens when patients are engaged in muscle exertion, which results in early motor task failure. Central fatigue plays a significant role, more than muscle (peripheral) fatigue, in contributing to early task failure in cancer-related fatigue (CRF). The purpose of this study was to determine if muscle contractile property alterations (reflecting muscle fatigue) occurred at the end of a low-intensity muscle contraction to exhaustion and if these properties differed between those with CRF and healthy controls. Ten patients (aged 59.9±10.6 years, seven women) with advanced solid cancer and CRF and 12 age- and gender-matched healthy controls (aged 46.6±12.8 years, nine women) performed a sustained contraction of the right arm elbow flexion at 30% maximal level until exhaustion. Peak twitch force, time to peak twitch force, rate of peak twitch force development, and half relaxation time derived from electrical stimulation-evoked twitches were analyzed pre- and post-sustained contraction. CRF patients reported significantly greater fatigue as measured by the Brief Fatigue Inventory and failed the motor task earlier, 340±140 vs. 503±155 seconds in controls. All contractile property parameters did not change significantly in CRF but did change significantly in controls. CRF patients perceive physical exhaustion sooner during a motor fatigue task with minimal muscular fatigue. The observation supports that central fatigue is a more significant factor than peripheral fatigue in causing fatigue feelings and limits motor function in cancer survivors with fatigue symptoms. Copyright © 2012. Published by Elsevier Inc.

Effect of hypercapnia on respiratory and peripheral skeletal muscle loss during critical illness - A pilot study.

PubMed

Twose, Paul; Jones, Una; Wise, Matt P

2018-06-01

Critical illness has profound effects on muscle strength and long-term physical morbidity. However, there remains a paucity of evidence for the aetiology of critical illness related weakness. Recent animal model research identified that hypercapnia may reduce the rate of muscle loss. The aim of this study was to determine the effect of hypercapnia on respiratory and peripheral skeletal muscle in patients with critical illness. A pilot observational study of mechanically ventilated critically ill patients at a tertiary critical care unit who were retrospectively categorised as: 1) Respiratory failure with normocapnia; 2) Respiratory failure with hypercapnia; and 3) brain injury. Diaphragm thickness and quadriceps rectus femoris cross-sectional area (RFCSA) were measured using ultrasound imaging at baseline and at days 3, 5, 7 and 10 of mechanical ventilation. Significant reductions in RFCSA muscle loss were observed for all time-points when compared to baseline [day 10: -14.9%±8.2 p< 0.001], and in diaphragm thickness between baseline and day 7 [day 7: -5.8%±9.5 p=0.029). No correlation was identified between the rate of muscle mass loss in the diaphragm and RFCSA. In this pilot study, peripheral skeletal muscle weakness occurred early and rapidly within the critical care population, irrespective of carbon dioxide levels. Copyright © 2018 Elsevier Inc. All rights reserved.

Mesenchymal Cells of the Intestinal Lamina Propria

PubMed Central

Powell, D.W.; Pinchuk, I.V.; Saada, J.I.; Chen, Xin; Mifflin, R.C.

2013-01-01

The mesenchymal elements of the intestinal lamina propria reviewed here are the myofibroblasts, fibroblasts, mural cells (pericytes) of the vasculature, bone marrow–derived stromal stem cells, smooth muscle of the muscularis mucosae, and smooth muscle surrounding the lymphatic lacteals. These cells share similar marker molecules, origins, and coordinated biological functions previously ascribed solely to subepithelial myofibroblasts. We review the functional anatomy of intestinal mesenchymal cells and describe what is known about their origin in the embryo and their replacement in adults. As part of their putative role in intestinal mucosal morphogenesis, we consider the intestinal stem cell niche. Lastly, we review emerging information about myofibroblasts as nonprofessional immune cells that may be important as an alarm system for the gut and as a participant in peripheral immune tolerance. PMID:21054163

Reduction of a 4q35-encoded nuclear envelope protein in muscle differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ostlund, Cecilia; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Guan, Tinglu

2009-11-13

Muscular dystrophy and peripheral neuropathy have been linked to mutations in genes encoding nuclear envelope proteins; however, the molecular mechanisms underlying these disorders remain unresolved. Nuclear envelope protein p19A is a protein of unknown function encoded by a gene at chromosome 4q35. p19A levels are significantly reduced in human muscle as cells differentiate from myoblasts to myotubes; however, its levels are not similarly reduced in all differentiation systems tested. Because 4q35 has been linked to facioscapulohumeral muscular dystrophy (FSHD) and some adjacent genes are reportedly misregulated in the disorder, levels of p19A were analyzed in muscle samples from patients withmore » FSHD. Although p19A was increased in most cases, an absolute correlation was not observed. Nonetheless, p19A downregulation in normal muscle differentiation suggests that in the cases where its gene is inappropriately re-activated it could affect muscle differentiation and contribute to disease pathology.« less

[Neural control of somatic muscle function in the earthworm, Allobophora longa, and in the leech, Hirudo medicinalis].

PubMed

David, O F

1978-01-01

Studies have been made on the electrical activity of the segmentary nerves and connectives of the abdominal nervous chain in the earthworm and leech. It was shown that the electrical activity of the isolated piece of the abdominal chain of the leech is manifested of periodic outbursts of impulsation. Presumably this central periodicity accounts for the discharge-like pattern of muscle rhythmic activity which was revealed in our earlier investigations. The electrical activity in the central nervous system of the earthworm depends on afferent influences which pass to the ganglia from the peripheral sensory nervous cells. Stimulation of the abdominal nervous chain did not result in extra discharges of muscle activity, but only affected some of the parameters of the latter.

Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis

PubMed Central

Grahn, Peter J.; Mallory, Grant W.; Berry, B. Michael; Hachmann, Jan T.; Lobel, Darlene A.; Lujan, J. Luis

2014-01-01

Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI) can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system's state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles. PMID:25278830

Developmental Programming: Impact of Gestational Steroid and Metabolic Milieus on Mediators of Insulin Sensitivity in Prenatal Testosterone-Treated Female Sheep.

PubMed

Puttabyatappa, Muraly; Andriessen, Victoria; Mesquitta, Makeda; Zeng, Lixia; Pennathur, Subramaniam; Padmanabhan, Vasantha

2017-09-01

Prenatal testosterone (T) excess in sheep leads to peripheral insulin resistance (IR), reduced adipocyte size, and tissue-specific changes, with liver and muscle but not adipose tissue being insulin resistant. To determine the basis for the tissue-specific differences in insulin sensitivity, we assessed changes in negative (inflammation, oxidative stress, and lipotoxicity) and positive mediators (adiponectin and antioxidants) of insulin sensitivity in the liver, muscle, and adipose tissues of control and prenatal T-treated sheep. Because T excess leads to maternal hyperinsulinemia, fetal hyperandrogenism, and functional hyperandrogenism and IR in their female offspring, prenatal and postnatal interventions with antiandrogen, flutamide, and the insulin sensitizer rosiglitazone were used to parse out the contribution of androgenic and metabolic pathways in programming and maintaining these defects. Results showed that (1) peripheral IR in prenatal T-treated female sheep is related to increases in triglycerides and 3-nitrotyrosine, which appear to override the increase in high-molecular-weight adiponectin; (2) liver IR is a function of the increase in oxidative stress (3-nitrotyrosine) and lipotoxicity; (3) muscle IR is related to lipotoxicity; and (4) the insulin-sensitive status of visceral adipose tissue appears to be a function of the increase in antioxidants that likely overrides the increase in proinflammatory cytokines, macrophages, and oxidative stress. Prenatal and postnatal intervention with either antiandrogen or insulin sensitizer had partial effects in preventing or ameliorating the prenatal T-induced changes in mediators of insulin sensitivity, suggesting that both pathways are critical for the programming and maintenance of the prenatal T-induced changes and point to potential involvement of estrogenic pathways. Copyright © 2017 Endocrine Society.

Pulsed radiofrequency of the composite nerve supply to the knee joint as a new technique for relieving osteoarthritic pain: a preliminary report.

PubMed

Vas, Lakshmi; Pai, Renuka; Khandagale, Nishigandha; Pattnaik, Manorama

2014-01-01

We report a new technique for pulsed radiofrequency (PRF) of the entire nerve supply of the knee as an option in treating osteoarthritis (OA) of knee. We targeted both sensory and motor nerves supplying all the structures around the knee: joint, muscles, and skin to address the entire nociception and stiffness leading to peripheral and central sensitization in osteoarthritis. Ten patients with pain, stiffness, and loss of function in both knees were treated with ultrasonography (USG) guided PRF of saphenous, tibial, and common peroneal nerves along with subsartorial, peripatellar, and popliteal plexuses. USG guided PRF of the femoral nerve was also done to address the innervation of the quadriceps muscle. Assessment of pain (Numerical Rating Scale [NRS], pain DETECT, knee function [Western Ontario and McMaster Universities Osteoarthritis Index- WOMAC]) were documented pre and post PRF at 3 and 6 months. Knee radiographs (Kellgren-Lawrence [K-L] grading) were done before PRF and one week later. All the patients showed a sustained improvement of NRS, pain DETECT, and WOMAC at 3 and 6 months. The significant improvement of patellar position and tibio-femoral joint space was concordant with the patient's reporting of improvement in stiffness and pain. The sustained pain relief and muscle relaxation enabled the patients to optimize physiotherapy thereby improving endurance training to include the daily activities of life. We conclude that OA knee pain is a product of neuromyopathy and that PRF of the sensory and motor nerves appeared to be a safe, effective, and minimally invasive technique. The reduction of pain and stiffness improved the knee function and probably reduced the peripheral and central sensitization.

Muscles and their role in episodic tension-type headache: implications for treatment.

PubMed

Bendtsen, L; Ashina, S; Moore, A; Steiner, T J

2016-02-01

Tension-type headache (TTH) imposes a heavy burden on the global population but remains incompletely understood and poorly managed. Here, we review current knowledge of peripheral factors involved in the mechanism of TTH and make recommendations for the treatment of episodic TTH based on these. Peripheral activation or sensitization of myofascial nociceptors is most probably involved in the development of muscle pain and the acute episode of TTH. Repetitive episodes of muscle pain may sensitize the central nervous system resulting in progression of TTH to the chronic form. Thus, muscular factors may be responsible not only for the acute headache episode but also for chronification of the disorder. Simple analgesics and non-steroidal anti-inflammatory drugs are the mainstays of management of individual headache episodes. Ibuprofen 400 mg and aspirin 1000 mg are recommended as drugs of first choice based on treatment effect, safety profile and costs. Non-pharmacological therapies include electromyographic biofeedback, physiotherapy and muscle relaxation therapy. Future studies should aim to identify the triggers of peripheral nociception and how to avoid peripheral and central sensitization. There is a need for more effective, faster acting drugs for acute TTH. Muscular factors play an important role in episodic TTH. Ibuprofen 400 mg and aspirin 1000 mg are recommended as drugs of first choice. © 2015 European Pain Federation - EFIC®

Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging

NASA Astrophysics Data System (ADS)

Tian, Feng; Yang, Wenlong; Mordes, Daniel A.; Wang, Jin-Yuan; Salameh, Johnny S.; Mok, Joanie; Chew, Jeannie; Sharma, Aarti; Leno-Duran, Ester; Suzuki-Uematsu, Satomi; Suzuki, Naoki; Han, Steve S.; Lu, Fa-Ke; Ji, Minbiao; Zhang, Rosanna; Liu, Yue; Strominger, Jack; Shneider, Neil A.; Petrucelli, Leonard; Xie, X. Sunney; Eggan, Kevin

2016-10-01

The study of amyotrophic lateral sclerosis (ALS) and potential interventions would be facilitated if motor axon degeneration could be more readily visualized. Here we demonstrate that stimulated Raman scattering (SRS) microscopy could be used to sensitively monitor peripheral nerve degeneration in ALS mouse models and ALS autopsy materials. Three-dimensional imaging of pre-symptomatic SOD1 mouse models and data processing by a correlation-based algorithm revealed that significant degeneration of peripheral nerves could be detected coincidentally with the earliest detectable signs of muscle denervation and preceded physiologically measurable motor function decline. We also found that peripheral degeneration was an early event in FUS as well as C9ORF72 repeat expansion models of ALS, and that serial imaging allowed long-term observation of disease progression and drug effects in living animals. Our study demonstrates that SRS imaging is a sensitive and quantitative means of measuring disease progression, greatly facilitating future studies of disease mechanisms and candidate therapeutics.

Reduced exercise capacity in untreated adults with primary growth hormone resistance (Laron syndrome).

PubMed

Ben-Dov, Issahar; Gaides, Mark; Scheinowitz, Mickey; Wagner, Rivka; Laron, Zvi

2003-12-01

Primary IGF-I deficiency (Laron syndrome, LS) may decrease exercise capacity as a result of a lack of an IGF-I effect on heart, peripheral muscle or lung structure and/or function. Eight patients (six females) who had never received treatment with IGF-I, with mean age of 36 +/- 10 (SD) years (range 21-48), weight 47 +/- 9 kg (31-61), height 126 +/- 12 cm (112-140) and body mass index of 29 +/- 4 kg/m2 (24-34), and 12 age-matched controls, underwent lung function tests and incremental cycling to the limit of tolerance (CPX, MedGraphics). Predicted values for the patients were derived from adult equations based on height. In LS patients, lung function was near normal; vital capacity was 84 +/- 11% of expected (66-103). Peak exercise O2-uptake and the anaerobic threshold were reduced, 57 +/- 20% of predicted and 33 +/- 9% of predicted peak (P = 0.005 vs. controls), despite normal mean exercise breathing reserve. All parameters were normal in the controls. Exercise capacity in untreated adults with LS is significantly reduced. The limitation for most patients was not ventilatory but resulted either from low cardiac output and/or from dysfunction of the peripheral muscles. However, the relative contribution of each of these elements and/or the role of poor fitness needs further study.

Cushing's syndrome: a model for sarcopenic obesity.

PubMed

Drey, Michael; Berr, Christina M; Reincke, Martin; Fazel, Julia; Seissler, Jochen; Schopohl, Jochen; Bidlingmaier, Martin; Zopp, Stefanie; Reisch, Nicole; Beuschlein, Felix; Osswald, Andrea; Schmidmaier, Ralf

2017-09-01

Obesity and its metabolic impairments are discussed as major risk factors for sarcopenia leading to sarcopenic obesity. Cushing's syndrome is known to be associated with obesity and muscle atrophy. We compared Cushing's syndrome with matched obese controls regarding body composition, physical performance, and biochemical markers to test the hypothesis that Cushing's syndrome could be a model for sarcopenic obesity. By propensity score matching, 47 controls were selected by body mass index and gender as obese controls. Fat mass and muscle mass were measured by bioelectrical impedance analysis. Muscle function was assessed by chair rising test and hand grip strength. Biochemical markers of glucose and lipid metabolism and inflammation (hsCRP) were measured in peripheral blood. Muscle mass did not differ between Cushing's syndrome and obese controls. However, Cushing's syndrome patients showed significantly greater chair rising time (9.5 s vs. 7.3 s, p = 0.008) and significantly lower hand grip strength (32.1 kg vs. 36.8 kg, p = 0.003). Cushing's syndrome patients with impaired fasting glucose have shown the highest limitations in hand grip strength and chair rising time. Similar to published data in ageing medicine, Cushing's syndrome patients show loss of muscle function that cannot be explained by loss of muscle mass. Impaired muscle quality due to fat infiltration may be the reason. This is supported by the observation that Cushing's syndrome patients with impaired glucose metabolism show strongest deterioration of muscle function. Research in sarcopenic obesity in elderly is hampered by confounding comorbidities and polypharmacy. As Cushing's syndrome patients are frequently free of comorbidities and as Cushing's syndrome is potentially curable we suggest Cushing's syndrome as a clinical model for further research in sarcopenic obesity.

A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8.

PubMed

Bouhy, Delphine; Juneja, Manisha; Katona, Istvan; Holmgren, Anne; Asselbergh, Bob; De Winter, Vicky; Hochepied, Tino; Goossens, Steven; Haigh, Jody J; Libert, Claude; Ceuterick-de Groote, Chantal; Irobi, Joy; Weis, Joachim; Timmerman, Vincent

2018-01-01

Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot-Marie-Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been shown to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. To test this hypothesis and better dissect the pathomechanism of mutant HSPB8, we generated a new transgenic mouse model leading to the expression of the mutant protein (knock-in lines) or the loss-of-function (functional knock-out lines) of the endogenous protein Hspb8. While the homozygous knock-in mice developed motor deficits associated with degeneration of peripheral nerves and severe muscle atrophy corroborating patient data, homozygous knock-out mice had locomotor performances equivalent to those of wild-type animals. The distal skeletal muscles of the post-symptomatic homozygous knock-in displayed Z-disk disorganisation, granulofilamentous material accumulation along with Hspb8, αB-crystallin (HSPB5/CRYAB), and desmin aggregates. The presence of the aggregates correlated with reduced markers of effective autophagy. The sciatic nerve of the homozygous knock-in mice was characterized by low autophagy potential in pre-symptomatic and Hspb8 aggregates in post-symptomatic animals. On the other hand, the sciatic nerve of the homozygous knock-out mice presented a normal morphology and their distal muscle displayed accumulation of abnormal mitochondria but intact myofiber and Z-line organisation. Our data, therefore, suggest that toxic gain-of-function of mutant Hspb8 aggregates is a major contributor to the peripheral neuropathy and the myopathy. In addition, mutant Hspb8 induces impairments in autophagy that may aggravate the phenotype.

[Endurance training and cardial adaptation (athlete's heart)].

PubMed

Dickhuth, Hans-Hermann; Röcker, Kai; Mayer, Frank; König, Daniel; Korsten-Reck, Ulrike

2004-06-01

One essential function of the cardiovascular system is to provide an adequate blood supply to all organs, including the skeletal muscles at rest and during exercise. Adaptation to chronic exercise proceeds mainly via the autonomic nervous system. On the one hand, peripheral muscles influence the autonomic reactions through "feedback" control via ergoreceptors, in particular, mechano- and chemoreceptors. On the other hand, there is central control in the sense of a "feed forward" regulation, e. g., the reaction of an athlete before competition. Along with other influential factors, such as circulatory presso-, chemo-, and volume receptors, the incoming impulses are processed in vegetative centers.A cardiovascular reaction, then, is the result of nerval and humoral sympathetic and parasympathetic activity. At rest, the parasympathetic tone dominates. It reduces heart frequency and conduction velocity. The high vagal tone is initially reduced with increasing physical exertion and switches at higher intensity to increasingly sympathetic activation. This mechanism of reaction to exercise is supported by inverse central and peripheral transmissions.Chronic endurance training leads to an improved local aerobic capacity of the exercised musculature. At rest, it augments parasympathetic activity when the muscle mass is sufficiently large, i. e., 20-30% of the skeletal musculature. The extent of the adaptation depends on individual factors, such as scope, intensity of training, and type of muscle fiber. A higher vagal tone delays the increase in the sympathetic tone during physical exertion. The regulatory range of heart rate, contractility, diastolic function, and blood pressure is increased. In addition, adaptation results in functional and structural changes in the vascular system. Cardiocirculatory work is economized, and maximum performance and oxygen uptake are improved. Endurance training exceeding an individual limit causes harmonic enlargement and hypertrophy of the heart. The thickness of both, the septum and posterior wall increases to the same extent as the interior volume. The mass/volume ratio, and therefore the maximum systolic wall stress, remains constant in contrast to pathologic forms of hypertrophy. Adaptations, including function and size of the heart, show a regression in healthy inactive persons without any structural heart disease.

Deficiency of merosin in dystrophic dy mouse homologue of congenital muscular dystrophy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunada, Y.; Campbell, K.P.; Bernier, S.M.

1994-09-01

Merosin (laminin M chain) is the predominant laminin isoform in the basal lamina of striated muscle and peripheral nerve and is a native ligand for {alpha}-dystroglycan, a novel laminin receptor. Merosin is linked to the subsarcolemmal actin cytoskeleton via the dystrophin-glycoprotein complex (DGC), which plays an important role for maintenance of normal muscle function. We have mapped the mouse merosin gene, Lamm, to the region containing the dystrophia muscularis (dy) locus on chromosome 10. This suggested the possibility that a mutation in the merosin gene could be responsible for the dy mouse, an animal model for autosomal recessive muscular dystrophy,more » and prompted us to test this hypothesis. We analyzed the status of merosin expression in dy mouse by immunofluorescence and immunoblotting. In dy mouse skeletal and cardiac muscle and peripheral nerve, merosin was reduced greater than 90% as compared to control mice. However, the expression of laminin B1/B2 chains and collagen type IV was smaller to that in control mice. These findings strongly suggest that merosin deficiency may be the primary defect in the dy mouse. Furthermore, we have identified two patients afflicted with congenital muscular dystrophy with merosin deficiency, providing the basis for future studies of molecular pathogenesis and gene therapy.« less

The two main theories on dental bruxism.

PubMed

Behr, Michael; Hahnel, Sebastian; Faltermeier, Andreas; Bürgers, Ralf; Kolbeck, Carola; Handel, Gerhard; Proff, Peter

2012-03-20

Bruxism is characterized by non-functional contact of mandibular and maxillary teeth resulting in clenching or grating of teeth. Theories on factors causing bruxism are a matter of controversy in current literature. The dental profession has predominantly viewed peripheral local morphological disorders, such as malocclusion, as the cause of clenching and gnashing. This etiological model is based on the theory that occlusal maladjustment results in reduced masticatory muscle tone. In the absence of occlusal equilibration, motor neuron activity of masticatory muscles is triggered by periodontal receptors. The second theory assumes that central disturbances in the area of the basal ganglia are the main cause of bruxism. An imbalance in the circuit processing of the basal ganglia is supposed to be responsible for muscle hyperactivity during nocturnal dyskinesia such as bruxism. Some authors assume that bruxism constitutes sleep-related parafunctional activity (parasomnia). A recent model, which may explain the potential imbalance of the basal ganglia, is neuroplasticity. Neural plasticity is based on the ability of synapses to change the way they work. Activation of neural plasticity can change the relationship between inhibitory and excitatory neurons. It seems obvious that bruxism is not a symptom specific to just one disease. Many forms (and causes) of bruxism may exist simultaneously, as, for example, peripheral or central forms. Copyright © 2011 Elsevier GmbH. All rights reserved.

Permanent reorganization of Ia afferent synapses on motoneurons after peripheral nerve injuries

PubMed Central

Alvarez, Francisco J.; Bullinger, Katie L.; Titus, Haley E.; Nardelli, Paul; Cope, Timothy C.

2010-01-01

After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons. PMID:20536938

Skeletal Muscle as a Peripheral Modifier of Behavior

ERIC Educational Resources Information Center

Jenkins, Robert R.

1978-01-01

Discusses how muscle can exert an influence on the behavioral potential of an organism and attempts to refute the "all or none law" by demonstrating that skeletal muscle is not merely a slave of the central nervous system. (Author/MA)

Exercise physiology in heart failure and preserved ejection fraction.

PubMed

Haykowsky, Mark J; Kitzman, Dalane W

2014-07-01

Recent advances in the pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFPEF) suggest that noncardiac peripheral factors contribute to the reduced peak V(o2) (peak exercise oxygen uptake) and to its improvement after endurance exercise training. A greater understanding of the peripheral skeletal muscle vascular adaptations that occur with physical conditioning may allow for tailored exercise rehabilitation programs. The identification of specific mechanisms that improve whole body and peripheral skeletal muscle oxygen uptake could establish potential therapeutic targets for medical therapies and a means to follow therapeutic response. Copyright © 2014 Elsevier Inc. All rights reserved.

Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

PubMed

Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

2012-04-01

Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.

38 CFR 4.55 - Principles of combined ratings for muscle injuries.

Code of Federal Regulations, 2014 CFR

2014-07-01

... ratings for muscle injuries. 4.55 Section 4.55 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Principles of combined ratings for muscle injuries. (a) A muscle injury rating will not be combined with a peripheral nerve paralysis rating of the same body part, unless the injuries affect entirely different...

38 CFR 4.55 - Principles of combined ratings for muscle injuries.

Code of Federal Regulations, 2013 CFR

2013-07-01

... ratings for muscle injuries. 4.55 Section 4.55 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Principles of combined ratings for muscle injuries. (a) A muscle injury rating will not be combined with a peripheral nerve paralysis rating of the same body part, unless the injuries affect entirely different...

38 CFR 4.55 - Principles of combined ratings for muscle injuries.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ratings for muscle injuries. 4.55 Section 4.55 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Principles of combined ratings for muscle injuries. (a) A muscle injury rating will not be combined with a peripheral nerve paralysis rating of the same body part, unless the injuries affect entirely different...

38 CFR 4.55 - Principles of combined ratings for muscle injuries.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ratings for muscle injuries. 4.55 Section 4.55 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Principles of combined ratings for muscle injuries. (a) A muscle injury rating will not be combined with a peripheral nerve paralysis rating of the same body part, unless the injuries affect entirely different...

38 CFR 4.55 - Principles of combined ratings for muscle injuries.

Code of Federal Regulations, 2012 CFR

2012-07-01

... ratings for muscle injuries. 4.55 Section 4.55 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Principles of combined ratings for muscle injuries. (a) A muscle injury rating will not be combined with a peripheral nerve paralysis rating of the same body part, unless the injuries affect entirely different...

Neuromuscular dysfunction in type 2 diabetes: underlying mechanisms and effect of resistance training.

PubMed

Orlando, Giorgio; Balducci, Stefano; Bazzucchi, Ilenia; Pugliese, Giuseppe; Sacchetti, Massimo

2016-01-01

Diabetic patients are at higher risk of developing physical disabilities than non-diabetic subjects. Physical disability appears to be related, at least in part, to muscle dysfunction. Several studies have reported reduced muscle strength and power under dynamic and static conditions in both the upper and lower limbs of patients with type 2 diabetes. Additional effects of diabetes include a reduction in muscle mass, quality, endurance and an alteration in muscle fibre composition, though the available data on these parameters are conflicting. The impact of diabetes on neuromuscular function has been related to the co-existence of long-term complications. Peripheral neuropathy has been shown to affect muscle by impairing motor nerve conduction. Also, vascular complications may contribute to the decline in muscle strength. However, muscle dysfunction occurs early in the course of diabetes and affects also the upper limbs, thus suggesting that it may develop independently of micro and macrovascular disease. A growing body of evidence indicates that hyperglycaemia may cause an alteration of the intrinsic properties of the muscle to generate force, via several mechanisms. Recently, resistance exercise has been shown to be an effective strategy to counteract the deterioration of muscular performance. High-intensity exercise seems to provide greater benefits than moderate-intensity training, whereas the effect of a power training is yet unknown. This article reviews the available literature on the impairment of muscle function induced by diabetes, the underlying mechanisms, and the effect of resistance training on this defect. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

"Long-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves".

PubMed

Christie, Breanne P; Freeberg, Max; Memberg, William D; Pinault, Gilles J C; Hoyen, Harry A; Tyler, Dustin J; Triolo, Ronald J

2017-07-11

Electrical stimulation of the peripheral nerves has been shown to be effective in restoring sensory and motor functions in the lower and upper extremities. This neural stimulation can be applied via non-penetrating spiral nerve cuff electrodes, though minimal information has been published regarding their long-term performance for multiple years after implantation. Since 2005, 14 human volunteers with cervical or thoracic spinal cord injuries, or upper limb amputation, were chronically implanted with a total of 50 spiral nerve cuff electrodes on 10 different nerves (mean time post-implant 6.7 ± 3.1 years). The primary outcome measures utilized in this study were muscle recruitment curves, charge thresholds, and percent overlap of recruited motor unit populations. In the eight recipients still actively involved in research studies, 44/45 of the spiral contacts were still functional. In four participants regularly studied over the course of 1 month to 10.4 years, the charge thresholds of the majority of individual contacts remained stable over time. The four participants with spiral cuffs on their femoral nerves were all able to generate sufficient moment to keep the knees locked during standing after 2-4.5 years. The dorsiflexion moment produced by all four fibular nerve cuffs in the active participants exceeded the value required to prevent foot drop, but no tibial nerve cuffs were able to meet the plantarflexion moment that occurs during push-off at a normal walking speed. The selectivity of two multi-contact spiral cuffs was examined and both were still highly selective for different motor unit populations for up to 6.3 years after implantation. The spiral nerve cuffs examined remain functional in motor and sensory neuroprostheses for 2-11 years after implantation. They exhibit stable charge thresholds, clinically relevant recruitment properties, and functional muscle selectivity. Non-penetrating spiral nerve cuff electrodes appear to be a suitable option for long-term clinical use on human peripheral nerves in implanted neuroprostheses.

Neural Mechanisms Underlying Lower Urinary Tract Dysfunction

PubMed Central

Ogawa, Teruyuki; Miyazato, Minoru; Kitta, Takeya; Furuta, Akira; Chancellor, Michael B.; Tyagi, Pradeep

2014-01-01

This article summarizes anatomical, neurophysiological, and pharmacological studies in humans and animals to provide insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract and alterations in these mechanisms in lower urinary tract dysfunction. The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Therefore, injury or diseases of the nervous system, as well as disorders of the peripheral organs, can produce lower urinary tract dysfunction, leading to lower urinary tract symptoms, including both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying pathological changes in lower urinary tract function is discussed. PMID:24578802

Profile of patients with chronic obstructive pulmonary disease classified as physically active and inactive according to different thresholds of physical activity in daily life

PubMed Central

Furlanetto, Karina C.; Pinto, Isabela F. S.; Sant’Anna, Thais; Hernandes, Nidia A.; Pitta, Fabio

2016-01-01

ABSTRACT Objective To compare the profiles of patients with chronic obstructive pulmonary disease (COPD) considered physically active or inactive according to different classifications of the level of physical activity in daily life (PADL). Method Pulmonary function, dyspnea, functional status, body composition, exercise capacity, respiratory and peripheral muscle strength, and presence of comorbidities were assessed in 104 patients with COPD. The level of PADL was quantified with a SenseWear Armband activity monitor. Three classifications were used to classify the patients as physically active or inactive: 30 minutes of activity/day with intensity >3.2 METs, if age ≥65 years, and >4 METs, if age <65 years; 30 minutes of activity/day with intensity >3.0 METs, regardless of patient age; and 80 minutes of activity/day with intensity >3.0 METs, regardless of patient age. Results In all classifications, when compared with the inactive group, the physically active group had better values of anthropometric variables (higher fat-free mass, lower body weight, body mass index and fat percentage), exercise capacity (6-minute walking distance), lung function (forced vital capacity) and functional status (personal care domain of the London Chest Activity of Daily Living). Furthermore, patients classified as physically active in two classifications also had better peripheral and expiratory muscle strength, airflow obstruction, functional status, and quality of life, as well as lower prevalence of heart disease and mortality risk. Conclusion In all classification methods, physically active patients with COPD have better exercise capacity, lung function, body composition, and functional status compared to physically inactive patients. PMID:27683835

Peripheral Serotonin: a New Player in Systemic Energy Homeostasis

PubMed Central

Namkung, Jun; Kim, Hail; Park, Sangkyu

2015-01-01

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment. PMID:26628041

[Professor DONG Gui-rong's experience for the treatment of peripheral facial paralysis].

PubMed

Cao, Lian-Ying; Shen, Te-Li; Zhang, Wei; Chen, Si-Hui

2012-05-01

Professor DONG Gui-rong's theoretical principle and manipulation points for peripheral facial paralysis were introduced in details from the angels of syndrome differentiation, timing, acupoint prescription and needling methods. For the syndrome differentiation and timing, the professor emphasized to check the treatment timing and follow the symptoms, which should be treated by stages, besides, it was necessary to find and distinguish the reason and nature of diseases to have a combined treatment of tendons and muscles. For the acupoint prescription and needling methods, he has proposed that the acupoints selection should be compatible of distal and lacal, and made a best of Baihui (GV 20) to regulate the whole yang qi, also he has paid much attention to the needling methods and staging treatment. Under the consideration of late stage of peripheral facial paralysis, based on syndrome differentiation Back-shu points have been selected to regulate zang-fu function, should achieve much better therapeutic effect.

Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease

PubMed Central

Fuld, J; Kilduff, L; Neder, J; Pitsiladis, Y; Lean, M; Ward, S; Cotton, M

2005-01-01

Background: Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease (COPD). Creatine nutritional supplementation produces increased muscle mass and exercise performance in health. A controlled study was performed to look for similar effects in 38 patients with COPD. Methods: Thirty eight patients with COPD (mean (SD) forced expiratory volume in 1 second (FEV1) 46 (15)% predicted) were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2 weeks loading (one dose three times daily), patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance (once daily) supplementation. Pulmonary function, body composition, and exercise performance (peripheral muscle strength and endurance, shuttle walking, cycle ergometry) took place at baseline (n = 38), post loading (n = 36), and post rehabilitation (n = 25). Results: No difference was found in whole body exercise performance between the groups: for example, incremental shuttle walk distance mean –23.1 m (95% CI –71.7 to 25.5) post loading and –21.5 m (95% CI –90.6 to 47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI 0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation. Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI 1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI 131.3 to 1577.4) post rehabilitation. Creatine improved health status between baseline and post rehabilitation (St George's Respiratory Questionnaire total score –7.7 (95% CI –14.9 to –0.5)). Conclusions: Creatine supplementation led to increases in fat-free mass, peripheral muscle strength and endurance, health status, but not exercise capacity. Creatine may constitute a new ergogenic treatment in COPD. PMID:15994258

Altered Achilles tendon function during walking in people with diabetic neuropathy: implications for metabolic energy saving.

PubMed

Petrovic, M; Maganaris, C N; Deschamps, K; Verschueren, S M; Bowling, F L; Boulton, A J M; Reeves, N D

2018-05-01

The Achilles tendon (AT) has the capacity to store and release elastic energy during walking, contributing to metabolic energy savings. In diabetes patients, it is hypothesized that a stiffer Achilles tendon may reduce the capacity for energy saving through this mechanism, thereby contributing to an increased metabolic cost of walking (CoW). The aim of this study was to investigate the effects of diabetes and diabetic peripheral neuropathy (DPN) on the Achilles tendon and plantarflexor muscle-tendon unit behavior during walking. Twenty-three nondiabetic controls (Ctrl); 20 diabetic patients without peripheral neuropathy (DM), and 13 patients with moderate/severe DPN underwent gait analysis using a motion analysis system, force plates, and ultrasound measurements of the gastrocnemius muscle, using a muscle model to determine Achilles tendon and muscle-tendon length changes. During walking, the DM and particularly the DPN group displayed significantly less Achilles tendon elongation (Ctrl: 1.81; DM: 1.66; and DPN: 1.54 cm), higher tendon stiffness (Ctrl: 210; DM: 231; and DPN: 240 N/mm), and higher tendon hysteresis (Ctrl: 18; DM: 21; and DPN: 24%) compared with controls. The muscle fascicles of the gastrocnemius underwent very small length changes in all groups during walking (~0.43 cm), with the smallest length changes in the DPN group. Achilles tendon forces were significantly lower in the diabetes groups compared with controls (Ctrl: 2666; DM: 2609; and DPN: 2150 N). The results strongly point toward the reduced energy saving capacity of the Achilles tendon during walking in diabetes patients as an important factor contributing to the increased metabolic CoW in these patients. NEW & NOTEWORTHY From measurements taken during walking we observed that the Achilles tendon in people with diabetes and particularly people with diabetic peripheral neuropathy was stiffer, was less elongated, and was subject to lower forces compared with controls without diabetes. These altered properties of the Achilles tendon in people with diabetes reduce the tendon's energy saving capacity and contribute toward the higher metabolic energy cost of walking in these patients.

Whole limb kinematics are preferentially conserved over individual joint kinematics after peripheral nerve injury

PubMed Central

Chang, Young-Hui; Auyang, Arick G.; Scholz, John P.; Nichols, T. Richard

2009-01-01

Summary Biomechanics and neurophysiology studies suggest whole limb function to be an important locomotor control parameter. Inverted pendulum and mass-spring models greatly reduce the complexity of the legs and predict the dynamics of locomotion, but do not address how numerous limb elements are coordinated to achieve such simple behavior. As a first step, we hypothesized whole limb kinematics were of primary importance and would be preferentially conserved over individual joint kinematics after neuromuscular injury. We used a well-established peripheral nerve injury model of cat ankle extensor muscles to generate two experimental injury groups with a predictable time course of temporary paralysis followed by complete muscle self-reinnervation. Mean trajectories of individual joint kinematics were altered as a result of deficits after injury. By contrast, mean trajectories of limb orientation and limb length remained largely invariant across all animals, even with paralyzed ankle extensor muscles, suggesting changes in mean joint angles were coordinated as part of a long-term compensation strategy to minimize change in whole limb kinematics. Furthermore, at each measurement stage (pre-injury, paralytic and self-reinnervated) step-by-step variance of individual joint kinematics was always significantly greater than that of limb orientation. Our results suggest joint angle combinations are coordinated and selected to stabilize whole limb kinematics against short-term natural step-by-step deviations as well as long-term, pathological deviations created by injury. This may represent a fundamental compensation principle allowing animals to adapt to changing conditions with minimal effect on overall locomotor function. PMID:19837893

Cardiovascular Responses to Skeletal Muscle Stretching: "Stretching" the Truth or a New Exercise Paradigm for Cardiovascular Medicine?

PubMed

Kruse, Nicholas T; Scheuermann, Barry W

2017-12-01

Stretching is commonly prescribed with the intended purpose of increasing range of motion, enhancing muscular coordination, and preventing prolonged immobilization induced by aging or a sedentary lifestyle. Emerging evidence suggests that acute or long-term stretching exercise may modulate a variety of cardiovascular responses. Specifically, at the onset of stretch, the mechanical deformation of the vascular bed coupled with stimulation of group III muscle afferent fibers initiates a cascade of events resulting in both peripheral vasodilation and a heart rate-driven increase in cardiac output, blood pressure, and muscle blood flow. This potential to increase shear stress and blood flow without the use of excessive muscle energy expenditure may hold important implications for future therapeutic vascular medicine and cardiac health. However, the idea that a cardiovascular component may be involved in human skeletal muscle stretching is relatively new. Therefore, the primary intent of this review is to highlight topics related to skeletal muscle stretching and cardiovascular regulation and function. The current evidence suggests that acute stretching causes a significant macro- and microcirculatory event that alters blood flow and the relationship between oxygen availability and oxygen utilization. These acute vascular changes if performed chronically may result in improved endothelial function, improved arterial blood vessel stiffness, and/or reduced blood pressure. Although several mechanisms have been postulated, an increased nitric oxide bioavailability has been highlighted as one promising candidate for the improvement in vessel function with stretching. Collectively, the evidence provided in this review suggests that stretching acutely or long term may serve as a novel and alternative low intensity therapeutic intervention capable of improving several parameters of vascular function.

Nerve transfers in tetraplegia I: Background and technique

PubMed Central

Brown, Justin M.

2011-01-01

Background: The recovery of hand function is consistently rated as the highest priority for persons with tetraplegia. Recovering even partial arm and hand function can have an enormous impact on independence and quality of life of an individual. Currently, tendon transfers are the accepted modality for improving hand function. In this procedure, the distal end of a functional muscle is cut and reattached at the insertion site of a nonfunctional muscle. The tendon transfer sacrifices the function at a lesser location to provide function at a more important location. Nerve transfers are conceptually similar to tendon transfers and involve cutting and connecting a healthy but less critical nerve to a more important but paralyzed nerve to restore its function. Methods: We present a case of a 28-year-old patient with a C5-level ASIA B (international classification level 1) injury who underwent nerve transfers to restore arm and hand function. Intact peripheral innervation was confirmed in the paralyzed muscle groups corresponding to finger flexors and extensors, wrist flexors and extensors, and triceps bilaterally. Volitional control and good strength were present in the biceps and brachialis muscles, the deltoid, and the trapezius. The patient underwent nerve transfers to restore finger flexion and extension, wrist flexion and extension, and elbow extension. Intraoperative motor-evoked potentials and direct nerve stimulation were used to identify donor and recipient nerve branches. Results: The patient tolerated the procedure well, with a preserved function in both elbow flexion and shoulder abduction. Conclusions: Nerve transfers are a technically feasible means of restoring the upper extremity function in tetraplegia in cases that may not be amenable to tendon transfers. PMID:21918736

Microneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans.

PubMed

Mano, Tadaaki; Iwase, Satoshi; Toma, Shinobu

2006-11-01

Microneurography is a method using metal microelectrodes to investigate directly identified neural traffic in myelinated as well as unmyelinated efferent and afferent nerves leading to and coming from muscle and skin in human peripheral nerves in situ. The present paper reviews how this technique has been used in clinical neurophysiology to elucidate the neural mechanisms of autonomic regulation, motor control and sensory functions in humans under physiological and pathological conditions. Microneurography is particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers. The recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin (muscle sympathetic nerve activity; MSNA and skin sympathetic nerve activity; SSNA) provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands. Sympathetic microneurography has become a potent tool to reveal neural functions and dysfunctions concerning blood pressure control and thermoregulation. This recording has been used not only in wake conditions but also in sleep to investigate changes in sympathetic neural traffic during sleep and sleep-related events such as sleep apnea. The same recording was also successfully carried out by astronauts during spaceflight. Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control. Muscle spindle afferent information is particularly important for the control of fine precise movements. It may also play important roles to predict behavior outcomes during learning of a motor task. Recordings of discharges in myelinated afferent fibers from skin mechanoreceptors have provided not only objective information about mechanoreceptive cutaneous sensation but also the roles of these signals in fine motor control. Unmyelinated mechanoreceptive afferent discharges from hairy skin seem to be important to convey cutaneous sensation to the central structures related to emotion. Recordings of afferent discharges in thin myelinated and unmyelinated fibers from nociceptors in muscle and skin have been used to provide information concerning pain. Recordings of afferent discharges of different types of cutaneous C-nociceptors identified by marking method have become an important tool to reveal the neural mechanisms of cutaneous sensations such as an itch. No direct microneurographic evidence has been so far proved regarding the effects of sympathoexcitation on sensitization of muscle and skin sensory receptors at least in healthy humans.

Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury.

PubMed

Birenbaum, Nathan K; MacEwan, Matthew R; Ray, Wilson Z

2017-06-01

Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T 9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.

The diving paradox: new insights into the role of the dive response in air-breathing vertebrates.

PubMed

Davis, Randall W; Polasek, Lori; Watson, Rebecca; Fuson, Amanda; Williams, Terrie M; Kanatous, Shane B

2004-07-01

When aquatic reptiles, birds and mammals submerge, they typically exhibit a dive response in which breathing ceases, heart rate slows, and blood flow to peripheral tissues is reduced. The profound dive response that occurs during forced submergence sequesters blood oxygen for the brain and heart while allowing peripheral tissues to become anaerobic, thus protecting the animal from immediate asphyxiation. However, the decrease in peripheral blood flow is in direct conflict with the exercise response necessary for supporting muscle metabolism during submerged swimming. In free diving animals, a dive response still occurs, but it is less intense than during forced submergence, and whole-body metabolism remains aerobic. If blood oxygen is not sequestered for brain and heart metabolism during normal diving, then what is the purpose of the dive response? Here, we show that its primary role may be to regulate the degree of hypoxia in skeletal muscle so that blood and muscle oxygen stores can be efficiently used. Paradoxically, the muscles of diving vertebrates must become hypoxic to maximize aerobic dive duration. At the same time, morphological and enzymatic adaptations enhance intracellular oxygen diffusion at low partial pressures of oxygen. Optimizing the use of blood and muscle oxygen stores allows aquatic, air-breathing vertebrates to exercise for prolonged periods while holding their breath.

Disparate Changes in Plasma and Brainstem Cytokine Levels in Adult and Ageing Rats Associated with Age-Related Changes in Facial Motor Neuron Number, Snout Muscle Morphology, and Exploratory Behavior.

PubMed

Katharesan, Viythia; Lewis, Martin David; Vink, Robert; Johnson, Ian Paul

2016-01-01

An overall increase in inflammatory cytokines with age in both the blood and the central nervous system (CNS) has been proposed to explain many aspects of ageing, including decreased motor function and neurodegeneration. This study tests the hypothesis that age-related increases in inflammatory cytokines in the blood and CNS lead to facial motor neuron degeneration. Groups of 3-5 female Sprague-Dawley rats aged 3, 12-18, and 24 months were used. Twelve cytokines interleukin (IL)-1α, IL-β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNFα), interferon-γ, and granulocyte macrophage-colony stimulating factor were measured in blood plasma and compared with those in the brainstem after first flushing blood from its vessels. The open-field test was used to measure exploratory behavior, and the morphology of the peripheral target muscle of facial motor neurons quantified. Total numbers of facial motor neurons were determined stereologically in separate groups of 3- and 24-month-old rats. Ageing rats showed a significant 30-42% decrease in blood plasma (peripheral) concentrations of IL-12p70 and TNFα and a significant 43-49% increase in brainstem (central) concentrations of IL-1α, IL-2, IL-4, IL-10, and TNFα. They also showed significant reductions in motor neuron number in the right but not left facial nucleus, reduced exploratory behavior, and increase in peripheral target muscle size. Marginal age-related facial motoneuronal loss occurs in the ageing rat and is characterized by complex changes in the inflammatory signature, rather than a general increase in inflammatory cytokines.

Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury.

PubMed

Lin, Tao; Qiu, Shuai; Yan, Liwei; Zhu, Shuang; Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin

2018-05-01

Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018. © 2017 Wiley Periodicals, Inc.

Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibers and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609.

PubMed

Grunnet, Louise G; Brøns, Charlotte; Jacobsen, Stine; Nilsson, Emma; Astrup, Arne; Hansen, Torben; Pedersen, Oluf; Poulsen, Pernille; Quistorff, Bjørn; Vaag, Allan

2009-02-01

Recent studies identified the rs9939609 A-allele of the FTO (fat mass and obesity associated) gene as being associated with obesity and type 2 diabetes. We studied the role of the A-allele in the regulation of peripheral organ functions involved in the pathogenesis of obesity and type 2 diabetes. Forty-six young men underwent a hyperinsulinemic euglycemic clamp with excision of skeletal muscle biopsies, an iv glucose tolerance test, 31phosphorous magnetic resonance spectroscopy, and 24-h whole body metabolism was measured in a respiratory chamber. The FTO rs9939609 A-allele was associated with elevated fasting blood glucose and plasma insulin, hepatic insulin resistance, and shorter recovery half-times of phosphocreatine and inorganic phosphate after exercise in a primarily type I muscle. These relationships--except for fasting insulin--remained significant after correction for body fat percentage. The risk allele was not associated with fat distribution, peripheral insulin sensitivity, insulin secretion, 24-h energy expenditure, or glucose and fat oxidation. The FTO genotype did not influence the mRNA expression of FTO or a set of key nuclear or mitochondrially encoded genes in skeletal muscle during rest. Increased energy efficiency--and potentially increased mitochondrial coupling--as suggested by faster recovery rates of phosphocreatine and inorganic phosphate in oxidative muscle fibers may contribute to the increased risk of obesity and type 2 diabetes in homozygous carriers of the FTO A-risk allele. Hepatic insulin resistance may represent the key metabolic defect responsible for mild elevations of fasting blood glucose associated with the FTO phenotype.

Whole-body vibration training improves balance, muscle strength and glycosylated hemoglobin in elderly patients with diabetic neuropathy.

PubMed

Lee, Kyoungjin; Lee, Seungwon; Song, Changho

2013-12-01

Elderly patients with diabetes and peripheral neuropathy are more likely to experience falls. However, the information available on how such falls can be prevented is scarce. We investigated the effects of whole-body vibration (WBV) combined with a balance exercise program on balance, muscle strength, and glycosylated hemoglobin (HbA1c) in elderly patients with diabetic peripheral neuropathy. Fifty-five elderly patients with diabetic neuropathy were randomly assigned to WBV with balance exercise group, balance exercise (BE) group, and control group. The WBV and BE groups performed the balance exercise program for 60 min per day, 2 times per week, for 6 weeks. Further, the WBV group performed WBV training (up to 3 × 3 min, 3 times per week, for 6 weeks). The control group did not participate in any training. The main outcome measures were assessed at baseline and after 6 weeks of training; namely, we assessed the postural sway and one leg stance (OLS) for static balance; Berg balance scale (BBS), timed up-and-go (TUG) test, and functional reach test (FRT) for dynamic balance; five-times-sit-to-stand (FTSTS) test for muscle strength; and HbA1c for predicting the progression of diabetes. Significant improvements were noted in the static balance, dynamic balance, muscle strength, and HbA1c in the WBV group, compared to the BE and control groups (P < 0.05). Thus, in combination with the balance exercise program, the short-term WBV therapy is beneficial in improving balance, muscle strength and HbA1c, in elderly patients with diabetic neuropathy who are at high risk for suffering falls.

Sericin and swimming on histomorphometric parameters of denervated plantar muscle in Wistar rats.

PubMed

Santana, André Junior; Debastiani, Jean Carlos; Buratti, Pâmela; Peretti, Ana Luiza; Kunz, Regina Inês; Brancalhão, Rose Meire Costa; Ribeiro, Lucinéia de Fátima Chasko; Torrejais, Márcia Miranda; Bertolini, Gladson Ricardo Flor

2018-01-01

Objective To analyze the combined effects of the silk protein sericin and swimming exercise on histomorphometry of the plantar muscle in Wistar rats. Methods Forty adult rats were randomly allocated into 5 groups comprising 8 animals each, as follows: Control, Injury, Sericin, Swim, and Swim plus Sericin. Three days after crushing of the sciatic nerve the rats in the Swim and Swim plus Sericin Groups were submitted to swimming exercise for 21 days. Rats were then euthanized and the plantar muscle harvested and processed. Results Cross-sectional area, peripheral nuclei and muscle fiber counts, nucleus/fiber ratio and smallest muscle fiber width did not differ significantly between groups. Morphological analysis revealed hypertrophic fibers in the Swim Group and evident muscle damage in the Swim plus Sericin and Injury Groups. The percentage of intramuscular collagen was apparently maintained in the Swim Group compared to remaining groups. Conclusion Combined treatment with sericin and swimming exercise did not improve muscle properties. However, physical exercise alone was effective in maintaining intramuscular connective tissue and preventing progression of deleterious effects of peripheral nerve injury.

Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

PubMed Central

Borghi, Sergio M.; Pinho-Ribeiro, Felipe A.; Fattori, Victor; Bussmann, Allan J. C.; Vignoli, Josiane A.; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A.

2016-01-01

The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

Balance and muscle power of children with Charcot-Marie-Tooth.

PubMed

Silva, Tais R; Testa, Amanda; Baptista, Cyntia R J A; Marques, Wilson; Mattiello-Sverzut, Ana C

2014-01-01

In certain diseases, functional constraints establish a greater relationship with muscle power than muscle strength. However, in hereditary peripheral polyneuropathies, no such relationship was found in the literature. In children with Charcot-Marie-Tooth (CMT), to identify the impact of muscle strength and range of movement on the static/dynamic balance and standing long jump based on quantitative and functional variables. The study analyzed 19 participants aged between 6 and 16 years, of both genders and with clinical diagnoses of CMT of different subtypes. Anthropometric data, muscle strength of the lower limbs (hand-held dynamometer), ankle and knee range of movement, balance (Pediatric Balance Scale) and standing long jump distance were obtained by standardized procedures. For the statistical analysis, Pearson and Spearman correlation coefficients were used. There was a strong positive correlation between balance and the muscle strength of the right plantar flexors (r=0.61) and dorsiflexors (r=0.59) and a moderate correlation between balance and the muscle strength of inversion (r=0.41) and eversion of the right foot (r=0.44). For the long jump and range of movement, there was a weak positive correlation with right and left plantar flexion (r=0.20 and r=0.12, respectively) and left popliteal angle (r=0.25), and a poor negative correlation with left dorsiflexion (r=-0.15). The data on the patients analyzed suggests that the maintenance of distal muscle strength favors performance during balance tasks, while limitations in the range of movement of the legs seem not to be enough to influence the performance of the horizontal long jump.

Mechanical ventilation induces myokine expression and catabolism in peripheral skeletal muscle in pigs

USDA-ARS?s Scientific Manuscript database

Endotoxin (LPS)-induced sepsis increases circulating cytokines which have been associated with skeletal muscle catabolism. During critical illness, it has been postulated that muscle wasting associated with mechanical ventilation (MV) occurs due to inactivity. We hypothesize that MV and sepsis promo...

Electrophysiological and neuromuscular stability of persons with chronic inflammatory demyelinating polyneuropathy.

PubMed

Gilmore, Kevin J; Allen, Matti D; Doherty, Timothy J; Kimpinski, Kurt; Rice, Charles L

2017-09-01

We assessed motor unit (MU) properties and neuromuscular stability in the tibialis anterior (TA) of chronic inflammatory demyelinating polyneuropathy (CIDP) patients using decomposition-based quantitative electromyography. Dorsiflexion strength was assessed, and surface and concentric needle electromyography were sampled from the TA. Estimates of MU numbers were derived using decomposition-based quantitative electromyography and spike-triggered averaging. Neuromuscular transmission stability was assessed from concentric needle-detected MU potentials. CIDP patients had 43% lower compound muscle action potential amplitude than controls, and despite near-maximum voluntary activation, were 37% weaker. CIDP had 27% fewer functioning MUs in the TA, and had 90% and 44% higher jiggle and jitter values, respectively compared with controls. CIDP had lower strength and compound muscle action potential values, moderately fewer numbers of MUs, and significant neuromuscular instability compared with controls. Thus, in addition to muscle atrophy, voluntary weakness is also due to limitations of peripheral neural transmission consistent with demyelination. Muscle Nerve 56: 413-420, 2017. © 2016 Wiley Periodicals, Inc.

Evidence of isometric function of the flexor hallucis longus muscle in normal gait.

PubMed

Kirane, Y M; Michelson, J D; Sharkey, N A

2008-01-01

Studying mechanics of the muscles spanning multiple joints provides insights into intersegmental dynamics and movement coordination. Multiarticular muscles are thought to function at "near-isometric" lengths to transfer mechanical energy between the adjacent body segments. Flexor hallucis longus (FHL) is a multiarticular flexor of the great toe; however, its potential isometric function has received little attention. We used a robotic loading apparatus to investigate FHL mechanics during simulated walking in cadaver feet, and hypothesized that physiological force transmission across the foot can occur with isometric FHL function. The extrinsic foot tendons, stripped of the muscle fibers, were connected to computer-controlled linear actuators. The FHL activity was controlled using force-feedback (FC) based upon electromyographic data from healthy subjects, and subsequently, isometric positional feedback (PC), maintaining the FHL myotendinous junction stationary during simulated walking. Tendon forces and excursions were recorded, as were the strains within the first metatarsal. Forces in the metatarsal and metatarsophalangeal joint were derived from these strains. The FHL tendon excursion under FC was 6.57+/-3.13mm. The forces generated in the FHL tendon, metatarsal and metatarsophalangeal joint with the FHL under isometric PC were not significantly different in pattern from FC. These observations provide evidence that physiological forces could be generated along the great toe with isometric FHL function. A length servo mechanism such as the stretch reflex could likely control the isometric FHL function during in vivo locomotion; this could have interesting implications regarding the conditions of impaired stretch reflex such as spastic paresis and peripheral neuropathies.

Direct Isolation, Culture and Transplant of Mouse Skeletal Muscle Derived Endothelial Cells with Angiogenic Potential

PubMed Central

Ieronimakis, Nicholas; Balasundaram, Gayathri; Reyes, Morayma

2008-01-01

Background Although diseases associated with microvascular endothelial dysfunction are among the most prevalent illnesses to date, currently no method exists to isolate pure endothelial cells (EC) from skeletal muscle for in vivo or in vitro study. Methodology By utilizing multicolor fluorescent-activated cell sorting (FACS), we have isolated a distinct population of Sca-1+, CD31+, CD34dim and CD45− cells from skeletal muscles of C57BL6 mice. Characterization of this population revealed these cells are functional EC that can be expanded several times in culture without losing their phenotype or capabilities to uptake acetylated low-density lipoprotein (ac-LDL), produce nitric oxide (NO) and form vascular tubes. When transplanted subcutaneously or intramuscularly into the tibialis anterior muscle, EC formed microvessels and integrated with existing vasculature. Conclusion This method, which is highly reproducible, can be used to study the biology and role of EC in diseases such as peripheral vascular disease. In addition this method allows us to isolate large quantities of skeletal muscle derived EC with potential for therapeutic angiogenic applications. PMID:18335025

Skeletal muscle mitochondrial health and spinal cord injury.

PubMed

O'Brien, Laura C; Gorgey, Ashraf S

2016-10-18

Mitochondria are the main source of cellular energy production and are dynamic organelles that undergo biogenesis, remodeling, and degradation. Mitochondrial dysfunction is observed in a number of disease states including acute and chronic central or peripheral nervous system injury by traumatic brain injury, spinal cord injury (SCI), and neurodegenerative disease as well as in metabolic disturbances such as insulin resistance, type II diabetes and obesity. Mitochondrial dysfunction is most commonly observed in high energy requiring tissues like the brain and skeletal muscle. In persons with chronic SCI, changes to skeletal muscle may include remarkable atrophy and conversion of muscle fiber type from oxidative to fast glycolytic, combined with increased infiltration of intramuscular adipose tissue. These changes contribute to a proinflammatory environment, glucose intolerance and insulin resistance. The loss of metabolically active muscle combined with inactivity predisposes individuals with SCI to type II diabetes and obesity. The contribution of skeletal muscle mitochondrial density and electron transport chain activity to the development of the aforementioned comorbidities following SCI is unclear. A better understanding of the mechanisms involved in skeletal muscle mitochondrial dynamics is imperative to designing and testing effective treatments for this growing population. The current editorial will review ways to study mitochondrial function and the importance of improving skeletal muscle mitochondrial health in clinical populations with a special focus on chronic SCI.

(−)-Epicatechin administration and exercising skeletal muscle vascular control and microvascular oxygenation in healthy rats

PubMed Central

Copp, Steven W.; Inagaki, Tadakatsu; White, Michael J.; Hirai, Daniel M.; Ferguson, Scott K.; Holdsworth, Clark T.; Sims, Gabrielle E.; Poole, David C.

2013-01-01

Consumption of the dietary flavanol (−)-epicatechin (EPI) is associated with enhanced endothelial function and augmented skeletal muscle capillarity and mitochondrial volume density. The potential for EPI to improve peripheral vascular function and muscle oxygenation during exercise is unknown. We tested the hypothesis that EPI administration in healthy rats would improve treadmill exercise performance secondary to elevated skeletal muscle blood flow and vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved skeletal muscle microvascular oxygenation. Rats received water (control, n = 12) or 4 mg/kg EPI (n = 12) via oral gavage daily for 24 days. Exercise endurance capacity and peak O2 uptake (V̇o2 peak) were measured via treadmill runs to exhaustion. MAP (arterial catheter) and blood flow (radiolabeled microspheres) were measured and VC was calculated during submaximal treadmill exercise (25 m/min, 5% grade). Spinotrapezius muscle microvascular O2 pressure (Po2mv) was measured (phosphorescence quenching) during electrically induced twitch (1 Hz) contractions. In conscious rats, EPI administration resulted in lower (↓∼5%) resting (P = 0.03) and exercising (P = 0.04) MAP. There were no differences in exercise endurance capacity, V̇o2 peak, total exercising hindlimb blood flow (control, 154 ± 13; and EPI, 159 ± 8 ml·min−1·100 g−1, P = 0.68), or VC (control, 1.13 ± 0.10; and EPI, 1.24 ± 0.08 ml·min−1·100 g−1·mmHg−1, P = 0.21) between groups. Following anesthesia, EPI resulted in lower MAP (↓∼16%) but did not impact resting Po2mv or any kinetics parameters (P > 0.05 for all) during muscle contractions compared with control. EPI administration (4 mg·kg−1·day−1) improved modestly cardiovascular function (i.e., ↓MAP) with no impact on exercise performance, total exercising skeletal muscle blood flow and VC, or contracting muscle microvascular oxygenation in healthy rats. PMID:23144313

(-)-Epicatechin administration and exercising skeletal muscle vascular control and microvascular oxygenation in healthy rats.

PubMed

Copp, Steven W; Inagaki, Tadakatsu; White, Michael J; Hirai, Daniel M; Ferguson, Scott K; Holdsworth, Clark T; Sims, Gabrielle E; Poole, David C; Musch, Timothy I

2013-01-15

Consumption of the dietary flavanol (-)-epicatechin (EPI) is associated with enhanced endothelial function and augmented skeletal muscle capillarity and mitochondrial volume density. The potential for EPI to improve peripheral vascular function and muscle oxygenation during exercise is unknown. We tested the hypothesis that EPI administration in healthy rats would improve treadmill exercise performance secondary to elevated skeletal muscle blood flow and vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved skeletal muscle microvascular oxygenation. Rats received water (control, n = 12) or 4 mg/kg EPI (n = 12) via oral gavage daily for 24 days. Exercise endurance capacity and peak O(2) uptake (Vo(2) peak) were measured via treadmill runs to exhaustion. MAP (arterial catheter) and blood flow (radiolabeled microspheres) were measured and VC was calculated during submaximal treadmill exercise (25 m/min, 5% grade). Spinotrapezius muscle microvascular O(2) pressure (Po(2mv)) was measured (phosphorescence quenching) during electrically induced twitch (1 Hz) contractions. In conscious rats, EPI administration resulted in lower (↓~5%) resting (P = 0.03) and exercising (P = 0.04) MAP. There were no differences in exercise endurance capacity, Vo(2) peak, total exercising hindlimb blood flow (control, 154 ± 13; and EPI, 159 ± 8 ml·min(-1)·100 g(-1), P = 0.68), or VC (control, 1.13 ± 0.10; and EPI, 1.24 ± 0.08 ml·min(-1)·100 g(-1)·mmHg(-1), P = 0.21) between groups. Following anesthesia, EPI resulted in lower MAP (↓~16%) but did not impact resting Po(2mv) or any kinetics parameters (P > 0.05 for all) during muscle contractions compared with control. EPI administration (4 mg·kg(-1)·day(-1)) improved modestly cardiovascular function (i.e., ↓MAP) with no impact on exercise performance, total exercising skeletal muscle blood flow and VC, or contracting muscle microvascular oxygenation in healthy rats.

Functional impairment of skeletal muscle oxidative metabolism during knee extension exercise after bed rest.

PubMed

Salvadego, Desy; Lazzer, Stefano; Marzorati, Mauro; Porcelli, Simone; Rejc, Enrico; Simunic, Bostjan; Pisot, Rado; di Prampero, Pietro Enrico; Grassi, Bruno

2011-12-01

A functional evaluation of skeletal muscle oxidative metabolism during dynamic knee extension (KE) incremental exercises was carried out following a 35-day bed rest (BR) (Valdoltra 2008 BR campaign). Nine young male volunteers (age: 23.5 ± 2.2 yr; mean ± SD) were evaluated. Pulmonary gas exchange, heart rate and cardiac output (by impedance cardiography), skeletal muscle (vastus lateralis) fractional O(2) extraction, and brain (frontal cortex) oxygenation (by near-infrared spectroscopy) were determined during incremental KE. Values at exhaustion were considered "peak". Peak heart rate (147 ± 18 beats/min before vs. 146 ± 17 beats/min after BR) and peak cardiac output (17.8 ± 3.3 l/min before vs. 16.1 ± 1.8 l/min after BR) were unaffected by BR. As expected, brain oxygenation did not decrease during KE. Peak O(2) uptake was lower after vs. before BR, both when expressed as liters per minute (0.99 ± 0.17 vs. 1.26 ± 0.27) and when normalized per unit of quadriceps muscle mass (46.5 ± 6.4 vs. 56.9 ± 11.0 ml·min(-1)·100 g(-1)). Skeletal muscle peak fractional O(2) extraction, expressed as a percentage of the maximal values obtained during a transient limb ischemia, was lower after (46.3 ± 12.1%) vs. before BR (66.5 ± 11.2%). After elimination, by the adopted exercise protocol, of constraints related to cardiovascular O(2) delivery, a decrease in peak O(2) uptake and muscle peak capacity of fractional O(2) extraction was found after 35 days of BR. These findings suggest a substantial impairment of oxidative function at the muscle level, "downstream" with respect to bulk blood flow to the exercising muscles, that is possibly at the level of blood flow distribution/O(2) utilization inside the muscle, peripheral O(2) diffusion, and intracellular oxidative metabolism.

Effect of in situ delivery of acetyl-L-carnitine on peripheral nerve regeneration and functional recovery in transected sciatic nerve in rat.

PubMed

Farahpour, Mohammad Reza; Ghayour, Sina Jangkhahe

2014-12-01

The repair of peripheral nerve injuries is still one of the most challenging tasks and concerns in neurosurgery, plastic and orthopedic surgery. Effect of acetyl-L-carnitine (ALC) loaded chitosan conduit as an in situ delivery system of ALC in bridging the defects was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using a chitosan conduit (CHIT/ALC) filled with 10 μL ALC (100 ng/mL). In control group (CHIT), the conduit was filled with the same volume of the phosphate buffered solution. The regenerated fibers were studied 4, 8, 12 and 16 weeks after surgery. The functional and electrophysiological studies confirmed faster recovery of the regenerated axons in ALC treated than control group (P < 0.05). The mean ratios of gastrocnemius muscles weight were measured. There was statistically significant difference between the muscle weight ratios of CHIT/ALC and CHIT groups (P<0.05). Morphometric indices of regenerated fibers showed number and diameter of the myelinated fibers in CHIT/ALC were significantly higher than in control group. In immuohistochemistry, the location of reactions to S-100 in CHIT/ALC was clearly more positive than CHIT group. ALC when loaded in a chitosan conduit resulted in improvement of functional recovery and quantitative morphometric indices of sciatic nerve. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Contribution of inter-muscular synchronization in the modulation of tremor intensity in Parkinson's disease.

PubMed

He, Xin; Hao, Man-Zhao; Wei, Ming; Xiao, Qin; Lan, Ning

2015-12-01

Involuntary central oscillations at single and double tremor frequencies drive the peripheral neuromechanical system of muscles and joints to cause tremor in Parkinson's disease (PD). The central signal of double tremor frequency was found to correlate more directly to individual muscle EMGs (Timmermann et al. 2003). This study is aimed at investigating what central components of oscillation contribute to inter-muscular synchronization in a group of upper extremity muscles during tremor in PD patients. 11 idiopathic, tremor dominant PD subjects participated in this study. Joint kinematics during tremor in the upper extremity was recorded along with EMGs of six upper arm muscles using a novel experimental apparatus. The apparatus provided support for the upper extremity on a horizontal surface with reduced friction, so that resting tremor in the arm can be recorded with a MotionMonitor II system. In each subject, the frequencies of rhythmic firings in upper arm muscles were determined using spectral analysis. Paired and pool-averaged coherence analyses of EMGs for the group of muscles were performed to correlate the level of inter-muscular synchronization to tremor amplitudes at shoulder and elbow. The phase shift between synchronized antagonistic muscle pairs was calculated to aid coherence analysis in the muscle pool. Recorded EMG revealed that rhythmic firings were present in most recorded muscles, which were either synchronized to form phase-locked bursting cycles at a subject specific frequency, or unsynchronized with a random phase distribution. Paired coherence showed a stronger synchronization among a subset of recorded arm muscles at tremor frequency than that at double tremor frequency. Furthermore, the number of synchronized muscles in the arm was positively correlated to tremor amplitudes at elbow and shoulder. Pool-averaged coherence at tremor frequency also showed a better correlation with the amplitude of resting tremor than that of double tremor frequency, indicating that the neuromechanical coupling in peripheral neuromuscular system was stronger at tremor frequency. Both paired and pool-averaged coherences are more consistent indexes to correlate to tremor intensity in a group of upper extremity muscles of PD patients. The central drive at tremor frequency contributes mainly to synchronize peripheral muscles in the modulation of tremor intensity.

Idiopathic and diabetic skeletal muscle necrosis: evaluation by magnetic resonance imaging.

PubMed

Kattapuram, Taj M; Suri, Rajeev; Rosol, Michael S; Rosenberg, Andrew E; Kattapuram, Susan V

2005-04-01

Idiopathic and diabetic-associated muscle necrosis are similar, uncommon clinical entities requiring conservative management and minimal intervention to avoid complications and prolonged hospitalization. An early noninvasive diagnosis is therefore essential. We evaluated the magnetic resonance imaging (MRI) characteristics of muscle necrosis in 14 patients, in eight of whom the diagnoses were confirmed histologically. Two experienced musculoskeletal radiologists performed retrospective evaluations of the MRI studies of 14 patients with the diagnoses of skeletal muscle infarction. In 10 cases gadolinium-enhanced (T1-weighted fat-suppressed) sequences were available along with T1-weighted, T2-weighted images and STIR sequences, while in four cases contrast-enhanced images were not available. Eight patients had underlying diabetes and in six patients the cause of the myonecrosis was considered idiopathic. T1-weighted images demonstrated isointense swelling of the involved muscle, with mildly displaced fascial planes. There was effacement of the fat signal intensity within the muscle. Fat-suppressed T2-weighted images showed diffuse heterogeneous high signal intensity in the muscles suggestive of edema. Perifascial fluid collection was seen in eight cases. Subcutaneous edema was present in seven patients. Following intravenous gadolinium administration, MRI demonstrated a focal area of heterogeneously enhancing mass with peripheral enhancement. Within this focal lesion, linear dark areas were seen with serpentine enhancing streaks separating them in eight cases. In two cases, a central relatively nonenhancing mass with irregular margins and peripheral enhancement was noted. The peripheral enhancement involved a significant part of the muscle. No focal fluid collection was noted. We believe that the constellation of imaging findings on T1- and T2-weighted images and post-gadolinium sequences is highly suggestive of muscle necrosis. We consider certain specific findings on gadolinium-enhanced images to be characteristic. The findings reported here should provide radiologists with useful information in making the diagnosis of skeletal muscle necrosis without resorting to invasive procedures.

Transplantation of autologous peripheral blood mononuclear cells in the subarachnoid space for amyotrophic lateral sclerosis: a safety analysis of 14 patients

PubMed Central

Li, Xiao-yan; Liang, Zhan-hua; Han, Chao; Wei, Wen-juan; Song, Chun-li; Zhou, Li-na; Liu, Yang; Li, Ying; Ji, Xiao-fei; Liu, Jing

2017-01-01

There is a small amount of clinical data regarding the safety and feasibility of autologous peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis. The objectives of this retrospective study were to assess the safety and efficacy of peripheral blood mononuclear cell transplantation in 14 amyotrophic lateral sclerosis patients to provide more objective data for future clinical trials. After stem cell mobilization and collection, autologous peripheral blood mononuclear cells (1 × 109) were isolated and directly transplanted into the subarachnoid space of amyotrophic lateral sclerosis patients. The primary outcome measure was incidence of adverse events. Secondary outcome measures were electromyography 1 week before operation and 4 weeks after operation, Functional Independence Measurement, Berg Balance Scale, and Dysarthria Assessment Scale 1 week preoperatively and 1, 2, 4 and 12 weeks postoperatively. There was no immediate or delayed transplant-related cytotoxicity. The number of leukocytes, serum alanine aminotransferase and creatinine levels, and body temperature were within the normal ranges. Radiographic evaluation showed no serious transplant-related adverse events. Muscle strength grade, results of Functional Independence Measurement, Berg Balance Scale, and Dysarthria Assessment Scale were not significantly different before and after treatment. These findings suggest that peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis is safe, but its therapeutic effect is not remarkable. Thus, a large-sample investigation is needed to assess its efficacy further. PMID:28469667

Position Sense in Chronic Pain: Separating Peripheral and Central Mechanisms in Proprioception in Unilateral Limb Pain.

PubMed

Tsay, Anthony J; Giummarra, Melita J

2016-07-01

Awareness of limb position is derived primarily from muscle spindles and higher-order body representations. Although chronic pain appears to be associated with motor and proprioceptive disturbances, it is not clear if this is due to disturbances in position sense, muscle spindle function, or central representations of the body. This study examined position sense errors, as an indicator of spindle function, in participants with unilateral chronic limb pain. The sample included 15 individuals with upper limb pain, 15 with lower limb pain, and 15 sex- and age-matched pain-free control participants. A 2-limb forearm matching task in blindfolded participants, and a single-limb pointer task, with the reference limb hidden from view, was used to assess forearm position sense. Position sense was determined after muscle contraction or stretch, intended to induce a high or low spindle activity in the painful and nonpainful limbs, respectively. Unilateral upper and lower limb chronic pain groups produced position errors comparable with healthy control participants for position matching and pointer tasks. The results indicate that the painful and nonpainful limb are involved in limb-matching. Lateralized pain, whether in the arm or leg, does not influence forearm position sense. Painful and nonpainful limbs are involved in bilateral limb-matching. Muscle spindle function appears to be preserved in the presence of chronic pain. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Oral N-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease.

PubMed

Hirai, Daniel M; Jones, Joshua H; Zelt, Joel T; da Silva, Marianne L; Bentley, Robert F; Edgett, Brittany A; Gurd, Brendon J; Tschakovsky, Michael E; O'Donnell, Denis E; Neder, J Alberto

2017-05-01

Heightened oxidative stress is implicated in the progressive impairment of skeletal muscle vascular and mitochondrial function in chronic obstructive pulmonary disease (COPD). Whether accumulation of reactive oxygen species contributes to exercise intolerance in the early stages of COPD is unknown. The purpose of the present study was to determine the effects of oral antioxidant treatment with N -acetylcysteine (NAC) on respiratory, cardiovascular, and locomotor muscle function and exercise tolerance in patients with mild COPD. Thirteen patients [forced expiratory volume in 1 s (FEV 1 )-to-forced vital capacity ratio < lower limit of normal (LLN) and FEV 1 ≥ LLN) were enrolled in a double-blind, randomized crossover study to receive NAC (1,800 mg/day) or placebo for 4 days. Severe-intensity constant-load exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary ventilation and gas exchange, quadriceps muscle oxygenation (near-infrared spectroscopy), and estimated capillary blood flow. Nine patients completed the study with no major adverse clinical effects. Although NAC elevated plasma glutathione by ~27% compared with placebo ( P < 0.05), there were no differences in exercise tolerance (placebo: 325 ± 47 s, NAC: 336 ± 51 s), central hemodynamics, arterial blood pressure, pulmonary ventilation or gas exchange, locomotor muscle oxygenation, or capillary blood flow from rest to exercise between conditions ( P > 0.05 for all). In conclusion, modulation of plasma redox status with oral NAC treatment was not translated into beneficial effects on central or peripheral components of the oxygen transport pathway, thereby failing to improve exercise tolerance in nonhypoxemic patients with mild COPD. NEW & NOTEWORTHY Acute antioxidant treatment with N -acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or peripheral components of the O 2 transport pathway, thereby failing to improve exercise tolerance in patients with mild chronic obstructive pulmonary disease (COPD). Copyright © 2017 the American Physiological Society.

Gait deficiencies associated with peripheral artery disease are different than chronic obstructive pulmonary disease.

PubMed

McCamley, John D; Pisciotta, Eric J; Yentes, Jennifer M; Wurdeman, Shane R; Rennard, Stephen I; Pipinos, Iraklis I; Johanning, Jason M; Myers, Sara A

2017-09-01

Previous studies have indicated that patients with peripheral artery disease (PAD), display significant differences in their kinetic and kinematic gait characteristics when compared to healthy, aged-matched controls. The ability of patients with chronic obstructive pulmonary disease (COPD) to ambulate is also limited. These limitations are likely due to pathology-driven muscle morphology and physiology alterations establish in PAD and COP, respectively. Gait changes in PAD were compared to gait changes due to COPD to further understand how altered limb muscle due to disease can alter walking patterns. Both groups were independently compared to healthy controls. It was hypothesized that both patients with PAD and COPD would demonstrate similar differences in gait when compared to healthy controls. Patients with PAD (n=25), patients with COPD (n=16), and healthy older control subjects (n=25) performed five walking trials at self-selected speeds. Sagittal plane joint kinematic and kinetic group means were compared. Peak values for hip flexion angle, braking impulse, and propulsive impulse were significantly reduced in patients with symptomatic PAD compared to patients with COPD. After adjusting for walking velocity, significant reductions (p<0.05) in the peak values for hip flexion angle, dorsiflexor moment, ankle power generation, propulsion force, braking impulse, and propulsive impulse were found in patients with PAD compared to healthy controls. No significant differences were observed between patients with COPD and controls. The results of this study demonstrate that while gait patterns are impaired for patients with PAD, this is not apparent for patients with COPD (without PAD). PAD (without COPD) causes changes to the muscle function of the lower limbs that affects gait even when subjects walk from a fully rested state. Altered muscle function in patients with COPD does not have a similar effect. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of trophic factors' expression between paralyzed and recovering muscles after facial nerve injury. A quantitative analysis in time course.

PubMed

Grosheva, Maria; Nohroudi, Klaus; Schwarz, Alisa; Rink, Svenja; Bendella, Habib; Sarikcioglu, Levent; Klimaschewski, Lars; Gordon, Tessa; Angelov, Doychin N

2016-05-01

After peripheral nerve injury, recovery of motor performance negatively correlates with the poly-innervation of neuromuscular junctions (NMJ) due to excessive sprouting of the terminal Schwann cells. Denervated muscles produce short-range diffusible sprouting stimuli, of which some are neurotrophic factors. Based on recent data that vibrissal whisking is restored perfectly during facial nerve regeneration in blind rats from the Sprague Dawley (SD)/RCS strain, we compared the expression of brain derived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF2), insulin growth factors 1 and 2 (IGF1, IGF2) and nerve growth factor (NGF) between SD/RCS and SD-rats with normal vision but poor recovery of whisking function after facial nerve injury. To establish which trophic factors might be responsible for proper NMJ-reinnervation, the transected facial nerve was surgically repaired (facial-facial anastomosis, FFA) for subsequent analysis of mRNA and proteins expressed in the levator labii superioris muscle. A complicated time course of expression included (1) a late rise in BDNF protein that followed earlier elevated gene expression, (2) an early increase in FGF2 and IGF2 protein after 2 days with sustained gene expression, (3) reduced IGF1 protein at 28 days coincident with decline of raised mRNA levels to baseline, and (4) reduced NGF protein between 2 and 14 days with maintained gene expression found in blind rats but not the rats with normal vision. These findings suggest that recovery of motor function after peripheral nerve injury is due, at least in part, to a complex regulation of lesion-associated neurotrophic factors and cytokines in denervated muscles. The increase of FGF-2 protein and concomittant decrease of NGF (with no significant changes in BDNF or IGF levels) during the first week following FFA in SD/RCS blind rats possibly prevents the distal branching of regenerating axons resulting in reduced poly-innervation of motor endplates. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of a Regenerative Peripheral Nerve Interface for Control of a Neuroprosthetic Limb.

PubMed

Urbanchek, Melanie G; Kung, Theodore A; Frost, Christopher M; Martin, David C; Larkin, Lisa M; Wollstein, Adi; Cederna, Paul S

2016-01-01

Background. The purpose of this experiment was to develop a peripheral nerve interface using cultured myoblasts within a scaffold to provide a biologically stable interface while providing signal amplification for neuroprosthetic control and preventing neuroma formation. Methods. A Regenerative Peripheral Nerve Interface (RPNI) composed of a scaffold and cultured myoblasts was implanted on the end of a divided peroneal nerve in rats (n = 25). The scaffold material consisted of either silicone mesh, acellular muscle, or acellular muscle with chemically polymerized poly(3,4-ethylenedioxythiophene) conductive polymer. Average implantation time was 93 days. Electrophysiological tests were performed at endpoint to determine RPNI viability and ability to transduce neural signals. Tissue samples were examined using both light microscopy and immunohistochemistry. Results. All implanted RPNIs, regardless of scaffold type, remained viable and displayed robust vascularity. Electromyographic activity and stimulated compound muscle action potentials were successfully recorded from all RPNIs. Physiologic efferent motor action potentials were detected from RPNIs in response to sensory foot stimulation. Histology and transmission electron microscopy revealed mature muscle fibers, axonal regeneration without neuroma formation, neovascularization, and synaptogenesis. Desmin staining confirmed the preservation and maturation of myoblasts within the RPNIs. Conclusions. RPNI demonstrates significant myoblast maturation, innervation, and vascularization without neuroma formation.

Summary of Research Adaptions of Visceral and Cerebral Resistance Arteries to Simulated Microgravity

NASA Technical Reports Server (NTRS)

Delp, Michael

2003-01-01

The proposed studies were designed address the effects of simulated microgravity on vascular smooth muscle and endothelial cell function in resistance arteries isolated from visceral tissues (spleen, mesentery and kidneys) and cerebrum. Alterations in vascular function induced by microgravity are particularly relevant to the problems of orthostatic intolerance and reduced exercise capacity experienced by astronauts upon re-entry into the earth's gravitational field. Decrements in contractile function or enhanced vasodilatory responsiveness of peripheral resistance arteries could lead to decreased peripheral resistance and orthostatic hypotension. Alternatively, augmentation of contractile function in cerebral resistance arteries could lead to increased cerebral vascular resistance and diminished perfusion of the brain. The Specific Aims and hypotheses were proposed in this grant. Following each of the Specific Aims, progress toward addressing that specific aim is presented. With the exception of Specific Aim VI (see aim for details), all aims have been experimentally addressed as proposed. The final six months of the granting period will be used for manuscript preparation; manuscripts in preparation will contain results from Specific Aims I-IV. Results from Specific Aims V and VI have been published.

Peripheral Nerve Disorders

MedlinePlus

... outlet syndrome. In some cases, like complex regional pain syndrome and brachial plexus injuries, the problem begins after an injury. Some people are born with peripheral nerve disorders. Symptoms often start gradually, and then ... Burning or tingling Muscle weakness Sensitivity to touch ...

Identification of PN1, a Predominant Voltage-Dependent Sodium Channel Expressed Principally in Peripheral Neurons

NASA Astrophysics Data System (ADS)

Toledo-Aral, Juan J.; Moss, Brenda L.; He, Zhi-Jun; Koszowski, Adam G.; Whisenand, Teri; Levinson, Simon R.; Wolf, John J.; Silos-Santiago, Inmaculada; Halegoua, Simon; Mandel, Gail

1997-02-01

Membrane excitability in different tissues is due, in large part, to the selective expression of distinct genes encoding the voltage-dependent sodium channel. Although the predominant sodium channels in brain, skeletal muscle, and cardiac muscle have been identified, the major sodium channel types responsible for excitability within the peripheral nervous system have remained elusive. We now describe the deduced primary structure of a sodium channel, peripheral nerve type 1 (PN1), which is expressed at high levels throughout the peripheral nervous system and is targeted to nerve terminals of cultured dorsal root ganglion neurons. Studies using cultured PC12 cells indicate that both expression and targeting of PN1 is induced by treatment of the cells with nerve growth factor. The preferential localization suggests that the PN1 sodium channel plays a specific role in nerve excitability.

Biofeedback-assisted relaxation training to decrease test anxiety in nursing students.

PubMed

Prato, Catherine A; Yucha, Carolyn B

2013-01-01

Nursing students experiencing debilitating test anxiety may be unable to demonstrate their knowledge and have potential for poor academic performance. A biofeedback-assisted relaxation training program was created to reduce test anxiety. Anxiety was measured using Spielberger's Test Anxiety Inventory and monitoring peripheral skin temperature, pulse, and respiration rates during the training. Participants were introduced to diaphragmatic breathing, progressive muscle relaxation, and autogenic training. Statistically significant changes occurred in respiratory rates and skin temperatures during the diaphragmatic breathing session; respiratory rates and peripheral skin temperatures during progressive muscle relaxation session; respiratory and pulse rates, and peripheral skin temperatures during the autogenic sessions. No statistically significant difference was noted between the first and second TAI. Subjective test anxiety scores of the students did not decrease by the end of training. Autogenic training session was most effective in showing a statistically significant change in decreased respiratory and pulse rates and increased peripheral skin temperature.

Selective activation of human soleus and medial gastrocnemius muscles during walking in water.

PubMed

Miyoshi, T; Satoh, T; Nakazawa, K; Komeda, T; Yano, H

2000-07-01

During walking in water (WW) the vertical component of ground reaction forces decreases, while the greater propulsive force is required to move forward against the greater resistance of water. In such reduced gravity environment, Hutchison et al. (1989) have demonstrated that the relative activation of rat medial gastrocnemius (MGAS) increased compared to that of the soleus (SOL) during swimming, suggesting different effects of peripheral information on motoneuron excitability of these muscles. It is conceivable that both buoyancy and resistance of water have different effects on the activation patterns of triceps surae muscles during WW, since the reduced weight in water might decrease the peripheral inflow relating load information while greater volitional command might be needed to propel a body forward against the water resistance. The present study was designed to assess each peripheral inflow and efferent input by adjusting the load and walking speed voluntarily during WW. The aim of this study is to investigate the dissociative activation pattern between the SOL and the MGAS during WW.

Peripheral T-cell lymphoma with unusual clinical presentation of rhabdomyolysis.

PubMed

Liu, Zhiyu; Medeiros, L Jeffrey; Young, Ken H

2017-03-01

Primary extranodal lymphoma is known to occur in nose, gastrointestinal tract, skin, bone, and central nervous system. However, it is extremely rare for primary lymphoma to arise in skeletal muscle. We report a case of a 32-year-old man who presented initially with fever and fatigue. He had a history of alcohol abuse. Laboratory studies and computerized tomography scan showed results consistent with rhabdomyolysis, but the cause of the rhabdomyolysis was undetermined. After biopsy of abdominal skeletal muscle with histologic examination and T-cell receptor gamma chain gene rearrangement analysis, the diagnosis of peripheral T-cell lymphoma was established. After two cycles of the cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide regimen, the patient's symptoms greatly improved. This is the third reported case of peripheral T-cell lymphoma arising in skeletal muscle reported in the literature and which presented clinically with rhabdomyolysis. The alcohol abuse during the clinical course likely worsens the pathologic process of the rhabdomyolysis. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

[Intramuscular injection of lentivirus-mediated EPAS1 gene improves hind limb ischemia and its mechanism in a rat model of peripheral artery vascular disease].

PubMed

Wang, Zhihong; Gu, Hongbin; Yang, Fan; Xie, Huajie; Sheng, Lei; Li, Mingfei

2017-11-01

Objective To investigate the effect of over-expressed endothelial Per-Arnt-Sim domain protein 1 (EPAS1) on peripheral arterial disease (PAD) in a rat model. Methods PAD rat model was established by external iliac artery ligation followed by lentivirus-mediated EPAS1 gene injection into rat right adductor magnus. The models were evaluated by quantitative analysis of gait disturbance. The changes of blood flow in the posterior extremity of the rats were detected using laser Doppler. The expressions of EPAS1, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) mRNAs were tested by real-time quantitative PCR. The expression of α-smooth muscle actin (αSMA) was detected by immunohistochemical staining. Results Compared with lenti-EGFP group, rat hind limb function and circulation got recovered obviously 7 days after lenti-EPAS1 injection. The mRNA expressions of EPAS1, HGF, bFGF, and VEGF were up-regulated in the lenti-EPAS1-treated sites.The expression of αSMA showed an obvious increase in the lenti-EPAS1-treated muscles. Conclusion Over-expressed lenti-EPAS1 can promote angiogenesis via the up-regulation of EPAS1-related angiogenic factors in the muscles of the affected hind limb and reduce gait disturbance.

Effects that passive cycling exercise have on muscle strength, duration of mechanical ventilation, and length of hospital stay in critically ill patients: a randomized clinical trial

PubMed Central

Machado, Aline dos Santos; Pires-Neto, Ruy Camargo; Carvalho, Maurício Tatsch Ximenes; Soares, Janice Cristina; Cardoso, Dannuey Machado; de Albuquerque, Isabella Martins

2017-01-01

ABSTRACT Objective: To evaluate the effects that passive cycling exercise, in combination with conventional physical therapy, have on peripheral muscle strength, duration of mechanical ventilation, and length of hospital stay in critically ill patients admitted to the ICU of a tertiary care university hospital. Methods: This was a randomized clinical trial involving 38 patients (≥ 18 years of age) on mechanical ventilation who were randomly divided into two groups: control (n = 16), receiving conventional physical therapy; and intervention (n = 22), receiving conventional physical therapy and engaging in passive cycling exercise five days per week. The mean age of the patients was 46.42 ± 16.25 years, and 23 were male. The outcomes studied were peripheral muscle strength, as measured by the Medical Research Council scale, duration of mechanical ventilation, and length of hospital stay. Results: There was a significant increase in peripheral muscle strength (baseline vs. final) in both groups (control: 40.81 ± 7.68 vs. 45.00 ± 6.89; and intervention: 38.73 ± 11.11 vs. 47.18 ± 8.75; p < 0.001 for both). However, the range of increase in strength was higher in the intervention group than in the control group (8.45 ± 5.20 vs. 4.18 ± 2.63; p = 0.005). There were no significant differences between the groups in terms of duration of mechanical ventilation or length of hospital stay. Conclusions: The results suggest that the performance of continuous passive mobilization on a cyclical basis helps to recover peripheral muscle strength in ICU patients. (ClinicalTrials.gov Identifier: NCT01769846 [http://www.clinicaltrials.gov/]) PMID:28538781

Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats.

PubMed

Jensen, Vivi F H; Molck, Anne-Marie; Soeborg, Henrik; Nowak, Jette; Chapman, Melissa; Lykkesfeldt, Jens; Bogh, Ingrid B

2018-01-01

Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery period in some of the animals. Sciatic, plantar nerves and thigh muscle were examined histopathologically after four or eight weeks of infusion and after the recovery period. IIH resulted in high incidence of axonal degeneration in sciatic nerves and low incidence in plantar nerves indicating proximo-distal progression of the neuropathy. The neuropathy progressed in severity (sciatic nerve) and incidence (sciatic and plantar nerve) with the duration of IIH. The myopathy consisted of groups of angular atrophic myofibres which resembled histopathologic changes classically seen after denervation of skeletal muscle, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses proximo-distally, that severity and incidence increase with duration of the hypoglycaemia and that these changes are partially reversible within four weeks. Furthermore, IIH-induced myopathy is most likely secondary to the neuropathy. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Rehabilitation of a marathon runner with Guillain-Barré syndrome.

PubMed

Fisher, Tara Beth; Stevens, Jennifer E

2008-12-01

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculoneuropathy that affects nerve roots and peripheral nerves leading to motor neuropathy and flaccid paralysis. This case report describes the physical therapy examination, intervention, and outcomes for a marathon runner with GBS. The patient was a 30-year-old male marathon runner who presented with acutely evolving motor and sensory deficits that initially stabilized and then worsened. Both GBS and chronic inflammatory demyelinating polyradiculoneuropathy were considered as diagnoses, and medical treatment included a combination of intravenous administration of immunoglobulins, plasmapheresis, and corticosteroids. During his stay in an acute inpatient rehabilitation facility, the intervention was focused on regaining functional independence and strength with care not to induce fatigue or relapse. After three weeks in an acute inpatient rehabilitation facility, the patient showed marked gains in Functional Independence Measure scores and muscle performance as measured by manual muscle testing.

[Experimental studies for the improvement of facial nerve regeneration].

PubMed

Guntinas-Lichius, O; Angelov, D N

2008-02-01

Using a combination of the following, it is possible to investigate procedures to improve the morphological and functional regeneration of the facial nerve in animal models: 1) retrograde fluorescence tracing to analyse collateral axonal sprouting and the selectivity of reinnervation of the mimic musculature, 2) immunohistochemistry to analyse both the terminal axonal sprouting in the muscles and the axon reaction within the nucleus of the facial nerve, the peripheral nerve, and its environment, and 3) digital motion analysis of the muscles. To obtain good functional facial nerve regeneration, a reduction of terminal sprouting in the mimic musculature seems to be more important than a reduction of collateral sprouting at the lesion site. Promising strategies include acceleration of nerve regeneration, forced induced use of the paralysed face, mechanical stimulation of the face, and transplantation of nerve-growth-promoting olfactory epithelium at the lesion site.

The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Easterling, K.J.; Trumble, T.E.

1990-10-01

Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively).more » Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.« less

The OTOLITH Experiment - Assessment of Otolith Function During Postflight Re-adaption

NASA Technical Reports Server (NTRS)

Clarke, A. H.; Wood, S. J.; Schoenfeld, U.

2010-01-01

The ongoing "Otolith" experiment is designed to comprehensively assess the otolith function during the re-adaptation phase after spaceflight. The novel protocol includes unilateral testing of each of the two otolith organs the utricle and the saccule. To assess utricle function, the otolith-ocular response (OOR) and the subjective visual vertical (SVV) are measured during unilateral centrifugation, which permits independent stimulation of the right and left ear. Measurement of the unilateral otolith-ocular response (uOOR) yields information on the response behaviour of the right and left peripheral utricles, whereas the SVV reflects the behaviour of the entire pathway from the peripheral otolith receptors to the vestibular cortex. Thus, by comparative evaluation of the results from the two tests, the degree of peripheral versus central adaptation during the post-flight period can be determined. To assess unilateral saccule function, vestibular evoked myogenic potentials (VEMP) are recorded. Since the saccules are predominantly aligned to gravity, and interplay with the antigravity muscles, it is hypothesised that these potentials shall be altered after spaceflight. To date the study has been conducted with 5 of a planned 8 short-flight Shuttle astronauts. Preliminary results will be discussed together with those from clinical studies of dizziness patients, where the same test protocol is employed. ACKNOWLEDGEMENT This work is supported by the German Aerospace Center (Grant DLR W130729) and is conducted under the auspices of ESA, in cooperation with NASA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joo, Hyung Joon; Seo, Ha-Rim; Jeong, Hyo Eun

Highlights: • Two distinct vascular progenitor cells are induced from adult peripheral blood. • ECFCs induce vascular structures in vitro and in vivo. • SMPCs augment the in vitro and in vivo angiogenic potential of ECFCs. • Both cell types have synergistic therapeutic potential in ischemic hindlimb model. - Abstract: Proangiogenic cell therapy using autologous progenitors is a promising strategy for treating ischemic disease. Considering that neovascularization is a harmonized cellular process that involves both endothelial cells and vascular smooth muscle cells, peripheral blood-originating endothelial colony-forming cells (ECFCs) and smooth muscle progenitor cells (SMPCs), which are similar to mature endothelialmore » cells and vascular smooth muscle cells, could be attractive cellular candidates to achieve therapeutic neovascularization. We successfully induced populations of two different vascular progenitor cells (ECFCs and SMPCs) from adult peripheral blood. Both progenitor cell types expressed endothelial-specific or smooth muscle-specific genes and markers, respectively. In a protein array focused on angiogenic cytokines, SMPCs demonstrated significantly higher expression of bFGF, EGF, TIMP2, ENA78, and TIMP1 compared to ECFCs. Conditioned medium from SMPCs and co-culture with SMPCs revealed that SMPCs promoted cell proliferation, migration, and the in vitro angiogenesis of ECFCs. Finally, co-transplantation of ECFCs and SMPCs induced robust in vivo neovascularization, as well as improved blood perfusion and tissue repair, in a mouse ischemic hindlimb model. Taken together, we have provided the first evidence of a cell therapy strategy for therapeutic neovascularization using two different types of autologous progenitors (ECFCs and SMPCs) derived from adult peripheral blood.« less

[Age-related features of neuromuscular function in rats with hyperthyroidism].

PubMed

Nerush, P O; Makiĭ, Ie A; Rodyns'kyĭ, O H

2001-01-01

Studied features of functioning of nervous-muscular system at white rats of two age groups: preadolescent (5 weeks) and puberal (24 weeks), in conditions experimental hyperthyroidism (HT). It is established, that in conditions HT at action of the raised concentration thyroxine characteristics of excitation gastrocnemius muscles essentially changed at irritation of a sciatic nerve in groups preadolescent and puberal animals. In all age groups in conditions HT increase of a threshold of excitation gastrocnemius muscles is marked at indirect stimulation and decrease at direct stimulation; also in all age groups in conditions HT reduction of time chronaxy muscles is fixed, both at direct, and at indirect irritation. At preadolescent animals, as against puberal in conditions HT at action of the raised concentration thyroxine on nervous-muscular system it is not revealed authentic change of the latent period and amplitude of potential of action (PA). The conclusion is made, that in conditions HT change of a threshold of excitation and chronaxy gastrocnemius muscles both at direct, and at indirect irritation do not carry age specificity and have an identical orientation, both at preadolescent, and at puberal rats. At preadolescent animals in conditions HT, as against puberal the parameter of amplitude and latent period PA authentically did not change, that can testify to smaller sensitivity of the caused answers gastrocnemius muscles to the raised concentration thyroxine, probably, by virtue of immaturity peripheral neuromotor the device.

Influence of peripheral magnetic stimulation of soleus muscle on H and M waves.

PubMed

Matsuda, Tadamitsu; Kurayama, Taichi; Tagami, Miki; Fujino, Yuji; Manji, Atsushi; Kusumoto, Yasuaki; Amimoto, Kazu

2018-05-01

[Purpose] This study evaluated the effects of repetitive peripheral magnetic stimulation of the soleus muscle on spinal cord and peripheral motor nerve excitability. [Subjects and Methods] Twelve healthy adults (mean age 22 years) who provided written informed consent were administered repetitive peripheral magnetic stimulation for 10 min. Pre-and post-stimulation latencies and amplitudes of H- and M-waves of the soleus muscle were measured using electromyography and compared using paired t-tests. [Results] Pre- and post-stimulation latencies (28.3 ± 3.3 vs. 29.1 ± 1.3 ms, respectively) and amplitudes (35.8 ± 1.3 vs. 35.8 ± 1.1 mV, respectively) of H-waves were similar. Pre-stimulation latencies of M-waves were significantly higher than post-stimulation latencies (6.1 ± 2.2 vs. 5.0 ± 0.9 ms, respectively), although pre- and post-stimulation amplitudes were similar (12.2 ± 1.4 vs. 12.2 ± 1.3 mV, respectively). Motor neuron excitability, based on the excitability of motor nerves and peripheral nerve action, was increased by M-waves following magnetic stimulation. [Conclusion] The lack of effect of magnetic stimulation on the amplitude and latency of the H-reflex suggests that magnetic stimulation did not activate sensory nerve synapses of α motor neurons in the spinal cord. However, because motor nerves were stimulated together with sensory nerves, the increased H-wave amplitude may have reflected changes in peripheral rather than in α motor nerves.

Protein alterations in women with chronic widespread pain--An explorative proteomic study of the trapezius muscle.

PubMed

Olausson, Patrik; Gerdle, Björn; Ghafouri, Nazdar; Sjöström, Dick; Blixt, Emelie; Ghafouri, Bijar

2015-07-07

Chronic widespread pain (CWP) has a high prevalence in the population and is associated with prominent negative individual and societal consequences. There is no clear consensus concerning the etiology behind CWP although alterations in the central processing of nociception maintained by peripheral nociceptive input has been suggested. Here, we use proteomics to study protein changes in trapezius muscle from 18 female patients diagnosed with CWP compared to 19 healthy female subjects. The 2-dimensional gel electrophoresis (2-DE) in combination with multivariate statistical analyses revealed 17 proteins to be differently expressed between the two groups. Proteins were identified by mass spectrometry. Many of the proteins are important enzymes in metabolic pathways like the glycolysis and gluconeogenesis. Other proteins are associated with muscle damage, muscle recovery, stress and inflammation. The altered expressed levels of these proteins suggest abnormalities and metabolic changes in the myalgic trapezius muscle in CWP. Taken together, this study gives further support that peripheral factors may be of importance in maintaining CWP.

Protein alterations in women with chronic widespread pain – An explorative proteomic study of the trapezius muscle

PubMed Central

Olausson, Patrik; Gerdle, Björn; Ghafouri, Nazdar; Sjöström, Dick; Blixt, Emelie; Ghafouri, Bijar

2015-01-01

Chronic widespread pain (CWP) has a high prevalence in the population and is associated with prominent negative individual and societal consequences. There is no clear consensus concerning the etiology behind CWP although alterations in the central processing of nociception maintained by peripheral nociceptive input has been suggested. Here, we use proteomics to study protein changes in trapezius muscle from 18 female patients diagnosed with CWP compared to 19 healthy female subjects. The 2-dimensional gel electrophoresis (2-DE) in combination with multivariate statistical analyses revealed 17 proteins to be differently expressed between the two groups. Proteins were identified by mass spectrometry. Many of the proteins are important enzymes in metabolic pathways like the glycolysis and gluconeogenesis. Other proteins are associated with muscle damage, muscle recovery, stress and inflammation. The altered expressed levels of these proteins suggest abnormalities and metabolic changes in the myalgic trapezius muscle in CWP. Taken together, this study gives further support that peripheral factors may be of importance in maintaining CWP. PMID:26150212

Redistribution of Cav2.1 channels and calcium ions in nerve terminals following end-to-side neurorrhaphy: ionic imaging analysis by TOF-SIMS.

PubMed

Liu, Chiung-Hui; Chang, Hung-Ming; Tseng, To-Jung; Lan, Chyn-Tair; Chen, Li-You; Youn, Su-Chung; Lee, Jian-Jr; Mai, Fu-Der; Chou, Jui-Feng; Liao, Wen-Chieh

2016-11-01

The P/Q-type voltage-dependent calcium channel (Cav2.1) in the presynaptic membranes of motor nerve terminals plays an important role in regulating Ca 2+ transport, resulting in transmitter release within the nervous system. The recovery of Ca 2+ -dependent signal transduction on motor end plates (MEPs) and innervated muscle may directly reflect nerve regeneration following peripheral nerve injury. Although the functional significance of calcium channels and the levels of Ca 2+ signalling in nerve regeneration are well documented, little is known about calcium channel expression and its relation with the dynamic Ca 2+ ion distribution at regenerating MEPs. In the present study, end-to-side neurorrhaphy (ESN) was performed as an in vivo model of peripheral nerve injury. The distribution of Ca 2+ at regenerating MEPs following ESN was first detected by time-of-flight secondary ion mass spectrometry, and the specific localization and expression of Cav2.1 channels were examined by confocal microscopy and western blotting. Compared with other fundamental ions, such as Na + and K + , dramatic changes in the Ca 2+ distribution were detected along with the progression of MEP regeneration. The re-establishment of Ca 2+ distribution and intensity were correlated with the functional recovery of muscle in ESN rats. Furthermore, the re-clustering of Cav2.1 channels after ESN at the nerve terminals corresponded with changes in the Ca 2+ distribution. These results indicated that renewal of the Cav2.1 distribution within the presynaptic nerve terminals may be necessary for initiating a proper Ca 2+ influx and shortening the latency of muscle contraction during nerve regeneration.

Neuromuscular diseases: Diagnosis and management.

PubMed

Mary, P; Servais, L; Vialle, R

2018-02-01

Neuromuscular diseases (NMDs) affect the peripheral nervous system, which includes the motor neurons and sensory neurons; the muscle itself; or the neuromuscular junction. Thus, the term NMDs encompasses a vast array of different syndromes. Some of these syndromes are of direct relevance to paediatric orthopaedic surgeons, either because the presenting manifestation is a functional sign (e.g., toe-walking) or deformity (e.g., pes cavus or scoliosis) suggesting a need for orthopaedic attention or because orthopaedic abnormalities requiring treatment develop during the course of a known NMD. The main NMDs relevant to the orthopaedic surgeon are infantile spinal muscular atrophy (a motor neuron disease), peripheral neuropathies (chiefly, Charcot-Marie-Tooth disease), congenital muscular dystrophies, progressive muscular dystrophies, and Steinert myotonic dystrophy (or myotonic dystrophy type 1). Muscle weakness is a symptom shared by all these conditions. The paediatric orthopaedic surgeon must be familiar, not only with the musculoskeletal system, but also with many other domains (particularly respiratory and cardiac function and nutrition) that may interfere with the treatment and require preoperative management. Good knowledge of the natural history of each NMD is essential to ensure optimal timing of the therapeutic interventions, which must be performed under the best possible conditions in these usually frail patients. Timing is particularly crucial for the treatment of spinal deformities due to paraspinal muscle hypotonia during growth: depending on the disease and natural history, the treatment may involve non-operative methods or growing rods, followed by spinal fusion. A multidisciplinary approach is always required. Finally, the survival gains achieved in recent years increasingly require attention to preparing for adult life, to orthopaedic problems requiring treatment before the patient leaves the paediatric environment, and to the transition towards the adult healthcare system. Copyright © 2017. Published by Elsevier Masson SAS.

After-effects of peripheral neurostimulation on brain plasticity and ankle function in chronic stroke: The role of afferents recruited.

PubMed

Beaulieu, Louis-David; Massé-Alarie, Hugo; Camiré-Bernier, Samuel; Ribot-Ciscar, Édith; Schneider, Cyril

2017-09-01

This study tested the after-effects of neuromuscular electrical stimulation (NMES), repetitive peripheral magnetic stimulation (rPMS) and muscle tendon vibration (VIB) on brain plasticity and sensorimotor impairments in chronic stroke to investigate whether different results could depend on the nature of afferents recruited by each technique. Fifteen people with chronic stroke participated in five sessions (one per week). Baseline measures were collected in session one, then, each participant received 4 randomly ordered interventions (NMES, rPMS, VIB and a 'control' intervention of exercises). Interventions were applied to the paretic ankle muscles and parameters of application were matched as closely as possible. Standardized clinical measures of the ankle function on the paretic side and transcranial magnetic stimulation (TMS) outcomes of both primary motor cortices (M1) were collected at pre- and post-application of each intervention. The ankle muscle strength was significantly improved by rPMS and VIB (P≤0.02). rPMS influenced M1 excitability (increase in the contralesional hemisphere, P=0.03) and inhibition (decrease in both hemispheres, P≤0.04). The group mean of a few clinical outcomes improved across sessions, i.e. independently of the order of interventions. Some TMS outcomes at baseline could predict the responsiveness to rPMS and VIB. This original study suggests that rPMS and VIB were efficient to drive M1 plasticity and sensorimotor improvements, likely via massive inflows of 'pure' proprioceptive information generated. Usefulness of some TMS outcomes to predict which intervention a patient could be more responsive to should be further tested in future studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Mechanical ventilation alone, and in the presence sepsis, induces peripheral skeletal muscle catabolism in neonatal pigs

USDA-ARS?s Scientific Manuscript database

Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle.

PubMed

Yim, Peter D; Gallos, George; Perez-Zoghbi, Jose F; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W

2013-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.

Perforator-based island flap with a peripheral muscle patch for coverage of sacral sores.

PubMed

Chang, Jung Woo; Lee, Jang Hyun; Choi, Matthew Seung Suk

2016-06-01

Despite numerous therapeutic advances, the treatment of pressure sores remains a challenge. The increased use of perforator flaps enables surgeons to minimize donor-site morbidity by sparing the underlying muscle. In the presence of focal deep spaces, however, the inclusion of muscle would be beneficial. The goal of this study was to introduce a method for including a muscle patch at the periphery of a perforator-based island flap for coverage of sacral pressure sores. Between March 2010 and February 2015, 26 patients with stage IV sacral sores underwent perforator-based island flap reconstruction with a peripheral muscle patch. Patient characteristics, including sex, age, defect size, and postoperative complications, were recorded. All flaps survived without major complications. No flap necrosis was noted. The present study shows that a muscle patch incorporated into the periphery of a perforator-based flap can be transferred safely. This can be a good surgical option in cases where infection control or more volume is needed. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

PubMed

Grassi, Bruno; Majerczak, Joanna; Bardi, Eleonora; Buso, Alessia; Comelli, Marina; Chlopicki, Stefan; Guzik, Magdalena; Mavelli, Irene; Nieckarz, Zenon; Salvadego, Desy; Tyrankiewicz, Urszula; Skórka, Tomasz; Bottinelli, Roberto; Zoladz, Jerzy A; Pellegrino, Maria Antonietta

2017-08-01

Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα q *44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgα q *44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgα q *44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance. NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed in transgenic chronic heart failure mice, evaluated in the critical period between the occurrence of an impairment of cardiac function and the terminal stage of the disease. Exercise training improved exercise performance and cardiac function, but it did not affect the impaired mitochondrial respiration. Factors "upstream" of mitochondria, including an enhanced cardiovascular O 2 delivery, were mainly responsible for the functional improvement. Copyright © 2017 the American Physiological Society.

Induction of cortical plasticity for reciprocal muscles by paired associative stimulation

PubMed Central

Suzuki, Makoto; Kirimoto, Hikari; Sugawara, Kazuhiro; Watanabe, Makoto; Shimizu, Shinobu; Ishizaka, Ikuyo; Yamada, Sumio; Matsunaga, Atsuhiko; Fukuda, Michinari; Onishi, Hideaki

2014-01-01

Background Paired associative stimulation (PAS) is widely used to induce plasticity in the human motor cortex. Although reciprocal inhibition of antagonist muscles plays a fundamental role in human movements, change in cortical circuits for reciprocal muscles by PAS is unknown. Methods We investigated change in cortical plasticity for reciprocal muscles during PAS. PAS consisted of 200 pairs of peripheral electric stimulation of the right median nerve at the wrist at a frequency of 0.25 Hz followed by transcranial magnetic stimulation of the left M1 at the midpoint between the center of gravities of the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles. Measures of motor cortical excitability included resting motor threshold (RMT), GABAA-mediated short-interval intracortical inhibition (SICI), and GABAB-mediated long-interval intracortical inhibition (LICI). Results Motor evoked potential amplitude-conditioned LICI for the FCR muscle was significantly decreased after PAS (P = 0.020), whereas that for the ECR muscle was significantly increased (P = 0.033). Changes in RMT and SICI for the FCR and ECR muscles were not significantly different before and after PAS. Corticospinal excitability for both reciprocal muscles was increased during PAS, but GABAB-mediated cortical inhibitory functions for the agonist and antagonist muscles were reciprocally altered after PAS. Conclusion These results implied that the cortical excitability for reciprocal muscles including GABAB-ergic inhibitory systems within human M1 could be differently altered by PAS. PMID:25365805

Presynaptic NCAM Is Required for Motor Neurons to Functionally Expand Their Peripheral Field of Innervation in Partially Denervated Muscles

PubMed Central

Chipman, Peter H.; Schachner, Melitta

2014-01-01

The function of neural cell adhesion molecule (NCAM) expression in motor neurons during axonal sprouting and compensatory reinnervation was explored by partially denervating soleus muscles in mice lacking presynaptic NCAM (Hb9creNCAMflx). In agreement with previous studies, the contractile force of muscles in wild-type (NCAM+/+) mice recovered completely 2 weeks after 75% of the motor innervation was removed because motor unit size increased by 2.5 times. In contrast, similarly denervated muscles in Hb9creNCAMflx mice failed to recover the force lost due to the partial denervation because motor unit size did not change. Anatomical analysis indicated that 50% of soleus end plates were completely denervated 1–4 weeks post-partial denervation in Hb9creNCAMflx mice, while another 25% were partially reinnervated. Synaptic vesicles (SVs) remained at extrasynaptic regions in Hb9creNCAMflx mice rather than being distributed, as occurs normally, to newly reinnervated neuromuscular junctions (NMJs). Electrophysiological analysis revealed two populations of NMJs in partially denervated Hb9creNCAMflx soleus muscles, one with high (mature) quantal content, and another with low (immature) quantal content. Extrasynaptic SVs in Hb9creNCAMflx sprouts were associated with L-type voltage-dependent calcium channel (L-VDCC) immunoreactivity and maintained an immature, L-VDCC-dependent recycling phenotype. Moreover, acute nifedipine treatment potentiated neurotransmission at newly sprouted NMJs, while chronic intraperitoneal treatment with nifedipine during a period of synaptic consolidation enhanced functional motor unit expansion in the absence of presynaptic NCAM. We propose that presynaptic NCAM bridges a critical link between the SV cycle and the functional expansion of synaptic territory through the regulation of L-VDCCs. PMID:25100585

The quest for the bionic arm.

PubMed

Hutchinson, Douglas T

2014-06-01

The current state of research of upper extremity prosthetic devices is focused on creating a complete prosthesis with full motor and sensory function that will provide amputees with a near-normal human arm. Although advances are being made rapidly, many hurdles remain to be overcome before a functional, so-called bionic arm is a reality. Acquiring signals via nerve or muscle inputs will require either a reliable wireless device or direct wiring through an osseous-integrated implant. The best way to tap into the "knowledge" present in the peripheral nerve is yet to be determined. Copyright 2014 by the American Academy of Orthopaedic Surgeons.

Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

PubMed

Bauché, Stéphanie; Boerio, Delphine; Davoine, Claire-Sophie; Bernard, Véronique; Stum, Morgane; Bureau, Cécile; Fardeau, Michel; Romero, Norma Beatriz; Fontaine, Bertrand; Koenig, Jeanine; Hantaï, Daniel; Gueguen, Antoine; Fournier, Emmanuel; Eymard, Bruno; Nicole, Sophie

2013-12-01

Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Low anaerobic threshold and increased skeletal muscle lactate production in subjects with Huntington's disease.

PubMed

Ciammola, Andrea; Sassone, Jenny; Sciacco, Monica; Mencacci, Niccolò E; Ripolone, Michela; Bizzi, Caterina; Colciago, Clarissa; Moggio, Maurizio; Parati, Gianfranco; Silani, Vincenzo; Malfatto, Gabriella

2011-01-01

Mitochondrial defects that affect cellular energy metabolism have long been implicated in the etiology of Huntington's disease (HD). Indeed, several studies have found defects in the mitochondrial functions of the central nervous system and peripheral tissues of HD patients. In this study, we investigated the in vivo oxidative metabolism of exercising muscle in HD patients. Ventilatory and cardiometabolic parameters and plasma lactate concentrations were monitored during incremental cardiopulmonary exercise in twenty-five HD subjects and twenty-five healthy subjects. The total exercise capacity was normal in HD subjects but notably the HD patients and presymptomatic mutation carriers had a lower anaerobic threshold than the control subjects. The low anaerobic threshold of HD patients was associated with an increase in the concentration of plasma lactate. We also analyzed in vitro muscular cell cultures and found that HD cells produce more lactate than the cells of healthy subjects. Finally, we analyzed skeletal muscle samples by electron microscopy and we observed striking mitochondrial structural abnormalities in two out of seven HD subjects. Our findings confirm mitochondrial abnormalities in HD patients' skeletal muscle and suggest that the mitochondrial dysfunction is reflected functionally in a low anaerobic threshold and an increased lactate synthesis during intense physical exercise. Copyright © 2010 Movement Disorder Society.

Somatosensory Neurotoxicity: Agents and Assessment Methodology.

EPA Science Inventory

The somatosensory system is comprised of a variety of sensory receptors located in the skin, muscle tendons, and visceral organs that are innervated by myelinated and nonmyelinated axons of the peripheral nervous system. These peripheral sensory nerve fibers in tum communicate so...

Somatosensory Neurotoxicity: Agents and Assessment Methodology

EPA Science Inventory

The somatosensory system is comprised of a variety of sensory receptors located in the skin, muscle tendons, and visceral organs that are innervated by myelinated and nonmyelinated axons of the peripheral nervous system. These peripheral sensory nerve fibers in turn communicate s...

Changes in body temperature in king penguins at sea: the result of fine adjustments in peripheral heat loss?

PubMed

Schmidt, Alexander; Alard, Frank; Handrich, Yves

2006-09-01

To investigate thermoregulatory adjustments at sea, body temperatures (the pectoral muscle and the brood patch) and diving behavior were monitored during a foraging trip of several days at sea in six breeding king penguins Aptenodytes patagonicus. During inactive phases at sea (water temperature: 4-7 degrees C), all tissues measured were maintained at normothermic temperatures. The brood patch temperature was maintained at the same values as those measured when brooding on shore (38 degrees C). This high temperature difference causes a significant loss of heat. We hypothesize that high-energy expenditure associated with elevated peripheral temperature when resting at sea is the thermoregulatory cost that a postabsorptive penguin has to face for the restoration of its subcutaneous body fat. During diving, mean pectoral temperature was 37.6 +/- 1.6 degrees C. While being almost normothermic on average, the temperature of the pectoral muscle was still significantly lower than during inactivity in five out of the six birds and underwent temperature drops of up to 5.5 degrees C. Mean brood patch temperature was 29.6 +/- 2.5 degrees C during diving, and temperature decreases of up to 21.6 degrees C were recorded. Interestingly, we observed episodes of brood patch warming during the descent to depth, suggesting that, in some cases, king penguins may perform active thermolysis using the brood patch. It is hypothesized that functional pectoral temperature may be regulated through peripheral adjustments in blood perfusion. These two paradoxical features, i.e., lower temperature of deep tissues during activity and normothermic peripheral tissues while inactive, may highlight the key to the energetics of this diving endotherm while foraging at sea.

Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of Bathyergidae.

PubMed

St John Smith, Ewan; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

2012-08-15

In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. Copyright © 2012 Wiley Periodicals, Inc.

Specific Paucity of Unmyelinated C-Fibers in Cutaneous Peripheral Nerves of the African Naked-Mole Rat: Comparative Analysis Using Six Species of Bathyergidae

PubMed Central

Smith, Ewan S; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

2012-01-01

In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. J. Comp. Neurol. 520:2785–2803, 2012. © 2012 Wiley Periodicals, Inc. PMID:22528859

Exercise-mimetic AICAR transiently benefits brain function

PubMed Central

Guerrieri, Davide; van Praag, Henriette

2015-01-01

Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP-kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function. PMID:26286955

Exercise-mimetic AICAR transiently benefits brain function.

PubMed

Guerrieri, Davide; van Praag, Henriette

2015-07-30

Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP-kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function.

Pathogenesis of the limb manifestations and exercise limitations in peripheral artery disease.

PubMed

Hiatt, William R; Armstrong, Ehrin J; Larson, Christopher J; Brass, Eric P

2015-04-24

Patients with peripheral artery disease have a marked reduction in exercise performance and daily ambulatory activity irrespective of their limb symptoms of classic or atypical claudication. This review will evaluate the multiple pathophysiologic mechanisms underlying the exercise impairment in peripheral artery disease based on an evaluation of the current literature and research performed by the authors. Peripheral artery disease results in atherosclerotic obstructions in the major conduit arteries supplying the lower extremities. This arterial disease process impairs the supply of oxygen and metabolic substrates needed to match the metabolic demand generated by active skeletal muscle during walking exercise. However, the hemodynamic impairment associated with the occlusive disease process does not fully account for the reduced exercise impairment, indicating that additional pathophysiologic mechanisms contribute to the limb manifestations. These mechanisms include a cascade of pathophysiological responses during exercise-induced ischemia and reperfusion at rest that are associated with endothelial dysfunction, oxidant stress, inflammation, and muscle metabolic abnormalities that provide opportunities for targeted therapeutic interventions to address the complex pathophysiology of the exercise impairment in peripheral artery disease. © 2015 American Heart Association, Inc.

Deficiency in Monocarboxylate Transporter 1 (MCT1) in Mice Delays Regeneration of Peripheral Nerves following Sciatic Nerve Crush

PubMed Central

Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothstein, Jeffrey D.

2014-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence and MCT1 tdTomato BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves in MCT1 heterozygous null mice are crushed and peripheral nerve regeneration quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly through failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. PMID:25447940

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush.

PubMed

Morrison, Brett M; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H; Lengacher, Sylvain; Magistretti, Pierre J; Pellerin, Luc; Rothstein, Jeffrey D

2015-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous null mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. Copyright © 2014 Elsevier Inc. All rights reserved.

Intravenous immunoglobulin for chronic residual peripheral neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a multicenter, double-blind trial.

PubMed

Koike, Haruki; Akiyama, Kazuo; Saito, Toyokazu; Sobue, Gen

2015-03-01

Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome, frequently affects the peripheral nervous system. We conducted a multicenter, double-blind, three-arm treatment period, randomized, pre-post trial to assess the efficacy of intravenous immunoglobulin (IVIg) administration for residual peripheral neuropathy in patients with EGPA that is in remission, indicated by laboratory indices. Twenty-three patients were randomly assigned into three groups, in which the timing of IVIg and placebo administration was different. Each group received one course of intervention and two courses of placebo at 2-week intervals. Treatment effects were assessed every 2 weeks for 8 weeks. The primary outcome measure, the amount of change in the manual muscle testing sum score 2 weeks after IVIg administration, significantly increased (p = 0.002). The results over time suggested that this effect continued until the last assessment was done 8 weeks later. The number of muscles with manual muscle testing scores of three or less (p = 0.004) and the neuropathic pain scores represented by the visual analogue scale (p = 0.005) also improved significantly 2 weeks after IVIg administration. This study indicates that IVIg treatment for EGPA patients with residual peripheral neuropathy should be considered even when laboratory indices suggest remission of the disease.

GLUT-3 expression in human skeletal muscle

NASA Technical Reports Server (NTRS)

Stuart, C. A.; Wen, G.; Peng, B. H.; Popov, V. L.; Hudnall, S. D.; Campbell, G. A.

2000-01-01

Muscle biopsy homogenates contain GLUT-3 mRNA and protein. Before these studies, it was unclear where GLUT-3 was located in muscle tissue. In situ hybridization using a midmolecule probe demonstrated GLUT-3 within all muscle fibers. Fluorescent-tagged antibody reacting with affinity-purified antibody directed at the carboxy-terminus demonstrated GLUT-3 protein in all fibers. Slow-twitch muscle fibers, identified by NADH-tetrazolium reductase staining, possessed more GLUT-3 protein than fast-twitch fibers. Electron microscopy using affinity-purified primary antibody and gold particle-tagged second antibody showed that the majority of GLUT-3 was in association with triads and transverse tubules inside the fiber. Strong GLUT-3 signals were seen in association with the few nerves that traversed muscle sections. Electron microscopic evaluation of human peripheral nerve demonstrated GLUT-3 within the axon, with many of the particles related to mitochondria. GLUT-3 protein was found in myelin but not in Schwann cells. GLUT-1 protein was not present in nerve cells, axons, myelin, or Schwann cells but was seen at the surface of the peripheral nerve in the perineurium. These studies demonstrated that GLUT-3 mRNA and protein are expressed throughout normal human skeletal muscle, but the protein is predominantly found in the triads of slow-twitch muscle fibers.

[Peripheral facial paralysis: the role of physical medicine and rehabilitation].

PubMed

Matos, Catarina

2011-12-01

Peripheral facial paralysis (PFP) is a consequence of the peripheral neuronal lesion of the facial nerve (FN). It can be either primary (Bell`s Palsy) or secondary. The classical clinical presentation typically involves both stages of the hemiface. However, there may be other symptoms (ex. xerophthalmia, hyperacusis, phonation and deglutition changes) that one should recall. Clinical evaluation includes rigorous muscle tonus and sensibility search in the FN territory. Some useful instruments allow better objectivity in the patients' evaluation (House-Brackmann System, Facial Grading System, Functional Evaluation). There are clear referral criteria to Physical Medicine and Rehabilitation. Treatment of Bell`s Palsy may include pharmacotherapy, neuromuscular training (NMT), physical methods and surgery. In the NMT field the several treatment techniques are systematized. Therapeutic strategies should be problem-oriented and adjusted to the patient's symptoms and signs. Physical methods are reviewed. In about 15-20 % of patients permanent sequelae subside after 3 months of evolution. PFP is commonly a multidisciplinary condition. Therefore, it is important to review strategies that Physical Medicine and Rehabilitation may offer.

Upper and lower limb muscles in patients with COPD: similarities in muscle efficiency but differences in fatigue resistance.

PubMed

Miranda, Eduardo Foschini; Malaguti, Carla; Marchetti, Paulo Henrique; Dal Corso, Simone

2014-01-01

Peripheral muscle dysfunction is a common finding in patients with COPD; however, the structural adaptation and functional impairment of the upper and lower limb muscles do not seem to be homogenous. We compared muscle fatigue and recovery time between 2 representative muscles: the middle deltoid and the quadriceps femoris. Twenty-one subjects with COPD (FEV1 46.1 ± 10.3% of predicted) underwent maximal voluntary isometric contraction and an endurance test (60% of maximal voluntary isometric contraction, to the limit of tolerance). The maximal voluntary isometric contraction test was repeated after 10 min, 30 min, 60 min, and 24 hours for both the quadriceps femoris and middle deltoid. Surface electromyography was recorded throughout the endurance test. Maximal voluntary isometric contraction significantly decreased only for the middle deltoid between 10 and 60 min after the endurance test. A significant increase of the root mean square and a greater decline in median frequency throughout the endurance test occurred for the middle deltoid, compared with the quadriceps femoris. When dyspnea and fatigue scores were corrected by endurance time, higher values were observed for the middle deltoid (0.07 and 0.08, respectively) in relation to the quadriceps femoris (0.02 and 0.03, respectively). Subjects with COPD had a higher fatigability of a representative upper limb muscle (middle deltoid) than a lower limb muscle (quadriceps femoris).

Stereotypic Laryngeal and Respiratory Motor Patterns Generate Different Call Types in Rat Ultrasound Vocalization

PubMed Central

RIEDE, TOBIAS

2014-01-01

Rodents produce highly variable ultrasound whistles as communication signals unlike many other mammals, who employ flow-induced vocal fold oscillations to produce sound. The role of larynx muscles in controlling sound features across different call types in ultrasound vocalization (USV) was investigated using laryngeal muscle electromyographic (EMG) activity, subglottal pressure measurements and vocal sound output in awake and spontaneously behaving Sprague–Dawley rats. Results support the hypothesis that glottal shape determines fundamental frequency. EMG activities of thyroarytenoid and cricothyroid muscles were aligned with call duration. EMG intensity increased with fundamental frequency. Phasic activities of both muscles were aligned with fast changing fundamental frequency contours, for example in trills. Activities of the sternothyroid and sternohyoid muscles, two muscles involved in vocal production in other mammals, are not critical for the production of rat USV. To test how stereotypic laryngeal and respiratory activity are across call types and individuals, sets of ten EMG and subglottal pressure parameters were measured in six different call types from six rats. Using discriminant function analysis, on average 80% of parameter sets were correctly assigned to their respective call type. This was significantly higher than the chance level. Since fundamental frequency features of USV are tightly associated with stereotypic activity of intrinsic laryngeal muscles and muscles contributing to build-up of subglottal pressure, USV provide insight into the neurophysiological control of peripheral vocal motor patterns. PMID:23423862

The Nitrate-nitrite-NO pathway and its implications for Heart Failure and Preserved Ejection Fraction

PubMed Central

Chirinos, Julio A.; Zamani, Payman

2016-01-01

The pathogenesis of exercise intolerance in patients with heart failure and preserved ejection fraction (HFpEF) is likely multifactorial. In addition to cardiac abnormalities (diastolic dysfunction, abnormal contractile reserve, chronotropic incompetence), several peripheral abnormalities are likely to be involved. These include abnormal pulsatile hemodynamics, abnormal arterial vasodilatory responses to exercise, and abnormal peripheral O2 delivery, extraction and utilization. The nitrate-nitrite-NO pathway is emerging as a potential target to modify key physiologic abnormalities, including late systolic LV load from arterial wave reflections (which has deleterious short- and long-term consequences for the LV), arterial vasodilatory reserve, muscle O2 delivery, and skeletal muscle mitochondrial function. In a recently completed randomized trial, the administration of a single dose of exogenous inorganic nitrate has been shown exert various salutary arterial hemodynamic effects, ultimately leading to enhanced aerobic capacity in patients with HFpEF. These effects have the potential for both immediate improvements in exercise tolerance and for long-term “disease-modifying” effects. In this review, we provide an overview of key mechanistic contributors to exercise intolerance in HFpEF, and of the potential therapeutic role of drugs that target the nitrate-nitrite-NO pathway. PMID:26792295

Lack of Neuropathy-Related Phenotypes in Hint1 Knockout Mice

PubMed Central

Seburn, Kevin L.; Morelli, Kathryn H.; Jordanova, Albena; Burgess, Robert W.

2014-01-01

Mutations in HINT1, the gene encoding histidine triad nucleotide-binding protein 1 (HINT1), cause a recessively inherited peripheral neuropathy that involves primarily motor dysfunction and is usually associated with neuromyotonia, i.e. prolonged muscle contraction resulting from hyperexcitability of the peripheral nerve. Because these mutations are hypothesized to cause loss of function, we analyzed Hint1 knockout mice for their relevance as a disease model. Mice lacking Hint1 were normal in appearance and in behavioral tests or motor performance, although they moved slower and for a smaller fraction of time than wild-type (WT) mice in an open field arena. Muscles, neuromuscular junctions, and nodes of Ranvier are anatomically normal and did not show evidence of degeneration or regeneration. Axon numbers and myelination in peripheral nerves were normal at 4 and 13 months of age. Axons were slightly smaller than those in WT mice at 4 months of age, but this did not cause a decrease in conduction velocity, and no differences in axon diameters were detected at 13 months. Using electromyography, we were unable to detect neuromyotonia, even using supra-physiological stimuli and stressors such as reduced temperature or 3,4 diaminopyridine to block potassium channels. Therefore, we conclude that Hint1 knockout mice may be useful for studying the biochemical activities of HINT1, but these mice do not provide a disease model or a means for investigating the basis of HINT1-associated neuropathy and neuromyotonia. PMID:24918641

Peripheral muscle composition and health status in patients with COPD.

PubMed

Montes de Oca, María; Torres, Sonia H; Gonzalez, Yudith; Romero, Elizabeth; Hernández, Noelina; Mata, Abdón; Tálamo, Carlos

2006-10-01

The present study evaluated the relationship between health status (HS) and peripheral muscle histochemical characteristics in chronic obstructive pulmonary disease (COPD), and identified selected independent respiratory and extrapulmonary variables that predicted the HS of these patients. Cross-sectional study. Outpatient respiratory clinic of a university hospital. We studied 29 patients (63+/-10 yrs) with a forced expiratory volume in 1s (FEV1) of 39+/-12%. All patients underwent vastus lateralis muscle biopsies for histochemical analysis. They also had spirometry, arterial blood gas analysis, body mass index (BMI), dyspnea determined with the MMRC scale and responded to the St. George's Respiratory Questionnaire (SGRQ) for HS assessment. SGRQ total score correlated with fiber type distribution. A stepwise multiple regression identified three independent predictors of SGRQ total score: type I fiber proportion, BMI, and FEV1; r = 0.78 and r2 = 0.61. These results indicate that impaired HS in COPD is related to the peripheral muscle changes characterized by less type I fibers proportion. The findings argue in favor of an important contribution of the systemic consequences on the HS in COPD independently from the airflow limitation severity, and help to explain the observation of the poor correlation between the degree of airflow limitation and SGRQ total score.

Development of a Regenerative Peripheral Nerve Interface for Control of a Neuroprosthetic Limb

PubMed Central

Frost, Christopher M.; Martin, David C.; Larkin, Lisa M.

2016-01-01

Background. The purpose of this experiment was to develop a peripheral nerve interface using cultured myoblasts within a scaffold to provide a biologically stable interface while providing signal amplification for neuroprosthetic control and preventing neuroma formation. Methods. A Regenerative Peripheral Nerve Interface (RPNI) composed of a scaffold and cultured myoblasts was implanted on the end of a divided peroneal nerve in rats (n = 25). The scaffold material consisted of either silicone mesh, acellular muscle, or acellular muscle with chemically polymerized poly(3,4-ethylenedioxythiophene) conductive polymer. Average implantation time was 93 days. Electrophysiological tests were performed at endpoint to determine RPNI viability and ability to transduce neural signals. Tissue samples were examined using both light microscopy and immunohistochemistry. Results. All implanted RPNIs, regardless of scaffold type, remained viable and displayed robust vascularity. Electromyographic activity and stimulated compound muscle action potentials were successfully recorded from all RPNIs. Physiologic efferent motor action potentials were detected from RPNIs in response to sensory foot stimulation. Histology and transmission electron microscopy revealed mature muscle fibers, axonal regeneration without neuroma formation, neovascularization, and synaptogenesis. Desmin staining confirmed the preservation and maturation of myoblasts within the RPNIs. Conclusions. RPNI demonstrates significant myoblast maturation, innervation, and vascularization without neuroma formation. PMID:27294122

Fluctuations in central and peripheral temperatures induced by intravenous nicotine: central and peripheral contributions

PubMed Central

Tang, Jeremy; Kiyatkin, Eugene A.

2011-01-01

Nicotine (NIC) is a highly addictive substance that interacts with different subtypes of nicotinic acetylcholine receptors widely distributed in the central and peripheral nervous systems. While the direct action of NIC on central neurons appears to be essential for its reinforcing properties, the role of peripheral actions of this drug remains a matter of controversy. In this study, we examined changes in locomotor activity and temperature fluctuations in the brain (nucleus accumbens and ventral tegmental area), temporal muscle, and skin induced by intravenous (iv) NIC at low human-relevant doses (10 and 30 μg/kg) in freely moving rats. These effects were compared to those induced by social interaction, an arousing procedure that induces behavioral activation and temperature responses via pure neural mechanism procedure, and iv injections of a peripherally acting NIC analogue, NIC pyrrolidine methiodide (NIC-PM) used at equimolar doses. We found that NIC at 30 μg/kg induces a modest locomotor activation, rapid and strong decrease in skin temperature, and weak increases in brain and muscle temperature. While these effects were qualitatively similar to those induced by social interaction, they were much weaker and showed a tendency to increase with repeated drug administrations. In contrast, NIC-PM did not affect locomotion and induced much weaker than NIC increases in brain and muscle temperatures and decreases in skin temperature; these effects showed a tendency to be weaker with repeated drug administrations. Our data indicate that NIC's actions in the brain are essential to induce locomotor activation and brain and body hyperthermic responses. However, rapid peripheral action of NIC on sensory afferents could be an important factor in triggering its central effects, contributing to neural and physiological activation following repeated drug use. PMID:21295014

Mitochondrial Respiration after One Session of Calf Raise Exercise in Patients with Peripheral Vascular Disease and Healthy Older Adults.

PubMed

van Schaardenburgh, Michel; Wohlwend, Martin; Rognmo, Øivind; Mattsson, Erney J R

2016-01-01

Mitochondria are essential for energy production in the muscle cell and for this they are dependent upon a sufficient supply of oxygen by the circulation. Exercise training has shown to be a potent stimulus for physiological adaptations and mitochondria play a central role. Whether changes in mitochondrial respiration are seen after exercise in patients with a reduced circulation is unknown. The aim of the study was to evaluate the time course and whether one session of calf raise exercise stimulates mitochondrial respiration in the calf muscle of patients with peripheral vascular disease. One group of patients with peripheral vascular disease (n = 11) and one group of healthy older adults (n = 11) were included. Patients performed one session of continuous calf raises followed by 5 extra repetitions after initiation of pain. Healthy older adults performed 100 continuous calf raises. Gastrocnemius muscle biopsies were collected at baseline and 15 minutes, one hour, three hours and 24 hours after one session of calf raise exercise. A multi substrate (octanoylcarnitine, malate, adp, glutamate, succinate, FCCP, rotenone) approach was used to analyze mitochondrial respiration in permeabilized fibers. Mixed-linear model for repeated measures was used for statistical analyses. Patients with peripheral vascular disease have a lower baseline respiration supported by complex I and they increase respiration supported by complex II at one hour post-exercise. Healthy older adults increase respiration supported by electron transfer flavoprotein and complex I at one hour and 24 hours post-exercise. Our results indicate a shift towards mitochondrial respiration supported by complex II as being a pathophysiological component of peripheral vascular disease. Furthermore exercise stimulates mitochondrial respiration already after one session of calf raise exercise in patients with peripheral vascular disease and healthy older adults. ClinicalTrials.gov NCT01842412.

BDNF gene delivery mediated by neuron-targeted nanoparticles is neuroprotective in peripheral nerve injury.

PubMed

Lopes, Cátia D F; Gonçalves, Nádia P; Gomes, Carla P; Saraiva, Maria J; Pêgo, Ana P

2017-03-01

Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model. The TMCSH-HC/BDNF nanoparticle treatment promoted the release and significant expression of BDNF in neural tissues, which resulted in an enhanced functional recovery after injury as compared to control treatments (vehicle and non-targeted nanoparticles), associated with an improvement in key pro-regenerative events, namely, the increased expression of neurofilament and growth-associated protein GAP-43 in the injured nerves. Moreover, the targeted nanoparticle treatment was correlated with a significantly higher density of myelinated axons in the distal stump of injured nerves, as well as with preservation of unmyelinated axon density as compared with controls and a protective role in injury-denervated muscles, preventing them from denervation. These results highlight the potential of TMCSH-HC nanoparticles as non-viral gene carriers to deliver therapeutic genes into the peripheral neurons and thus, pave the way for their use as an effective therapeutic intervention for peripheral neuropathies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque

NASA Astrophysics Data System (ADS)

Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Tat, D. M.; Bullard, A. J.; Woo, S. L.; Sando, I. C.; Urbanchek, M. G.; Cederna, P. S.; Chestek, C. A.

2016-08-01

Objective. Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. Approach. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. Main results. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey’s finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. Significance. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque.

PubMed

Irwin, Z T; Schroeder, K E; Vu, P P; Tat, D M; Bullard, A J; Woo, S L; Sando, I C; Urbanchek, M G; Cederna, P S; Chestek, C A

2016-08-01

Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey's finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

An in vivo study of tricalcium phosphate and glutaraldehyde crosslinking gelatin conduits in peripheral nerve repair.

PubMed

Chen, Ming-Hong; Chen, Pei-Ru; Chen, Mei-Hsiu; Hsieh, Sung-Tsang; Huang, Jing-Shan; Lin, Feng-Huei

2006-04-01

In order to modulate the mechanical properties of gelatin, we previously developed a biodegradable composite composed by tricalcium phosphate and glutaraldehyde crosslinking gelatin (GTG) feasible for surgical manipulation. In this study, we evaluated the in vivo applications of GTG conduit for peripheral nerve repair. The effect of sciatic nerve reconstruction was compared between resorbable permeable GTG conduits and durable impermeable silicone tubes. Traditional methods of assessing nerve recovery following peripheral nerve repair including histomorphometric and electrophysiologic features were conducted in our study. In addition, autotomy score and sciatic function index (SFI) in walking tract analysis were used as additional parameters for assessing the return of nerve function. Twenty-four weeks after sciatic nerve repair, the GTG conduits were harvested. Microscopically, regeneration of nerves was observed in the cross-section at the mid portion of all implanted GTG conduits. The cross-sectional area of regenerated nerve of the GTG group was significant larger than that of the silicone group. In the compound muscle action potentials (CMAP), the mean recovery index of CMAP amplitude was 0.24 +/- 0.02 for the silicone group, 0.41 +/- 0.07 for the GTG group. The mean SFI increased with time in the GTG group during the evaluation period until 24 weeks. Walking tract analysis showed a higher SFI score in the GTG group at both 12 and 24 weeks. The difference reached a significant level at 24 weeks. Thus, the histomorphometric, electrophysiologic, and functional assessments demonstrate that GTG can be a candidate for peripheral nerve repair.

Tesamorelin Therapy to Enhance Axonal Regeneration, Minimize Muscle Atrophy and Improve Functional Outcomes Following Peripheral Nerve Injury and Repair

DTIC Science & Technology

2017-10-01

Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT We are currently completing the set-up phase for this study . We have hired and trained all...Hospital and University of Maryland Medical Center/Shock Trauma). The final step with regards to study set up prior to beginning recruitment will be...to receive HRPO approval. 15. SUBJECT TERMS IRB, FDA IND exemption, HRPO, study set-up phase 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

The role of precisely matching fascicles in the quick recovery of nerve function in long peripheral nerve defects

PubMed Central

Yan, Liwei; Yao, Zhi; Lin, Tao; Zhu, Qingtang; Qi, Jian; Gu, Liqiang; Fang, Jintao; Zhou, Xiang

2017-01-01

Peripheral nerve injury therapy in the clinic remains less than satisfactory. The gold standard of treatment for long peripheral nerve defects is autologous nerve grafts; however, numerous clinical complications are associated with this treatment. As tissue engineering has developed, tissue-engineered nerve grafts (TENGs) have shown potential applications as alternatives to autologous nerve grafts. To verify the important role of the biomimetic pathway of fascicle design in TENGs, we designed an animal model to study the role of the precise matching of fascicles in the effectiveness of nerve function recovery. 24 Sprague-Dawley rats were divided randomly into three groups (eight/group) that corresponded to 100% fascicle matching (100%FM), 50%FM and 0%FM. We selected Sprague–Dawley rat long-gap (15 mm) sciatic nerve defects. In the 6 weeks after surgery, we found that the 100%FM group showed the most effective functional recovery among the three groups. The 100%FM group showed better functional recovery on the basis of the sciatic functional index than the 50%FM and 0%FM groups. According to histological evaluation, the 100%FM group showed more regenerating nerve fibres. Moreover, in terms of the prevention of muscle atrophy, the 100%FM group showed excellent physiological outcomes. The 100%FM as tissue-engineered scaffolds can enhance nerve regeneration and effective functional recovery after the repair of large nerve defects. The results of this study provide a theoretical basis for future TENG designs including biomimetic fascicle pathways for repairing long nerve defects. PMID:28914740

Exercise intolerance in Type 2 diabetes: is there a cardiovascular contribution?

PubMed

Poitras, Veronica J; Hudson, Robert W; Tschakovsky, Michael E

2018-05-01

Physical activity is critically important for Type 2 diabetes management, yet adherence levels are poor. This might be partly due to disproportionate exercise intolerance. Submaximal exercise tolerance is highly sensitive to muscle oxygenation; impairments in exercising muscle oxygen delivery may contribute to exercise intolerance in Type 2 diabetes since there is considerable evidence for the existence of both cardiac and peripheral vascular dysfunction. While uncompromised cardiac output during submaximal exercise is consistently observed in Type 2 diabetes, it remains to be determined whether an elevated cardiac sympathetic afferent reflex could sympathetically restrain exercising muscle blood flow. Furthermore, while deficits in endothelial function are common in Type 2 diabetes and are often cited as impairing exercising muscle oxygen delivery, no direct evidence in exercise exists, and there are several other vasoregulatory mechanisms whose dysfunction could contribute. Finally, while there are findings of impaired oxygen delivery, conflicting evidence also exists. A definitive conclusion that Type 2 diabetes compromises exercising muscle oxygen delivery remains premature. We review these potentially dysfunctional mechanisms in terms of how they could impair oxygen delivery in exercise, evaluate the current literature on whether an oxygen delivery deficit is actually manifest, and correspondingly identify key directions for future research.

Human alcohol-related neuropathology

PubMed Central

Kril, Jillian J.

2015-01-01

Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions. PMID:24370929

Resistance Training using Low Cost Elastic Tubing is Equally Effective to Conventional Weight Machines in Middle-Aged to Older Healthy Adults: A Quasi-Randomized Controlled Clinical Trial.

PubMed

Lima, Fabiano F; Camillo, Carlos A; Gobbo, Luis A; Trevisan, Iara B; Nascimento, Wesley B B M; Silva, Bruna S A; Lima, Manoel C S; Ramos, Dionei; Ramos, Ercy M C

2018-03-01

The objectives of the study were to compare the effects of resistance training using either a low cost and portable elastic tubing or conventional weight machines on muscle force, functional exercise capacity, and health-related quality of life (HRQOL) in middle-aged to older healthy adults. In this clinical trial twenty-nine middle-aged to older healthy adults were randomly assigned to one of the three groups a priori defined: resistance training with elastic tubing (ETG; n = 10), conventional resistance training (weight machines) (CTG; n = 9) and control group (CG, n = 10). Both ETG and CTG followed a 12-week resistance training (3x/week - upper and lower limbs). Muscle force, functional exercise capacity and HRQOL were evaluated at baseline, 6 and 12 weeks. CG underwent the three evaluations with no formal intervention or activity counseling provided. ETG and CTG increased similarly and significantly muscle force (Δ16-44% in ETG and Δ25-46% in CTG, p < 0.05 for both), functional exercise capacity (ETG Δ4 ± 4% and CTG Δ6±8%; p < 0.05 for both). Improvement on "pain" domain of HRQOL could only be observed in the CTG (Δ21 ± 26% p = 0.037). CG showed no statistical improvement in any of the variables investigated. Resistance training using elastic tubing (a low cost and portable tool) and conventional resistance training using weight machines promoted similar positive effects on peripheral muscle force and functional exercise capacity in middle-aged to older healthy adults.

Valsalva's maneuver revisited: a quantitative method yielding insights into human autonomic control

NASA Technical Reports Server (NTRS)

Smith, M. L.; Beightol, L. A.; Fritsch-Yelle, J. M.; Ellenbogen, K. A.; Porter, T. R.; Eckberg, D. L.

1996-01-01

Seventeen healthy supine subjects performed graded Valsalva maneuvers. In four subjects, transesophageal echographic aortic cross-sectional areas decreased during and increased after straining. During the first seconds of straining, when aortic cross-sectional area was declining and peripheral arterial pressure was rising, peroneal sympathetic muscle neurons were nearly silent. Then, as aortic cross-sectional area and peripheral pressure both declined, sympathetic muscle nerve activity increased, in proportion to the intensity of straining. Poststraining arterial pressure elevations were proportional to preceding increases of sympathetic activity. Sympathetic inhibition after straining persisted much longer than arterial and right atrial pressure elevations. Similarly, R-R intervals changed in parallel with peripheral arterial pressure, until approximately 45 s after the onset of straining, when R-R intervals were greater and arterial pressures were smaller than prestraining levels. Our conclusions are as follows: opposing changes of carotid and aortic baroreceptor inputs reduce sympathetic muscle and increase vagal cardiac motor neuronal firing; parallel changes of barorsensory inputs provoke reciprocal changes of sympathetic and direct changes of vagal firing; and pressure transients lasting only seconds reset arterial pressure-sympathetic and -vagal response relations.

Differential involvement of forearm muscles in ALS does not relate to sonographic structural nerve alterations.

PubMed

Schreiber, Stefanie; Schreiber, Frank; Debska-Vielhaber, Grazyna; Garz, Cornelia; Hensiek, Nathalie; Machts, Judith; Abdulla, Susanne; Dengler, Reinhard; Petri, Susanne; Nestor, Peter J; Vielhaber, Stefan

2018-07-01

We aimed to assess whether differential peripheral nerve involvement parallels dissociated forearm muscle weakness in amyotrophic lateral sclerosis (ALS). The analysis comprised 41 ALS patients and 18 age-, sex-, height- and weight-matched healthy controls. Strength of finger-extension and -flexion was measured using the Medical Research Council (MRC) scale. Radial, median and ulnar nerve sonographic cross-sectional area (CSA) and echogenicity, expressed by the hypoechoic fraction (HF), were determined. In ALS, finger extensors were significantly weaker than finger flexors. Sonographic evaluation revealed peripheral nerve atrophy, affecting various nerve segments in ALS. HF was unaltered. This systematic study confirmed a long-observed physical examination finding in ALS - weakness in finger-extension out of proportion to finger-flexion. This phenomenon was not related to any particular sonographic pattern of upper limb peripheral nerve alteration. In ALS, dissociated forearm muscle weakness could aid in the disease's diagnosis. Nerve ultrasound did not provide additional information on the differential involvement of finger-extension and finger-flexion strength. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail.

PubMed

Tokuyama, Minami A; Xu, Cindy; Fisher, Rebecca E; Wilson-Rawls, Jeanne; Kusumi, Kenro; Newbern, Jason M

2018-01-15

Peripheral nerves exhibit robust regenerative capabilities in response to selective injury among amniotes, but the regeneration of entire muscle groups following volumetric muscle loss is limited in birds and mammals. In contrast, lizards possess the remarkable ability to regenerate extensive de novo muscle after tail loss. However, the mechanisms underlying reformation of the entire neuromuscular system in the regenerating lizard tail are not completely understood. We have tested whether the regeneration of the peripheral nerve and neuromuscular junctions (NMJs) recapitulate processes observed during normal neuromuscular development in the green anole, Anolis carolinensis. Our data confirm robust axonal outgrowth during early stages of tail regeneration and subsequent NMJ formation within weeks of autotomy. Interestingly, NMJs are overproduced as evidenced by a persistent increase in NMJ density 120 and 250 days post autotomy (DPA). Substantial Myelin Basic Protein (MBP) expression could also be detected along regenerating nerves indicating that the ability of Schwann cells to myelinate newly formed axons remained intact. Overall, our data suggest that the mechanism of de novo nerve and NMJ reformation parallel, in part, those observed during neuromuscular development. However, the prolonged increase in NMJ number and aberrant muscle differentiation hint at processes specific to the adult response. An examination of the coordinated exchange between peripheral nerves, Schwann cells, and newly synthesized muscle of the regenerating neuromuscular system may assist in the identification of candidate molecules that promote neuromuscular recovery in organisms incapable of a robust regenerative response. Copyright © 2017 Elsevier Inc. All rights reserved.

Osteoporosis and body composition.

PubMed

Crepaldi, G; Romanato, G; Tonin, P; Maggi, S

2007-01-01

The Epidemiologic Study on the Prevalence of Osteoporosis in Italy showed that the prevalence of osteoporosis among women and men aged 60 yr and over is 22.8% and 14.5%, respectively, giving rise to about 80,000 new fractures a yr. Sarcopenia is considered to be one of the main features of the aging process. It is characterized by a reduction in muscle mass and muscle strength, and affects women more than men. It is associated with a increased risk of fractures consequent upon a greater predisposition to falls, but also to the lack of bone remodeling due to reduced muscle mechanical strength. Muscle strength determines quality bone modifications such as density, strength, and microarchitecture. Variations in the ratios of cortical and muscle areas give rise to various types of osteoporosis, with different risks of fracture. Bone mineral density increases with body fat mass, and obesity has a protective effect against osteoporosis. This protective effect is explained by a combination of hormonal (peripheral aromatization of androgens to estrogens in adipose tissue) and mechanical factors (on weight-bearing bone sites), but the hormone leptin also probably mediates fat and bone mass. Serum leptin levels are closely related to body fat mass, and some findings suggest the peripheral effect of leptin, which exerts estrogenic effects, enhancing osteoblastic differentiation and inhibiting late adipocytic differentiation. The overall effect of leptin on bone results from a balance between negative central effects and positive direct peripheral effects, according to serum leptin levels.

Cerebral cortex activation mapping upon electrical muscle stimulation by 32-channel time-domain functional near-infrared spectroscopy.

PubMed

Re, Rebecca; Muthalib, Makii; Contini, Davide; Zucchelli, Lucia; Torricelli, Alessandro; Spinelli, Lorenzo; Caffini, Matteo; Ferrari, Marco; Quaresima, Valentina; Perrey, Stephane; Kerr, Graham

2013-01-01

The application of different EMS current thresholds on muscle activates not only the muscle but also peripheral sensory axons that send proprioceptive and pain signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was employed to map regional cortical activities under varied EMS current intensities applied on the right wrist extensor muscle. Eight healthy volunteers underwent four EMS at different current thresholds based on their individual maximal tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time courses of the absolute oxygenated and deoxygenated hemoglobin concentrations primarily over the bilateral sensorimotor cortical (SMC) regions were extrapolated, and cortical activation maps were determined by general linear model using the NIRS-SPM software. The stimulation-induced wrist extension paradigm significantly increased activation of the contralateral SMC region according to the EMS intensities, while the ipsilateral SMC region showed no significant changes. This could be due in part to a nociceptive response to the higher EMS current intensities and result also from increased sensorimotor integration in these cortical regions.

Skeletal muscle and nuclear hormone receptors: implications for cardiovascular and metabolic disease.

PubMed

Smith, Aaron G; Muscat, George E O

2005-10-01

Skeletal muscle is a major mass peripheral tissue that accounts for approximately 40% of the total body mass and a major player in energy balance. It accounts for >30% of energy expenditure, is the primary tissue of insulin stimulated glucose uptake, disposal, and storage. Furthermore, it influences metabolism via modulation of circulating and stored lipid (and cholesterol) flux. Lipid catabolism supplies up to 70% of the energy requirements for resting muscle. However, initial aerobic exercise utilizes stored muscle glycogen but as exercise continues, glucose and stored muscle triglycerides become important energy substrates. Endurance exercise increasingly depends on fatty acid oxidation (and lipid mobilization from other tissues). This underscores the importance of lipid and glucose utilization as an energy source in muscle. Consequently skeletal muscle has a significant role in insulin sensitivity, the blood lipid profile, and obesity. Moreover, caloric excess, obesity and physical inactivity lead to skeletal muscle insulin resistance, a risk factor for the development of type II diabetes. In this context skeletal muscle is an important therapeutic target in the battle against cardiovascular disease, the worlds most serious public health threat. Major risk factors for cardiovascular disease include dyslipidemia, hypertension, obesity, sedentary lifestyle, and diabetes. These risk factors are directly influenced by diet, metabolism and physical activity. Metabolism is largely regulated by nuclear hormone receptors which function as hormone regulated transcription factors that bind DNA and mediate the patho-physiological regulation of gene expression. Metabolism and activity, which directly influence cardiovascular disease risk factors, are primarily driven by skeletal muscle. Recently, many nuclear receptors expressed in skeletal muscle have been shown to improve glucose tolerance, insulin resistance, and dyslipidemia. Skeletal muscle and nuclear receptors are rapidly emerging as critical targets in the battle against cardiovascular disease risk factors. Understanding the function of nuclear receptors in skeletal muscle has enormous pharmacological utility for the treatment of cardiovascular disease. This review focuses on the molecular regulation of metabolism by nuclear receptors in skeletal muscle in the context of dyslipidemia and cardiovascular disease.

Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes.

PubMed

Aoki, Kosuke; Nakao, Atsunori; Adachi, Takako; Matsui, Yasushi; Miyakawa, Shumpei

2012-01-01

Muscle contraction during short intervals of intense exercise causes oxidative stress, which can play a role in the development of overtraining symptoms, including increased fatigue, resulting in muscle microinjury or inflammation. Recently it has been said that hydrogen can function as antioxidant, so we investigated the effect of hydrogen-rich water (HW) on oxidative stress and muscle fatigue in response to acute exercise. Ten male soccer players aged 20.9 ± 1.3 years old were subjected to exercise tests and blood sampling. Each subject was examined twice in a crossover double-blind manner; they were given either HW or placebo water (PW) for one week intervals. Subjects were requested to use a cycle ergometer at a 75 % maximal oxygen uptake (VO2) for 30 min, followed by measurement of peak torque and muscle activity throughout 100 repetitions of maximal isokinetic knee extension. Oxidative stress markers and creatine kinase in the peripheral blood were sequentially measured. Although acute exercise resulted in an increase in blood lactate levels in the subjects given PW, oral intake of HW prevented an elevation of blood lactate during heavy exercise. Peak torque of PW significantly decreased during maximal isokinetic knee extension, suggesting muscle fatigue, but peak torque of HW didn't decrease at early phase. There was no significant change in blood oxidative injury markers (d-ROMs and BAP) or creatine kinease after exercise. Adequate hydration with hydrogen-rich water pre-exercise reduced blood lactate levels and improved exercise-induced decline of muscle function. Although further studies to elucidate the exact mechanisms and the benefits are needed to be confirmed in larger series of studies, these preliminary results may suggest that HW may be suitable hydration for athletes.

Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

PubMed Central

Richey, Joyce M.; Castro, Ana Valeria B.; Broussard, Josiane L.; Ionut, Viorica; Bergman, Richard N.

2015-01-01

Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance. PMID:25852002

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle

PubMed Central

Yim, Peter D.; Gallos, George; Perez-zoghbi, Jose F.; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W.

2014-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K+ channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders. PMID:24662476

Peripheral denervation participates in heterotopic ossification in a spinal cord injury model

PubMed Central

Salga, Marjorie; Begot, Laurent; Holy, Xavier; Chedik, Malha; de l’Escalopier, Nicolas; Torossian, Fréderic; Levesque, Jean-Pierre; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline; Genêt, François

2017-01-01

We previously reported the development of a new acquired neurogenic HO (NHO) mouse model, combining spinal cord transection (SCI) and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage are still to be elucidated. In this study, we first hypothesized that peripheral nervous system (PNS) might convey pathological signals from injured spinal cord to muscles in NHO mouse model. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signaling pathways. Twenty one C57Bl6 mice were included in this protocol. Bilateral cardiotoxin (CTX) injection in hamstring muscles was associated with a two-stage surgical procedure, combining thoracic SCI with unilateral peripheral denervation. Volumes of HO (Bone Volume, BV) were measured 28 days after surgery using micro-computed tomography imaging techniques and histological analyses were made to confirm intramuscular osteogenesis. Volume comparisons were conducted between right and left hind limb of each animal, using a Wilcoxon signed rank test. Quantitative polymerase chain reaction (qPCR) was performed to explore intra muscular expression of BMP2, Alk3 and Id1. Nineteen mice survive the complete SCI and peripheral denervation procedure. When CTX injections were done right after surgery (n = 7), bilateral HO were detected in all animals after 28 days. Micro-CT measurements showed significantly increased BV in denervated paws (1.47 mm3 +/- 0.5) compared to contralateral sides (0.56 mm3 +/-0.4), p = 0.03. When peripheral denervation and CTX injections were performed after sham SCI surgery (n = 6), bilateral HO were present in three mice at day 28. Quantitative PCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice (shamSCI). Peripheral denervation can be reliably added to spinal cord transection in NHO mouse model. This new experimental design confirms that neuro inflammatory mechanisms induced by central or peripheral nervous system injury plays a key role in triggering ectopic osteogenesis. PMID:28854256

The relationship of muscle perfusion and metabolism with cardiovascular variables before and after detomidine injection during propofol-ketamine anaesthesia in horses.

PubMed

Edner, Anna; Nyman, Görel; Essén-Gustavsson, Birgitta

2002-10-01

To study in horses (1) the relationship between cardiovascular variables and muscle perfusion during propofol-ketamine anaesthesia, (2) the physiological effects of a single intravenous (IV) detomidine injection, (3) the metabolic response of muscle to anaesthesia, and (4) the effects of propofol-ketamine infusion on respiratory function. Prospective experimental study. Seven standardbred trotters, 5-12 years old, 416-581 kg. Anaesthesia was induced with intravenous (IV) guaifenesin and propofol (2 mg kg -1 ) and maintained with a continuous IV infusion of propofol (0.15 mg kg -1 minute -1 ) and ketamine (0.05 mg kg -1 minute -1 ) with horses positioned in left lateral recumbency. After 1 hour, detomidine (0.01 mg kg -1 ) was administered IV and 40-50 minutes later anaesthesia was discontinued. Cardiovascular and respiratory variables (heart rate, cardiac output, systemic and pulmonary artery blood pressures, respiratory rate, tidal volume, and inspiratory and expiratory O 2 and CO 2 ) and muscle temperature were measured at pre-determined times. Peripheral perfusion was measured continuously in the gluteal muscles and skin using laser Doppler flowmetry (LDF). Muscle biopsy samples from the left and right gluteal muscles were analysed for glycogen, creatine phosphate, creatine, adenine nucleotides, inosine monophosphate and lactate. Arterial blood was analysed for PO 2 , PCO 2 , pH, oxygen saturation and HCO 3 . Mixed venous blood was analysed for PO 2 , PCO 2 , pH, oxygen saturation, HCO 3 , cortisol, lactate, uric acid, hypoxanthine, xanthine, creatine kinase, creatinine, aspartate aminotransferase, electrolytes, total protein, haemoglobin, haematocrit and white blood cell count. Circulatory function was preserved during propofol-ketamine anaesthesia. Detomidine caused profound hypertension and bradycardia and decreased cardiac output and muscle perfusion. Ten minutes after detomidine injection muscle perfusion had recovered to pre-injection levels, although heart rate and cardiac output had not. No difference in indices of muscle metabolism was found between dependent and independent muscles. Anaerobic muscle metabolism, indicated by decreased muscle and creatine phosphate levels was evident after anaesthesia. Muscle perfusion was closely related to cardiac output but not arterial blood pressure. Total intravenous anaesthesia with propofol-ketamine deserves further study despite its respiratory depression effects, as the combination preserves cardiovascular function. Decreases in high-energy phosphate stores during recovery show that muscle is vulnerable after anaesthesia. Continued research is required to clarify the course of muscle metabolic events during recovery. Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Autoimmune paraneoplastic syndromes associated to lung cancer: A systematic review of the literature Part 4: Neurological paraneoplastic syndromes, involving the peripheral nervous system and the neuromuscular junction and muscles.

PubMed

Ruelle, Lucien; Bentea, Georgiana; Sideris, Spyridon; El Koulali, Mohamed; Holbrechts, Stéphane; Lafitte, Jean-Jacques; Grigoriu, Bogdan; Sculier, Claudine; Meert, Anne-Pascale; Durieux, Valérie; Berghmans, Thierry; Sculier, Jean-Paul

2017-09-01

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes that can complicate lung cancer appears useful. This article is the fourth of a series of five and deals mainly with neurological paraneoplastic syndromes involving the peripheral nervous system and the neuromuscular junction and muscles. Copyright © 2017 Elsevier B.V. All rights reserved.

Fusimotor control of spindle sensitivity regulates central and peripheral coding of joint angles.

PubMed

Lan, Ning; He, Xin

2012-01-01

Proprioceptive afferents from muscle spindles encode information about peripheral joint movements for the central nervous system (CNS). The sensitivity of muscle spindle is nonlinearly dependent on the activation of gamma (γ) motoneurons in the spinal cord that receives inputs from the motor cortex. How fusimotor control of spindle sensitivity affects proprioceptive coding of joint position is not clear. Furthermore, what information is carried in the fusimotor signal from the motor cortex to the muscle spindle is largely unknown. In this study, we addressed the issue of communication between the central and peripheral sensorimotor systems using a computational approach based on the virtual arm (VA) model. In simulation experiments within the operational range of joint movements, the gamma static commands (γ(s)) to the spindles of both mono-articular and bi-articular muscles were hypothesized (1) to remain constant, (2) to be modulated with joint angles linearly, and (3) to be modulated with joint angles nonlinearly. Simulation results revealed a nonlinear landscape of Ia afferent with respect to both γ(s) activation and joint angle. Among the three hypotheses, the constant and linear strategies did not yield Ia responses that matched the experimental data, and therefore, were rejected as plausible strategies of spindle sensitivity control. However, if γ(s) commands were quadratically modulated with joint angles, a robust linear relation between Ia afferents and joint angles could be obtained in both mono-articular and bi-articular muscles. With the quadratic strategy of spindle sensitivity control, γ(s) commands may serve as the CNS outputs that inform the periphery of central coding of joint angles. The results suggest that the information of joint angles may be communicated between the CNS and muscles via the descending γ(s) efferent and Ia afferent signals.

New continuous-flow total artificial heart and vascular permeability.

PubMed

Feng, Jun; Cohn, William E; Parnis, Steven M; Sodha, Neel R; Clements, Richard T; Sellke, Nicholas; Frazier, O Howard; Sellke, Frank W

2015-12-01

We tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability. Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10-25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin, and CD31 were analyzed by immunohistochemistry. There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho-VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance. There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability. Copyright © 2015 Elsevier Inc. All rights reserved.

Increased Interstitial Concentrations of Glutamate and Pyruvate in Vastus Lateralis of Women with Fibromyalgia Syndrome Are Normalized after an Exercise Intervention – A Case-Control Study

PubMed Central

Gerdle, Björn; Ernberg, Malin; Mannerkorpi, Kaisa; Larsson, Britt; Kosek, Eva; Christidis, Nikolaos; Ghafouri, Bijar

2016-01-01

Background Fibromyalgia syndrome (FMS) is associated with central alterations, but controversies exist regarding the presence and role of peripheral factors. Microdialysis (MD) can be used in vivo to study muscle alterations in FMS. Furthermore for chronic pain conditions such as FMS, the mechanisms for the positive effects of exercise are unclear. This study investigates the interstitial concentrations of algesics and metabolites in the vastus lateralis muscle of 29 women with FMS and 28 healthy women before and after an exercise intervention. Methods All the participants went through a clinical examination and completed a questionnaire. In addition, their pressure pain thresholds (PPTs) in their upper and lower extremities were determined. For both groups, MD was conducted in the vastus lateralis muscle before and after a 15-week exercise intervention of mainly resistance training of the lower limbs. Muscle blood flow and interstitial muscle concentrations of lactate, pyruvate, glutamate, glucose, and glycerol were determined. Results FMS was associated with significantly increased interstitial concentrations of glutamate, pyruvate, and lactate. After the exercise intervention, the FMS group exhibited significant decreases in pain intensity and in mean interstitial concentrations of glutamate, pyruvate, and glucose. The decrease in pain intensity in FMS correlated significantly with the decreases in pyruvate and glucose. In addition, the FMS group increased their strength and endurance. Conclusion This study supports the suggestion that peripheral metabolic and algesic muscle alterations are present in FMS patients and that these alterations contribute to pain. After an exercise intervention, alterations normalized, pain intensity decreased (but not abolished), and strength and endurance improved, all findings that suggest the effects of exercise are partially peripheral. PMID:27695113

Impact of rs361072 in the phosphoinositide 3-kinase p110beta gene on whole-body glucose metabolism and subunit protein expression in skeletal muscle.

PubMed

Ribel-Madsen, Rasmus; Poulsen, Pernille; Holmkvist, Johan; Mortensen, Brynjulf; Grarup, Niels; Friedrichsen, Martin; Jørgensen, Torben; Lauritzen, Torsten; Wojtaszewski, Jørgen F P; Pedersen, Oluf; Hansen, Torben; Vaag, Allan

2010-04-01

Phosphoinositide 3-kinase (PI3K) is a major effector in insulin signaling. rs361072, located in the promoter of the gene (PIK3CB) for the p110beta subunit, has previously been found to be associated with homeostasis model assessment for insulin resistance (HOMA-IR) in obese subjects. The aim was to investigate the influence of rs361072 on in vivo glucose metabolism, skeletal muscle PI3K subunit protein levels, and type 2 diabetes. The functional role of rs361072 was studied in 196 Danish healthy adult twins. Peripheral and hepatic insulin sensitivity was assessed by a euglycemic-hyperinsulinemic clamp. Basal and insulin-stimulated biopsies were taken from the vastus lateralis muscle, and tissue p110beta and p85alpha proteins were measured by Western blotting. The genetic association with type 2 diabetes and quantitative metabolic traits was investigated in 9,316 Danes with glucose tolerance ranging from normal to overt type 2 diabetes. While hepatic insulin resistance was similar in the fasting state, carriers of the minor G allele had lower hepatic glucose output (per-allele effect: -16%, P(add) = 0.004) during high physiological insulin infusion. rs361072 did not associate with insulin-stimulated peripheral glucose disposal despite a decreased muscle p85alpha:p110beta protein ratio (P(add) = 0.03) in G allele carriers. No association with HOMA-IR or type 2 diabetes (odds ratio 1.07, P = 0.5) was identified, and obesity did not interact with rs361072 on these traits. Our study suggests that the minor G allele of PIK3CB rs361072 associates with decreased muscle p85alpha:p110beta ratio and lower hepatic glucose production at high plasma insulin levels. However, no impact on type 2 diabetes prevalence was found.

Biochemical factors modulating female genital sexual arousal physiology.

PubMed

Traish, Abdulmaged M; Botchevar, Ella; Kim, Noel N

2010-09-01

Female genital sexual arousal responses are complex neurophysiological processes consisting of central and peripheral components that occur following sexual stimulation. The peripheral responses in sexual arousal include genital vasocongestion, engorgement and lubrication resulting from a surge of vaginal and clitoral blood flow. These hemodynamic events are mediated by a host of neurotransmitters and vasoactive agents. To discuss the role of various biochemical factors modulating female genital sexual arousal responses. A comprehensive literature review was conducted using the PubMed database and citations were selected, based on topical relevance, and examined for study methodology and major findings. Data from peer-reviewed publications. Adrenergic as well as non-adrenergic non-cholinergic neurotransmitters play an important role in regulating genital physiological responses by mediating vascular and non-vascular smooth muscle contractility. Vasoactive peptides and neuropeptides also modulate genital sexual responses by regulating vascular and non-vascular smooth muscle cells and epithelial function. The endocrine milieu, particularly sex steroid hormones, is critical in the maintenance of tissue structure and function. Reduced levels of estrogens and androgen are associated with dramatic alterations in genital tissue structure, including the nerve network, as well as the response to physiological modulators. Furthermore, estrogen and androgen deficiency is associated with reduced expression of sex steroid receptors and most importantly with attenuated genital blood flow and lubrication in response to pelvic nerve stimulation. This article provides an integrated framework describing the physiological and molecular basis of various pathophysiological conditions associated with female genital sexual arousal dysfunction. © 2010 International Society for Sexual Medicine.

The role of exercise testing in heart failure.

PubMed

Swedberg, K; Gundersen, T

1993-01-01

The objectives of exercise testing in congestive heart failure (CHF) may be summarized as follows: (a) detect impaired cardiac performance, (b) grade severity of cardiac failure and classify functional capability, and (c) assess effects of interventions. Several different methods are available to make these assessments, and we have to ask ourselves how well exercise testing achieves these objectives. It has to be kept in mind that the power generated by the exercising muscles is dependent on the oxygen delivery to the skeletal muscles. Oxygen uptake is the result of an integrated performance of the lungs, heart, and peripheral circulation. In patients, as well as in normal subjects, oxygen uptake is related to hemodynamic indices such as cardiac output, stroke volume, or exercise duration when a stepwise regulated maximal exercise protocol is used. However, there are major differences in the concept of a true maximum in normal subjects versus heart failure patients. Fit-normal subjects will achieve a real maximal oxygen uptake, whereas patients may stop testing before a maximum is reached because of symptoms such as dyspnea or leg fatigue. Therefore, it is better if the actual oxygen uptake can be measured. "Peak" rather than true maximal oxygen uptake has been suggested for the classification of the severity of heart failure. Peripheral factors modify the cardiac output through such factors as vascular resistance, organ function, and hormonal release. Maximal exercise will stress the cardiovascular system to a point where the weakest chain will impose a limiting effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue engineering the mechanosensory circuit of the stretch reflex arc: sensory neuron innervation of intrafusal muscle fibers.

PubMed

Rumsey, John W; Das, Mainak; Bhalkikar, Abhijeet; Stancescu, Maria; Hickman, James J

2010-11-01

The sensory circuit of the stretch reflex arc, composed of specialized intrafusal muscle fibers and type Ia proprioceptive sensory neurons, converts mechanical information regarding muscle length and stretch to electrical action potentials and relays them to the central nervous system. Utilizing a non-biological substrate, surface patterning photolithography and a serum-free medium formulation a co-culture system was developed that facilitated functional interactions between intrafusal muscle fibers and sensory neurons. The presence of annulospiral wrappings (ASWs) and flower-spray endings (FSEs), both physiologically relevant morphologies in sensory neuron-intrafusal fiber interactions, were demonstrated and quantified using immunocytochemistry. Furthermore, two proposed components of the mammalian mechanosensory transduction system, BNaC1 and PICK1, were both identified at the ASWs and FSEs. To verify functionality of the mechanoreceptor elements the system was integrated with a MEMS cantilever device, and Ca(2+) currents were imaged along the length of an axon innervating an intrafusal fiber when stretched by cantilever deflection. This system provides a platform for examining the role of this mechanosensory complex in the pathology of myotonic and muscular dystrophies, peripheral neuropathy, and spasticity inducing diseases like Parkinson's. These studies will also assist in engineering fine motor control for prosthetic devices by improving our understanding of mechanosensitive feedback. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Electrical stimulation of transplanted motoneurons improves motor unit formation

PubMed Central

Liu, Yang; Grumbles, Robert M.

2014-01-01

Motoneurons die following spinal cord trauma and with neurological disease. Intact axons reinnervate nearby muscle fibers to compensate for the death of motoneurons, but when an entire motoneuron pool dies, there is complete denervation. To reduce denervation atrophy, we have reinnervated muscles in Fisher rats from local transplants of embryonic motoneurons in peripheral nerve. Since growth of axons from embryonic neurons is activity dependent, our aim was to test whether brief electrical stimulation of the neurons immediately after transplantation altered motor unit numbers and muscle properties 10 wk later. All surgical procedures and recordings were done in anesthetized animals. The muscle consequences of motoneuron death were mimicked by unilateral sciatic nerve section. One week later, 200,000 embryonic day 14 and 15 ventral spinal cord cells, purified for motoneurons, were injected into the tibial nerve 10–15 mm from the gastrocnemii muscles as the only neuron source for muscle reinnervation. The cells were stimulated immediately after transplantation for up to 1 h using protocols designed to examine differential effects due to pulse number, stimulation frequency, pattern, and duration. Electrical stimulation that included short rests and lasted for 1 h resulted in higher motor unit counts. Muscles with higher motor unit counts had more reinnervated fibers and were stronger. Denervated muscles had to be stimulated directly to evoke contractions. These results show that brief electrical stimulation of embryonic neurons, in vivo, has long-term effects on motor unit formation and muscle force. This muscle reinnervation provides the opportunity to use patterned electrical stimulation to produce functional movements. PMID:24848463

Muscle glucose metabolism in chronic obstructive pulmonary disease patients.

PubMed

Sancho-Muñoz, Antonio; Trampal, Carlos; Pascual, Sergi; Martínez-Llorens, Juana; Chalela, Roberto; Gea, Joaquim; Orozco-Levi, Mauricio

2014-06-01

Muscle dysfunction is one of the most extensively studied manifestations of COPD. Metabolic changes in muscle are difficult to study in vivo, due to the lack of non-invasive techniques. Our aim was to evaluate metabolic activity simultaneously in various muscle groups in COPD patients. Thirty-nine COPD patients and 21 controls with normal lung function, due to undergo computed axial and positron emission tomography for staging of localized lung lesions were included. After administration of 18-fluordeoxyglucose, images of 2 respiratory muscles (costal and crural diaphragm, and rectus abdominus) and 2 peripheral muscles (brachial biceps and quadriceps) were obtained, using the standard uptake value as the glucose metabolism index. Standard uptake value was higher in both portions of the diaphragm than in the other muscles of all subjects. Moreover, the crural diaphragm and rectus abdominus showed greater activity in COPD patients than in the controls (1.8±0.7 vs 1.4±0.8; and 0.78±0.2 vs 0.58±0.1; respectively, P<.05). A similar trend was observed with the quadriceps. In COPD patients, uptake in the two respiratory muscles and the quadriceps correlated directly with air trapping (r=0.388, 0.427 and 0.361, respectively, P<.05). There is greater glucose uptake and metabolism in the human diaphragm compared to other muscles when the subject is at rest. Increased glucose metabolism in the respiratory muscles (with a similar trend in their quadriceps) of COPD patients is confirmed quantitatively, and is directly related to the mechanical loads confronted. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Common questions about the diagnosis and management of fibromyalgia.

PubMed

Kodner, Charles

2015-04-01

Fibromyalgia has a distinct pathophysiology involving central amplification of peripheral sensory signals. Core symptoms are chronic widespread pain, fatigue, and sleep disturbance. Most patients with fibromyalgia have muscle pain and tenderness, forgetfulness or problems concentrating, and significant functional limitations. Fibromyalgia is diagnosed using an updated set of clinical criteria that no longer depend on tender point examination; laboratory testing may rule out other disorders that commonly present with fatigue, such as anemia and thyroid disease. Patients with fibromyalgia should be evaluated for comorbid functional pain syndromes and mood disorders. Management of fibromyalgia should include patient education, symptom relief, and regular aerobic physical activity. Serotoninnorepinephrine reuptake inhibitors, tricyclic antidepressants, antiepileptics, and muscle relaxants have the strongest evidence of benefit for improving pain, fatigue, sleep symptoms, and quality of life. Multiple complementary and alternative medicine therapies have been used but have limited evidence of effectiveness. Opioids should be used to relieve pain in carefully selected patients only if alternative therapies are ineffective.

[The bionic hand].

PubMed

Surke, Carsten; Ducommun Dit Boudry, Pascal; Vögelin, Esther

2015-08-01

The loss of the upper extremity implicates a grave insult in the life of the involved person. To compensate for the loss of function different powered prosthetic devices are available. Ever since their first development 70 years ago numerous improvements in terms of size, weight and wearing comfort have been developed, but issues regarding the control of upper extremity prostheses remain. Slow grasping speed, limited grip positions and especially failure to provide a sensory feedback limit the acceptance in patients. Recent developments are aimed to allow a more intuitive control of the prosthetic device and to provide a sensory feedback to the amputee. Targeted reinnervation reassignes existing muscles to different peripheral nerves thereby enabling them to fulfill alternate functions. Implanting electrodes into muscle bellies of the forearm allows a more accurate control of the prosthesis. Promising results are being achieved by implanting nerve electrodes by establishing bilateral communication between patient and prosthesis. The following review summarizes the current developments of bionic prostheses in the upper extremity.

The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation

PubMed Central

Park, So Young; Jang, So Young; Shin, Yoon Kyoung; Jung, Dong Keun; Yoon, Byeol A; Kim, Jong Kook; Jo, Young Rae; Lee, Hye Jeong

2017-01-01

The vertebrate neuromuscular junction (NMJ) is considered as a “tripartite synapse” consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system. PMID:28680299

Serotonin Improves High Fat Diet Induced Obesity in Mice.

PubMed

Watanabe, Hitoshi; Nakano, Tatsuya; Saito, Ryo; Akasaka, Daisuke; Saito, Kazuki; Ogasawara, Hideki; Minashima, Takeshi; Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Inoue, Nao; Ikeda, Ikuo; Chen, Xiangning; Miyake, Masato; Kitazawa, Haruki; Shirakawa, Hitoshi; Sato, Kan; Tahara, Kohji; Nagasawa, Yuya; Rose, Michael T; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

2016-01-01

There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation.

PubMed

Park, So Young; Jang, So Young; Shin, Yoon Kyoung; Jung, Dong Keun; Yoon, Byeol A; Kim, Jong Kook; Jo, Young Rae; Lee, Hye Jeong; Park, Hwan Tae

2017-06-01

The vertebrate neuromuscular junction (NMJ) is considered as a "tripartite synapse" consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system.

Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method.

PubMed

Manevska, Nevena; Stojanoski, Sinisa; Pop Gjorceva, Daniela; Todorovska, Lidija; Miladinova, Daniela; Zafirova, Beti

2017-09-01

Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation.

Muscle and Liver Carbohydrates: Response to Military Task Performance by Women and Men

DTIC Science & Technology

2000-10-01

rapidly synthesize glycogen from three-carbon compounds generated by muscle metabolism and taken up by the liver ( gluconeogenesis ). 20 UNPUBLISHED DATA...49008 Glial cell line-derived neturotrophic factor (GDNF) is a recently discovered nerrotrophic factor that afflets peripheral motor neurons . Increased

Feedforward neural control of toe walking in humans.

PubMed

Lorentzen, Jakob; Willerslev-Olsen, Maria; Hüche Larsen, Helle; Svane, Christian; Forman, Christian; Frisk, Rasmus; Farmer, Simon Francis; Kersting, Uwe; Nielsen, Jens Bo

2018-03-23

Activation of ankle muscles at ground contact during toe walking is unaltered when sensory feedback is blocked or the ground is suddenly dropped. Responses in the soleus muscle to transcranial magnetic stimulation, but not peripheral nerve stimulation, are facilitated at ground contact during toe walking. We argue that toe walking is supported by feedforward control at ground contact. Toe walking requires careful control of the ankle muscles in order to absorb the impact of ground contact and maintain a stable position of the joint. The present study aimed to clarify the peripheral and central neural mechanisms involved. Fifteen healthy adults walked on a treadmill (3.0 km h -1 ). Tibialis anterior (TA) and soleus (Sol) EMG, knee and ankle joint angles, and gastrocnemius-soleus muscle fascicle lengths were recorded. Peripheral and central contributions to the EMG activity were assessed by afferent blockade, H-reflex testing, transcranial magnetic brain stimulation (TMS) and sudden unloading of the planter flexor muscle-tendon complex. Sol EMG activity started prior to ground contact and remained high throughout stance. TA EMG activity, which is normally seen around ground contact during heel strike walking, was absent. Although stretch of the Achilles tendon-muscle complex was observed after ground contact, this was not associated with lengthening of the ankle plantar flexor muscle fascicles. Sol EMG around ground contact was not affected by ischaemic blockade of large-diameter sensory afferents, or the sudden removal of ground support shortly after toe contact. Soleus motor-evoked potentials elicited by TMS were facilitated immediately after ground contact, whereas Sol H-reflexes were not. These findings indicate that at the crucial time of ankle stabilization following ground contact, toe walking is governed by centrally mediated motor drive rather than sensory driven reflex mechanisms. These findings have implications for our understanding of the control of human gait during voluntary toe walking. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin-α2-deficient mouse model of congenital muscular dystrophy

PubMed Central

Homma, Sachiko; Beermann, Mary Lou; Miller, Jeffrey Boone

2011-01-01

The most common form of childhood congenital muscular dystrophy, Type 1A (MDC1A), is caused by mutations in the human LAMA2 gene that encodes the laminin-α2 subunit. In addition to skeletal muscle deficits, MDC1A patients typically show a loss of peripheral nerve function. To identify the mechanisms underlying this loss of nerve function, we have examined pathology and cell differentiation in sciatic nerves and ventral roots of the laminin-α2-deficient (Lama2−/−) mice, which are models for MDC1A. We found that, compared with wild-type, sciatic nerves of Lama2−/− mice had a significant increase in both proliferating (Ki67+) cells and premyelinating (Oct6+) Schwann cells, but also had a significant decrease in both immature/non-myelinating [glial fibrillary acidic protein (GFAP)+] and myelinating (Krox20+) Schwann cells. To extend our previous work in which we found that doxycycline, which has multiple effects on mammalian cells, improves motor behavior and more than doubles the median life-span of Lama2−/− mice, we also determined how nerve pathology was affected by doxycycline treatment. We found that myelinating (Krox20+) Schwann cells were significantly increased in doxycycline-treated compared with untreated sciatic nerves. In addition, doxycycline-treated peripheral nerves had significantly less pathology as measured by assays such as amount of unmyelinated or disorganized axons. This study thus identified aberrant proliferation and differentiation of Schwann cells as key components of pathogenesis in peripheral nerves and provided proof-of-concept that pharmaceutical therapy can be of potential benefit for peripheral nerve dysfunction in MDC1A. PMID:21505075

Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity

PubMed Central

D'Amico, Jessica M.; Condliffe, Elizabeth G.; Martins, Karen J. B.; Bennett, David J.; Gorassini, Monica A.

2014-01-01

The state of areflexia and muscle weakness that immediately follows a spinal cord injury (SCI) is gradually replaced by the recovery of neuronal and network excitability, leading to both improvements in residual motor function and the development of spasticity. In this review we summarize recent animal and human studies that describe how motoneurons and their activation by sensory pathways become hyperexcitable to compensate for the reduction of functional activation of the spinal cord and the eventual impact on the muscle. Specifically, decreases in the inhibitory control of sensory transmission and increases in intrinsic motoneuron excitability are described. We present the idea that replacing lost patterned activation of the spinal cord by activating synaptic inputs via assisted movements, pharmacology or electrical stimulation may help to recover lost spinal inhibition. This may lead to a reduction of uncontrolled activation of the spinal cord and thus, improve its controlled activation by synaptic inputs to ultimately normalize circuit function. Increasing the excitation of the spinal cord with spared descending and/or peripheral inputs by facilitating movement, instead of suppressing it pharmacologically, may provide the best avenue to improve residual motor function and manage spasticity after SCI. PMID:24860447

Muscle Spindle Traffic in Functionally Unstable Ankles During Ligamentous Stress

PubMed Central

Needle, Alan R.; Charles B. (Buz), Swanik; Farquhar, William B.; Thomas, Stephen J.; Rose, William C.; Kaminski, Thomas W.

2013-01-01

Context: Ankle sprains are common in athletes, with functional ankle instability (FAI) developing in approximately half of cases. The relationship between laxity and FAI has been inconclusive, suggesting that instability may be caused by insufficient sensorimotor function and dynamic restraint. Research has suggested that deafferentation of peripheral mechanoreceptors potentially causes FAI; however, direct evidence confirming peripheral sensory deficits has been elusive because previous investigators relied upon subjective proprioceptive tests. Objective: To develop a method for simultaneously recording peripheral sensory traffic, joint forces, and laxity and to quantify differences between healthy ankles and those with reported instability. Design: Case-control study. Setting: University laboratory. Patients or Other Participants: A total of 29 participants (age = 20.9 ± 2.2 years, height = 173.1 ± 8.9 cm, mass = 74.5 ± 12.7 kg) stratified as having healthy (HA, n = 19) or unstable ankles (UA, n = 10). Intervention(s): Sensory traffic from muscle spindle afferents in the peroneal nerve was recorded with microneurography while anterior (AP) and inversion (IE) stress was applied to ligamentous structures using an ankle arthrometer under test and sham conditions. Main Outcome Measure(s): Laxity (millimeters or degrees) and amplitude of sensory traffic (percentage) were determined at 0, 30, 60, 90, and 125 N of AP force and at 0, 1, 2, 3, and 4 Nm of IE torque. Two-factor repeated-measures analyses of variance were used to determine differences between groups and conditions. Results: No differences in laxity were observed between groups (P > .05). Afferent traffic increased with increased force and torque in test trials (P < .001). The UA group displayed decreased afferent activity at 30 N of AP force compared with the HA group (HA: 30.2% ± 9.9%, UA: 17.1% ± 16.1%, P < .05). Conclusions: The amplitude of sensory traffic increased simultaneously with greater ankle motion and loading, providing evidence of the integrated role of capsuloligamentous and musculotendinous mechanoreceptors in maintaining joint sensation. Unstable ankles demonstrated diminished afferent traffic at low levels of force, suggesting the early detection of joint loading may be compromised. PMID:23672383

A randomized controlled trial of a mixed Kinesio taping-compression technique on venous symptoms, pain, peripheral venous flow, clinical severity and overall health status in postmenopausal women with chronic venous insufficiency.

PubMed

Aguilar-Ferrándiz, M Encarnación; Castro-Sánchez, Adelaida María; Matarán-Peñarrocha, Guillermo A; Guisado-Barrilao, Rafael; García-Ríos, M Carmen; Moreno-Lorenzo, Carmen

2014-01-01

To investigate the effect of a mixed Kinesio taping treatment in women with chronic venous insufficiency. A double-blinded randomized clinical trial. Clinical setting. One hundred and twenty postmenopausal women with mild-moderate chronic venous insufficiency were randomly assigned to an experimental group receiving standardized Kinesio taping treatment for gastrocnemius muscle enhancement and ankle functional correction, or to a placebo control group for simulated Kinesio taping. MAIN OUTCOMES VARIABLES: Venous symptoms, pain, photoplethysmographic measurements, bioelectrical impedance, temperature, severity and overall health were recorded at baseline and after four weeks of treatment. The 2 × 2 mixed model ANCOVA with repeated measurements showed statistically significant group * time interaction for heaviness (F = 22.99, p = 0.002), claudication (F = 8.57, p = 0.004), swelling (F = 22.58, p = 0.001), muscle cramps (F = 7.14, p = 0.008), venous refill time (right: F = 9.45, p = 0.023; left: F = 14.86, p = 0.001), venous pump function (right: F = 35.55, p = 0.004; left: F = 17.39 p = 0.001), extracellular water (right: F = 35.55, p = 0.004; left: F = 23.84, p = 0.001), severity (F = 18.47, p = 0.001), physical function (F = 9.15, p = 0.003) and body pain (F = 3.36, p = 0.043). Both groups reported significant reduction in pain. Mixed Kinesio taping-compression therapy improves symptoms, peripheral venous flow and severity and slightly increases overall health status in females with mild chronic venous insufficiency. Kinesio taping may have a placebo effect on pain.

The Influence of Body Mass Index, Sex, & Muscle Activation on Pressure Distribution During Lateral Falls on the Hip.

PubMed

Pretty, Steven P; Martel, Daniel R; Laing, Andrew C

2017-12-01

Hip fracture incidence rates are influenced by body mass index (BMI) and sex, likely through mechanistic pathways that influence dynamics of the pelvis-femur system during fall-related impacts. The goal of this study was to extend our understanding of these impact dynamics by investigating the effects of BMI, sex, and local muscle activation on pressure distribution over the hip region during lateral impacts. Twenty participants underwent "pelvis-release experiments" (which simulate a lateral fall onto the hip), including muscle-'relaxed' and 'contracted' trials. Males and low-BMI individuals exhibited 44 and 55% greater peak pressure, as well as 66 and 56% lower peripheral hip force, compared to females and high-BMI individuals, respectively. Local muscle activation increased peak force by 10%, contact area by 17%, and peripheral hip force by 11% compared to relaxed trials. In summary, males and low-BMI individuals exhibited more concentrated loading over the greater trochanter. Muscle activation increased peak force, but this force was distributed over a larger area, preventing increased localized loading over the greater trochanter. These findings suggest potential value in incorporating sex, gender, and muscle activation-specific force distributions as inputs into computational tissue-level models, and have implications for the design of personalized protective devices including wearable hip protectors.

The digastric muscle is less involved in pharyngeal swallowing in rabbits.

PubMed

Tsujimura, Takanori; Yamada, Aki; Nakamura, Yuki; Fukuhara, Takako; Yamamura, Kensuke; Inoue, Makoto

2012-06-01

The swallowing reflex is centrally programmed by the lower brain stem, the so-called swallowing central pattern generator (CPG), and once the reflex is initiated, many muscles in the oral, pharyngeal, laryngeal, and esophageal regions are systematically activated. The mylohyoid (MH) muscle has been considered to be a "leading muscle" according to previous studies, but the functional role of the digastric (DIG) muscle in the swallowing reflex remains unclear. In the present study, therefore, the activities of single units of MH and DIG neurons were recorded extracellularly, and the functional involvement of these neurons in the swallowing reflex was investigated. The experiments were carried out on eight adult male Japanese white rabbits anesthetized with urethane. To identify DIG and MH neurons, the peripheral nerve (either DIG or MH) was stimulated to evoke action potentials of single motoneurons. Motoneurons were identified as such if they either (1) responded to antidromic nerve stimulation of DIG or MH in an all-or-none manner at threshold intensities and (2) followed stimulation frequencies of up to 0.5 kHz. As a result, all 11 MH neurons recorded were synchronously activated during the swallowing reflex, while there was no activity in any of the 7 DIG neurons recorded during the swallowing reflex. All neurons were anatomically localized ventromedially at the level of the caudal portion of the trigeminal motor nucleus, and there were no differences between the MH and DIG neuron sites. The present results strongly suggest that at least in the rabbit, DIG motoneurons are not tightly controlled by the swallowing CPG and, hence, the DIG muscle is less involved in the swallowing reflex.

Serotonergic and peptidergic modulation of the buccal mass protractor muscle (I2) in aplysia.

PubMed

Hurwitz, I; Cropper, E C; Vilim, F S; Alexeeva, V; Susswein, A J; Kupfermann, I; Weiss, K R

2000-12-01

Plasticity of Aplysia feeding has largely been measured by noting changes in radula protraction. On the basis of previous work, it has been suggested that peripheral modulation may contribute to behavioral plasticity. However, peripheral plasticity has not been demonstrated in the neuromuscular systems that participate in radula protraction. Therefore in this study we investigated whether contractions of a major radula protraction muscle (I2) are subject to modulation. We demonstrate, first, that an increase in the firing frequency of the cholinergic I2 motoneurons will increase the amplitude of the resulting muscle contraction but will not modulate its relaxation rate. We show, second, that neuronal processes on the I2 muscle are immunoreactive to myomodulin (MM), RFamide, and serotonin (5-HT), but not to small cardioactive peptide (SCP) or buccalin. The I2 motoneurons B31, B32, B61, and B62 are not immunoreactive to RFamide, 5-HT, SCP, or buccalin. However, all four cells are MM immunoreactive and are capable of synthesizing MMa. Third, we show that the bioactivity of the different modulators is somewhat different; while the MMs (i.e., MMa and MMb) and 5-HT increase I2 muscle relaxation rate, and potentiate muscle contraction amplitude, MMa, at high concentrations, depresses muscle contractions. Fourth, our data suggest that cAMP at least partially mediates effects of modulators on contraction amplitude and relaxation rate.

Whole-mount Confocal Microscopy for Adult Ear Skin: A Model System to Study Neuro-vascular Branching Morphogenesis and Immune Cell Distribution.

PubMed

Yamazaki, Tomoko; Li, Wenling; Mukouyama, Yoh-Suke

2018-03-29

Here, we present a protocol of a whole-mount adult ear skin imaging technique to study comprehensive three-dimensional neuro-vascular branching morphogenesis and patterning, as well as immune cell distribution at a cellular level. The analysis of peripheral nerve and blood vessel anatomical structures in adult tissues provides some insights into the understanding of functional neuro-vascular wiring and neuro-vascular degeneration in pathological conditions such as wound healing. As a highly informative model system, we have focused our studies on adult ear skin, which is readily accessible for dissection. Our simple and reproducible protocol provides an accurate depiction of the cellular components in the entire skin, such as peripheral nerves (sensory axons, sympathetic axons, and Schwann cells), blood vessels (endothelial cells and vascular smooth muscle cells), and inflammatory cells. We believe this protocol will pave the way to investigate morphological abnormalities in peripheral nerves and blood vessels as well as the inflammation in the adult ear skin under different pathological conditions.

Electrical stimulation of paralyzed vibrissal muscles reduces endplate reinnervation and does not promote motor recovery after facial nerve repair in rats.

PubMed

Sinis, Nektarios; Horn, Frauke; Genchev, Borislav; Skouras, Emmanouil; Merkel, Daniel; Angelova, Srebrina K; Kaidoglou, Katerina; Michael, Joern; Pavlov, Stoyan; Igelmund, Peter; Schaller, Hans-Eberhard; Irintchev, Andrey; Dunlop, Sarah A; Angelov, Doychin N

2009-10-01

The outcome of peripheral nerve injuries requiring surgical repair is poor. Recent work has suggested that electrical stimulation (ES) of denervated muscles could be beneficial. Here we tested whether ES has a positive influence on functional recovery after injury and surgical repair of the facial nerve. Outcomes at 2 months were compared to animals receiving sham stimulation (SS). Starting on the first day after end-to-end suture (facial-facial anastomosis), electrical stimulation (square 0.1 ms pulses at 5 Hz at an ex tempore established threshold amplitude of between 3.0 and 5.0V) was delivered to the vibrissal muscles for 5 min a day, 3 times a week. Restoration of vibrissal motor performance following ES or SS was evaluated using the video-based motion analysis and correlated with the degree of collateral axonal branching at the lesion site, the number of motor endplates in the target musculature and the quality of their reinnervation, i.e. the degree of mono- versus poly-innervation. Neither protocol reduced collateral branching. ES did not improve functional outcome, but rather reduced the number of innervated motor endplates to approximately one-fifth of normal values and failed to reduce the proportion of poly-innervated motor endplates. We conclude that ES is not beneficial for recovery of whisker function after facial nerve repair in rats.

Diagnostic electron microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dickersin, G.R.

1988-01-01

In this book the author presents a comprehensive reference text on diagnostic electron microscopy. Throughout the book he illustrates how ultrastructural identification can be helpful for the recognition of cell type and the identification of mechanisms of pathogenesis in various diseases. In addition to electron microscopy photographs, there are also numerous light microscopy photographs for comparison. This text presents the classification of neoplasms in the order and arrangement most familiar to the pathologist. Contents: Introduction; Diagram of a Normal Cell; Normal Cell Function; Embryology; Neoplasms; Infectious Agents; Metabolic Diseases; Renal Diseases; Skeletal Muscle and Peripheral Nerve Diseases; Index.

Use of tripolar electrodes for minimization of current spread in uncut peripheral nerve stimulation.

PubMed

Ohsawa, Ichiro; Inui, Koji

2009-05-01

The electrical stimulation of an uncut peripheral nerve requires a countermeasure to avoid the spread of current through a loop pathway formed outside the electrode array. Here the use of tripolar electrodes (TE) is proposed. By binding the two end poles, current spread through the loop pathway can theoretically be eliminated since both end poles are held equipotential. Experimentally, we tested the validity of this approach. In chloralose-urethane anesthetized rats, the left cervical vagus (LCV) was placed on TE which could function as such or as bipolar electrodes (BE) by the use of a selector switch. The spread of current to the adjacent tissues (rectus capitis muscle underlying the LCV, and the right cervical vagus (RCV) incised and translocated beside the target, LCV) was compared between TE and BE. When the stimulus intensity was increased, contraction occurred in the capitis muscle with BE, but not TE. Compound spike potentials of A fiber origin were evoked in the non-target RCV on high-intensity stimulation with BE, but not TE. Constant voltage stimulation of the LCV with TE produced bradycardia of the same magnitude as that with BE. In conclusion, constant voltage stimulation using TE can minimize current spread without changing the stimulus's effects.

Axonal Regeneration after Sciatic Nerve Lesion Is Delayed but Complete in GFAP- and Vimentin-Deficient Mice

PubMed Central

Berg, Alexander; Zelano, Johan; Pekna, Marcela; Wilhelmsson, Ulrika; Pekny, Milos; Cullheim, Staffan

2013-01-01

Peripheral axotomy of motoneurons triggers Wallerian degeneration of injured axons distal to the lesion, followed by axon regeneration. Centrally, axotomy induces loss of synapses (synaptic stripping) from the surface of lesioned motoneurons in the spinal cord. At the lesion site, reactive Schwann cells provide trophic support and guidance for outgrowing axons. The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process. We studied axonal regeneration and synaptic stripping of motoneurons after a sciatic nerve lesion in mice lacking the intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin, which are upregulated in reactive astrocytes and Schwann cells. Seven days after sciatic nerve transection, ultrastructural analysis of synaptic density on the somata of injured motoneurons revealed more remaining boutons covering injured somata in GFAP–/–Vim–/– mice. After sciatic nerve crush in GFAP–/–Vim–/– mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete. Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics. PMID:24223940

The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion.

PubMed

Marasco, Paul D; Bourbeau, Dennis J; Shell, Courtney E; Granja-Vazquez, Rafael; Ina, Jason G

2017-01-01

Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing.

The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion

PubMed Central

Marasco, Paul D.; Bourbeau, Dennis J.; Shell, Courtney E.; Granja-Vazquez, Rafael; Ina, Jason G.

2017-01-01

Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing. PMID:29182648

Effect of eccentric exercise with reduced muscle glycogen on plasma interleukin-6 and neuromuscular responses of musculus quadriceps femoris.

PubMed

Gavin, James P; Myers, Stephen D; Willems, Mark E T

2016-07-01

Eccentric exercise can result in muscle damage and interleukin-6 (IL-6) secretion. Glycogen availability is a potent stimulator of IL-6 secretion. We examined effects of eccentric exercise in a low-glycogen state on neuromuscular function and plasma IL-6 secretion. Twelve active men (23 ± 4 yr, 179 ± 5 cm, 77 ± 10 kg, means ± SD) completed two downhill treadmill runs (gradient, -12%, 5 × 8 min; speed, 12.1 ± 1.1 km/h) with normal (NG) and reduced muscle glycogen (RG) in randomized order and at least 6 wk apart. Muscle glycogen was reduced using an established cycling protocol until exhaustion and dietary manipulation the evening before the morning run. Physiological responses were measured up to 48 h after the downhill runs. During recovery, force deficits of musculus quadriceps femoris by maximal isometric contractions were similar. Changes in low-frequency fatigue were larger with RG. Voluntary activation and plasma IL-6 levels were similar in recovery between conditions. It is concluded that unaccustomed, damaging eccentric exercise with low muscle glycogen of the m. quadriceps femoris 1) exacerbated low-frequency fatigue but 2) had no additional effect on IL-6 secretion. Neuromuscular impairment after eccentric exercise with low muscle glycogen appears to have a greater peripheral component in early recovery. Copyright © 2016 the American Physiological Society.

Physiology of Normal Esophageal Motility

PubMed Central

Goyal, Raj K; Chaudhury, Arun

2009-01-01

The esophagus consists of two different parts. In humans, the cervical esophagus is composed of striated muscles and the thoracic esophagus is composed of phasic smooth muscles. The striated muscle esophagus is innervated by the lower motor neurons and peristalsis in this segment is due to sequential activation of the motor neurons in the nucleus ambiguus. Both primary and secondary peristaltic contractions are centrally mediated. The smooth muscle of esophagus is phasic in nature and is innervated by intramural inhibitory (nitric oxide releasing) and excitatory (acetylcholine releasing) neurons that receive inputs from separate sets of preganglionic neurons located in the dorsal motor nucleus of vagus. The primary peristalsis in this segment involves both central and peripheral mechanisms. The primary peristalsis consist of inhibition (called deglutitive inhibition) followed by excitation. The secondary peristalsis is entirely due to peripheral mechanisms and also involves inhibition followed by excitation. The lower esophageal sphincter (LES) is characterized by tonic muscle that is different from the muscle of the esophageal body. The LES, like the esophageal body smooth muscle, is also innervated by the inhibitory and excitatory neurons. The LES maintains tonic closure due to its myogenic property. The LES tone is modulated by the inhibitory and the excitatory nerves. Inhibitory nerves mediate LES relaxation and the excitatory nerves mediate reflex contraction or rebound contraction of the LES. Clinical disorders of esophageal motility can be classified on the basis of disorders of the inhibitory and excitatory innervations and the smooth muscles. PMID:18364578

A review of concepts regarding the origin of respiratory muscle fatigue

NASA Astrophysics Data System (ADS)

Kuraszkiewicz, Bożena; Piotrkiewicz, Maria

2011-01-01

In this review, the classification of respiratory muscle fatigue from the perspective of its origin is presented. The fatigue is classified as central or peripheral, and the latter further subdivided into high- and low-frequency fatigue. However, muscle fatigue is a complex process and all three types of fatigue probably occur simultaneously in the overloaded respiratory muscles. The relative importance of each type depends on the duration of respiratory loading and other physiological variables. However, central and high-frequency fatigue resolve rapidly once muscle overload is removed, whereas low-frequency fatigue persists over long time.

Mitochondrial Respiration after One Session of Calf Raise Exercise in Patients with Peripheral Vascular Disease and Healthy Older Adults

PubMed Central

Wohlwend, Martin; Rognmo, Øivind; Mattsson, Erney J. R.

2016-01-01

Purpose Mitochondria are essential for energy production in the muscle cell and for this they are dependent upon a sufficient supply of oxygen by the circulation. Exercise training has shown to be a potent stimulus for physiological adaptations and mitochondria play a central role. Whether changes in mitochondrial respiration are seen after exercise in patients with a reduced circulation is unknown. The aim of the study was to evaluate the time course and whether one session of calf raise exercise stimulates mitochondrial respiration in the calf muscle of patients with peripheral vascular disease. Methods One group of patients with peripheral vascular disease (n = 11) and one group of healthy older adults (n = 11) were included. Patients performed one session of continuous calf raises followed by 5 extra repetitions after initiation of pain. Healthy older adults performed 100 continuous calf raises. Gastrocnemius muscle biopsies were collected at baseline and 15 minutes, one hour, three hours and 24 hours after one session of calf raise exercise. A multi substrate (octanoylcarnitine, malate, adp, glutamate, succinate, FCCP, rotenone) approach was used to analyze mitochondrial respiration in permeabilized fibers. Mixed-linear model for repeated measures was used for statistical analyses. Results Patients with peripheral vascular disease have a lower baseline respiration supported by complex I and they increase respiration supported by complex II at one hour post-exercise. Healthy older adults increase respiration supported by electron transfer flavoprotein and complex I at one hour and 24 hours post-exercise. Conclusion Our results indicate a shift towards mitochondrial respiration supported by complex II as being a pathophysiological component of peripheral vascular disease. Furthermore exercise stimulates mitochondrial respiration already after one session of calf raise exercise in patients with peripheral vascular disease and healthy older adults. Trial Registration ClinicalTrials.gov NCT01842412 PMID:27760222

Why the chameleon has spiral-shaped muscle fibres in its tongue

PubMed Central

Leeuwen, J. L. van

1997-01-01

The intralingual accelerator muscle is the primary actuator for the remarkable ballistic tongue projection of the chameleon. At rest, this muscle envelopes the elongated entoglossal process, a cylindrically shaped bone with a tapering distal end. During tongue projection, the accelerator muscle elongates and slides forward along the entoglossal process until the entire muscle extends beyond the distal end of the process. The accelerator muscle fibres are arranged in transverse planes (small deviations are possible), and form (hitherto unexplained) spiral-shaped arcs from the peripheral to the internal boundary. To initiate tongue projection, the muscle fibres probably generate a high intramuscular pressure. The resulting negative pressure gradient (from base to tip) causes the muscle to elongate and to accelerate forward. Effective forward sliding is made possible by a lubricant and a relatively low normal stress exerted on the proximal cylindrical part of the entoglossal process. A relatively high normal stress is, however, probably required for an effective acceleration of muscle tissue over the tapered end of the process. For optimal performance, the fast extension movement should occur without significant (energy absorbing) torsional motion of the tongue. In addition, the tongue extension movement is aided by a close packing of the muscles fibres (required for a high power density) and a uniform strain and work output in every cross-section of the muscle. A quantitative model of the accelerator muscle was developed that predicts internal muscle fibre arrangements based on the functional requirements above and the physical principle of mechanical stability. The curved shapes and orientations of the muscle fibres typically found in the accelerator muscle were accurately predicted by the model. Furthermore, the model predicts that the reduction of the entoglossal radius towards the tip (and thus the internal radius of the muscle) tends to increase the normal stress on the entoglossal bone.

Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes.

PubMed

Hagberg, Carolina E; Mehlem, Annika; Falkevall, Annelie; Muhl, Lars; Fam, Barbara C; Ortsäter, Henrik; Scotney, Pierre; Nyqvist, Daniel; Samén, Erik; Lu, Li; Stone-Elander, Sharon; Proietto, Joseph; Andrikopoulos, Sofianos; Sjöholm, Ake; Nash, Andrew; Eriksson, Ulf

2012-10-18

The prevalence of type 2 diabetes is rapidly increasing, with severe socioeconomic impacts. Excess lipid deposition in peripheral tissues impairs insulin sensitivity and glucose uptake, and has been proposed to contribute to the pathology of type 2 diabetes. However, few treatment options exist that directly target ectopic lipid accumulation. Recently it was found that vascular endothelial growth factor B (VEGF-B) controls endothelial uptake and transport of fatty acids in heart and skeletal muscle. Here we show that decreased VEGF-B signalling in rodent models of type 2 diabetes restores insulin sensitivity and improves glucose tolerance. Genetic deletion of Vegfb in diabetic db/db mice prevented ectopic lipid deposition, increased muscle glucose uptake and maintained normoglycaemia. Pharmacological inhibition of VEGF-B signalling by antibody administration to db/db mice enhanced glucose tolerance, preserved pancreatic islet architecture, improved β-cell function and ameliorated dyslipidaemia, key elements of type 2 diabetes and the metabolic syndrome. The potential use of VEGF-B neutralization in type 2 diabetes was further elucidated in rats fed a high-fat diet, in which it normalized insulin sensitivity and increased glucose uptake in skeletal muscle and heart. Our results demonstrate that the vascular endothelium can function as an efficient barrier to excess muscle lipid uptake even under conditions of severe obesity and type 2 diabetes, and that this barrier can be maintained by inhibition of VEGF-B signalling. We propose VEGF-B antagonism as a novel pharmacological approach for type 2 diabetes, targeting the lipid-transport properties of the endothelium to improve muscle insulin sensitivity and glucose disposal.

Sustained Local Release of NGF from a Chitosan-Sericin Composite Scaffold for Treating Chronic Nerve Compression.

PubMed

Zhang, Lei; Yang, Wen; Tao, Kaixiong; Song, Yu; Xie, Hongjian; Wang, Jian; Li, Xiaolin; Shuai, Xiaoming; Gao, Jinbo; Chang, Panpan; Wang, Guobin; Wang, Zheng; Wang, Lin

2017-02-01

Chronic nerve compression (CNC), a common form of peripheral nerve injury, always leads to chronic peripheral nerve pain and dysfunction. Current available treatments for CNC are ineffective as they usually aim to alleviate symptoms at the acute phase with limited capability toward restoring injured nerve function. New approaches for effective recovery of CNC injury are highly desired. Here we report for the first time a tissue-engineered approach for the repair of CNC. A genipin cross-linked chitosan-sericin 3D scaffold for delivering nerve growth factor (NGF) was designed and fabricated. This scaffold combines the advantages of both chitosan and sericin, such as high porosity, adjustable mechanical properties and swelling ratios, the ability of supporting Schwann cells growth, and improving nerve regeneration. The degradation products of the composite scaffold upregulate the mRNA levels of the genes important for facilitating nerve function recovery, including glial-derived neurotrophic factor (GDNF), early growth response 2 (EGR2), and neural cell adhesion molecule (NCAM) in Schwann cells, while down-regulating two inflammatory genes' mRNA levels in macrophages, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β). Importantly, our tissue-engineered strategy achieves significant nerve functional recovery in a preclinical CNC animal model by decreasing neuralgia, improving nerve conduction velocity (NCV), accelerating microstructure restoration, and attenuating gastrocnemius muscles dystrophy. Together, this work suggests a promising clinical alternative for treating chronic peripheral nerve compression injury.

Asynchronous oscillations of two zebrafish CLOCK partners reveal differential clock control and function

PubMed Central

Cermakian, Nicolas; Whitmore, David; Foulkes, Nicholas S.; Sassone-Corsi, Paolo

2000-01-01

Most clock genes encode transcription factors that interact to elicit cooperative control of clock function. Using a two-hybrid system approach, we have isolated two different partners of zebrafish (zf) CLOCK, which are similar to the mammalian BMAL1 (brain and muscle arylhydrocarbon receptor nuclear translocator-like protein 1). The two homologs, zfBMAL1 and zfBMAL2, contain conserved basic helix–loop–helix-PAS (Period-Arylhydrocarbon receptor-Singleminded) domains but diverge in the carboxyl termini, thus bearing different transcriptional activation potential. As for zfClock, the expression of both zfBmals oscillates in most tissues in the animal. However, in many tissues, the peak, levels, and kinetics of expression are different between the two genes and for the same gene from tissue to tissue. These results support the existence of independent peripheral oscillators and suggest that zfBMAL1 and zfBMAL2 may exert distinct circadian functions, interacting differentially with zfCLOCK at various times in different tissues. Our findings also indicate that multiple controls may be exerted by the central clock and/or that peripheral oscillators can differentially interpret central clock signals. PMID:10760301

Muscle Activation During Peripheral Nerve Field Stimulation Occurs Due to Recruitment of Efferent Nerve Fibers, Not Direct Muscle Activation.

PubMed

Frahm, Ken Steffen; Hennings, Kristian; Vera-Portocarrero, Louis; Wacnik, Paul W; Mørch, Carsten Dahl

2016-08-01

Peripheral nerve field stimulation (PNFS) is a potential treatment for chronic low-back pain. Pain relief using PNFS is dependent on activation of non-nociceptive Aβ-fibers. However, PNFS may also activate muscles, causing twitches and discomfort. In this study, we developed a mathematical model, to investigate the activation of sensory and motor nerves, as well as direct muscle fiber activation. The extracellular field was estimated using a finite element model based on the geometry of CT scanned lumbar vertebrae. The electrode was modeled as being implanted to a depth of 10-15 mm. Three implant directions were modeled; horizontally, vertically, and diagonally. Both single electrode and "between-lead" stimulation between contralateral electrodes were modeled. The extracellular field was combined with models of sensory Aβ-nerves, motor neurons and muscle fibers to estimate their activation thresholds. The model showed that sensory Aβ fibers could be activated with thresholds down to 0.563 V, and the lowest threshold for motor nerve activation was 7.19 V using between-lead stimulation with the cathode located closest to the nerves. All thresholds for direct muscle activation were above 500 V. The results suggest that direct muscle activation does not occur during PNFS, and concomitant motor and sensory nerve fiber activation are only likely to occur when using between-lead configuration. Thus, it may be relevant to investigate the location of the innervation zone of the low-back muscles prior to electrode implantation to avoid muscle activation. © 2016 International Neuromodulation Society.

Natural mediotrusive contact: does it affect the masticatory and neck EMG activity during tooth grinding?

PubMed

Fuentes, Aler D; Martin, Conchita; Bull, Ricardo; Santander, Hugo; Gutiérrez, Mario F; Miralles, Rodolfo

2015-12-29

There is scarce knowledge regarding the influence of a natural mediotrusive contact on mandibular and cervical muscular activity. The purpose of this study was to analyze the EMG activity of the anterior temporalis (AT) and sternocleidomastoid (SCM) muscles during awake grinding in healthy subjects with or without a natural mediotrusive occlusal contact. 15 subjects with natural mediotrusive occlusal contact (Group 1) and 15 subjects without natural mediotrusive occlusal contact (Group 2) participated. Bilateral surface EMG activity of AT and SCM muscles was recorded during unilateral eccentric or concentric tooth grinding tasks. EMG activity was normalized against the activity recorded during maximal voluntary clenching in intercuspal position (IP) for AT muscles and during maximal intentional isometric head-neck rotation to each side, for SCM muscles. EMG activity of AT and SCM muscles showed no statistical difference between groups. EMG activity of AT muscle was higher in the working side (WS) than in the non-WS (NWS) in Group 1 during concentric grinding (0.492 vs 0.331, P = 0.047), whereas no difference was observed in Group 2. EMG activity of SCM was similar between working and NWSs in both groups and tasks. Asymmetry indexes (AIs) were not significantly different between groups. These findings in healthy subjects support the assumption that during awake tooth grinding, central nerve control predominates over peripheral inputs, and reinforce the idea of a functional link between the motor-neuron pools that control jaw and neck muscles.

Natural mediotrusive contact: does it affect the masticatory and neck EMG activity during tooth grinding?

PubMed

Fuentes, Aler D; Martin, Conchita; Bull, Ricardo; Santander, Hugo; Gutiérrez, Mario F; Miralles, Rodolfo

2016-07-01

There is scarce knowledge regarding the influence of a natural mediotrusive contact on mandibular and cervical muscular activity. The purpose of this study was to analyze the EMG activity of the anterior temporalis (AT) and sternocleidomastoid (SCM) muscles during awake grinding in healthy subjects with or without a natural mediotrusive occlusal contact. Fifteen subjects with natural mediotrusive occlusal contact (Group 1) and 15 subjects without natural mediotrusive occlusal contact (Group 2) participated. Bilateral surface EMG activity of AT and SCM muscles was recorded during unilateral eccentric or concentric tooth grinding tasks. EMG activity was normalized against the activity recorded during maximal voluntary clenching in intercuspal position (IP) for AT muscles and during maximal intentional isometric head-neck rotation to each side, for SCM muscles. EMG activity of AT and SCM muscles showed no statistical difference between groups. EMG activity of AT muscle was higher in the working side (WS) than in the non-WS (NWS) in Group 1 during concentric grinding (0.492 vs 0.331, p = 0.047), whereas no difference was observed in Group 2. EMG activity of SCM was similar between working and NWSs in both groups and tasks. Asymmetry indexes (AIs) were not significantly different between groups. These findings in healthy subjects support the assumption that during awake tooth grinding, central nerve control predominates over peripheral inputs, and reinforce the idea of a functional link between the motor-neuron pools that control jaw and neck muscles.

Non-invasive peripheral nerve stimulation via focused ultrasound in vivo

NASA Astrophysics Data System (ADS)

Downs, Matthew E.; Lee, Stephen A.; Yang, Georgiana; Kim, Seaok; Wang, Qi; Konofagou, Elisa E.

2018-02-01

Focused ultrasound (FUS) has been employed on a wide range of clinical applications to safely and non-invasively achieve desired effects that have previously required invasive and lengthy procedures with conventional methods. Conventional electrical neuromodulation therapies that are applied to the peripheral nervous system (PNS) are invasive and/or non-specific. Recently, focused ultrasound has demonstrated the ability to modulate the central nervous system and ex vivo peripheral neurons. Here, for the first time, noninvasive stimulation of the sciatic nerve eliciting a physiological response in vivo is demonstrated with FUS. FUS was applied on the sciatic nerve in mice with simultaneous electromyography (EMG) on the tibialis anterior muscle. EMG signals were detected during or directly after ultrasound stimulation along with observable muscle contraction of the hind limb. Transecting the sciatic nerve downstream of FUS stimulation eliminated EMG activity during FUS stimulation. Peak-to-peak EMG response amplitudes and latency were found to be comparable to conventional electrical stimulation methods. Histology along with behavioral and thermal testing did not indicate damage to the nerve or surrounding regions. The findings presented herein demonstrate that FUS can serve as a targeted, safe and non-invasive alternative to conventional peripheral nervous system stimulation to treat peripheral neuropathic diseases in the clinic.

Drosophila-Cdh1 (Rap/Fzr) a regulatory subunit of APC/C is required for synaptic morphology, synaptic transmission and locomotion.

PubMed

Wise, Alexandria; Schatoff, Emma; Flores, Julian; Hua, Shao-Ying; Ueda, Atsushi; Wu, Chun-Fang; Venkatesh, Tadmiri

2013-11-01

The assembly of functional synapses requires the orchestration of the synthesis and degradation of a multitude of proteins. Protein degradation and modification by the conserved ubiquitination pathway has emerged as a key cellular regulatory mechanism during nervous system development and function (Kwabe and Brose, 2011). The anaphase promoting complex/cyclosome (APC/C) is a multi-subunit ubiquitin ligase complex primarily characterized for its role in the regulation of mitosis (Peters, 2002). In recent years, a role for APC/C in nervous system development and function has been rapidly emerging (Stegmuller and Bonni, 2005; Li et al., 2008). In the mammalian central nervous system the activator subunit, APC/C-Cdh1, has been shown to be a regulator of axon growth and dendrite morphogenesis (Konishi et al., 2004). In the Drosophila peripheral nervous system (PNS), APC2, a ligase subunit of the APC/C complex has been shown to regulate synaptic bouton size and activity (van Roessel et al., 2004). To investigate the role of APC/C-Cdh1 at the synapse we examined loss-of-function mutants of Rap/Fzr (Retina aberrant in pattern/Fizzy related), a Drosophila homolog of the mammalian Cdh1 during the development of the larval neuromuscular junction in Drosophila. Our cell biological, ultrastructural, electrophysiological, and behavioral data showed that rap/fzr loss-of-function mutations lead to changes in synaptic structure and function as well as locomotion defects. Data presented here show changes in size and morphology of synaptic boutons, and, muscle tissue organization. Electrophysiological experiments show that loss-of-function mutants exhibit increased frequency of spontaneous miniature synaptic potentials, indicating a higher rate of spontaneous synaptic vesicle fusion events. In addition, larval locomotion and peristaltic movement were also impaired. These findings suggest a role for Drosophila APC/C-Cdh1 mediated ubiquitination in regulating synaptic morphology, function and integrity of muscle structure in the peripheral nervous system. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Calf enlargement associated with neurologic disease: two uncommon cases.

PubMed

Harwood, S C; Honet, J C

1988-01-01

Muscle enlargement and hypertrophy are rare findings in neurogenic lesions. The two in combination have been reported in cases of peripheral nerve lesions, polyneuropathy, and poliomyelitis. True and pseudo muscle hypertrophy are the two possible etiologies, whereas infiltration, stretch, or exercise of the muscle are the causative factors. We report two cases of unilateral calf enlargement, one occurring after surgery for S1 radiculopathy with associated cramping, and the other after poliomyelitis.

Evoked Potentials to Evaluate Mechanisms of Peripheral Nerve Repair.

DTIC Science & Technology

1980-02-01

brass bar. The tibial pin was clamped to vertical bars which in turn were adjustable and could be fixed to longitudinal runners. Muscle contraction was...each muscle contraction recording. After establishing stimulus threshold, supramaximal stimuli were spaced from 1.5 to 2.0 per second. A series of single...hour to 52 weeks after injury. Limbs with mobilized non- injured nerves sustained small but definite decreases in muscle contraction str:?ngth

Netrin-1 controls sympathetic arterial innervation.

PubMed

Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J C; Kennedy, Timothy E; Zhuang, Zhen; Simons, Michael; Levy, Bernard I; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

2014-07-01

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.

Netrin-1 controls sympathetic arterial innervation

PubMed Central

Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J.C.; Kennedy, Timothy E.; Zhuang, Zhen; Simons, Michael; Levy, Bernard I.; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

2014-01-01

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type–specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs. PMID:24937433

Exercise hyperaemia: magnitude and aspects on regulation in humans

PubMed Central

Saltin, Bengt

2007-01-01

The primary function of the cardiovascular system is to supply oxygen to tissues and organs in the body. When muscles contract the aerobic demands are met by an increase in oxygen delivery both at the systemic and the regional levels, a match that is very close and holds at submaximal exercise and when small muscle group contract also at vigorous intensities. The level of muscle perfusion reached is 250 ml min−1 (100 g)−1 in muscle of sedentary subjects and in endurance-trained athletes 400 ml min−1 (100 g)−1 has been reported. These levels of peak exercise hyperaemia equal what has been observed in other species. One consequence of these high muscle blood flows is that the human heart cannot support an optimal blood flow in whole body exercise (arms and legs combined) and sympathetically mediated vasoconstriction, also in arterioles feeding active limb muscles, contributes to matching peripheral resistance in order to maintain blood pressure. Respiratory muscles appear to have a higher priority for a blood flow than limb and torso muscles. There is no consensus in regard to which locally produced substances elicit the vasodilatation when muscle contracts. In addition to NO, data are presented for various metabolites of arachidonic acid and also on ATP, possibly released from the red cells. Using blockers of nitric oxide synthase (l-NMMA or l-NAME) and the enzymes producing epoxyeicosatrienoic acid (EET) (sulpaphenozole or tetraetylammonium chloride) or prostaglandins (indomethacin), muscle blood flow may be reduced by up to 25–40%. Evaluating the exact role of ATP has to await further studies in humans and especially the use of specific ATP receptor blockers. PMID:17640931

Myosin Light Chain Kinase and the Role of Myosin Light Chain Phosphorylation in Skeletal Muscle

PubMed Central

Stull, James T.; Kamm, Kristine E.; Vandenboom, Rene

2011-01-01

Skeletal muscle myosin light chain kinase (skMLCK) is a dedicated Ca2+/calmodulin-dependent serine-threonine protein kinase that phosphorylates the regulatory light chain (RLC) of sarcomeric myosin. It is expressed from the MYLK2 gene specifically in skeletal muscle fibers with most abundance in fast contracting muscles. Biochemically, activation occurs with Ca2+ binding to calmodulin forming a (Ca2+)4•calmodulin complex sufficient for activation with a diffusion limited, stoichiometic binding and displacement of a regulatory segment from skMLCK catalytic core. The N-terminal sequence of RLC then extends through the exposed catalytic cleft for Ser15 phosphorylation. Removal of Ca2+ results in the slow dissociation of calmodulin and inactivation of skMLCK. Combined biochemical properties provide unique features for the physiological responsiveness of RLC phosphorylation, including (1) rapid activation of MLCK by Ca2+/calmodulin, (2) limiting kinase activity so phosphorylation is slower than contraction, (3) slow MLCK inactivation after relaxation and (4) much greater kinase activity relative to myosin light chain phosphatase (MLCP). SkMLCK phosphorylation of myosin RLC modulates mechanical aspects of vertebrate skeletal muscle function. In permeabilized skeletal muscle fibers, phosphorylation-mediated alterations in myosin structure increase the rate of force-generation by myosin cross bridges to increase Ca2+-sensitivity of the contractile apparatus. Stimulation-induced increases in RLC phosphorylation in intact muscle produces isometric and concentric force potentiation to enhance dynamic aspects of muscle work and power in unfatigued or fatigued muscle. Moreover, RLC phosphorylation-mediated enhancements may interact with neural strategies for human skeletal muscle activation to ameliorate either central or peripheral aspects of fatigue. PMID:21284933

Pacing Strategy, Muscle Fatigue, and Technique in 1500-m Speed-Skating and Cycling Time Trials.

PubMed

Stoter, Inge K; MacIntosh, Brian R; Fletcher, Jared R; Pootz, Spencer; Zijdewind, Inge; Hettinga, Florentina J

2016-04-01

To evaluate pacing behavior and peripheral and central contributions to muscle fatigue in 1500-m speed-skating and cycling time trials when a faster or slower start is instructed. Nine speed skaters and 9 cyclists, all competing at regional or national level, performed two 1500-m time trials in their sport. Athletes were instructed to start faster than usual in 1 trial and slower in the other. Mean velocity was measured per 100 m. Blood lactate concentrations were measured. Maximal voluntary contraction (MVC), voluntary activation (VA), and potentiated twitch (PT) of the quadriceps muscles were measured to estimate central and peripheral contributions to muscle fatigue. In speed skating, knee, hip, and trunk angles were measured to evaluate technique. Cyclists showed a more explosive start than speed skaters in the fast-start time trial (cyclists performed first 300 m in 24.70 ± 1.73 s, speed skaters in 26.18 ± 0.79 s). Both trials resulted in reduced MVC (12.0% ± 14.5%), VA (2.4% ± 5.0%), and PT (25.4% ± 15.2%). Blood lactate concentrations after the time trial and the decrease in PT were greater in the fast-start than in the slow-start trial. Speed skaters showed higher trunk angles in the fast-start than in the slow-start trial, while knee angles remained similar. Despite similar instructions, behavioral adaptations in pacing differed between the 2 sports, resulting in equal central and peripheral contributions to muscle fatigue in both sports. This provides evidence for the importance of neurophysiological aspects in the regulation of pacing. It also stresses the notion that optimal pacing needs to be studied sport specifically, and coaches should be aware of this.

Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation.

PubMed

Kumru, Hatice; Albu, Sergiu; Rothwell, John; Leon, Daniel; Flores, Cecilia; Opisso, Eloy; Tormos, Josep Maria; Valls-Sole, Josep

2017-10-01

Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS ('magnetic-PAS') on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle. Eleven healthy subjects underwent three 10min stimulation sessions: 10HzrPMS alone, applied in trains of 5 stimuli every 10s (60 trains) on the extensor carpi radialis (ECR) muscle; rTMS alone at an intensity 120% of ECR threshold, applied over motor cortex of ECR and at a frequency of 0.1Hz (60 stimuli) and magnetic PAS, i.e., paired rPMS and rTMS. We recorded motor evoked potentials (MEPs) from ECR and first dorsal interosseous (FDI) muscles. We measured resting motor threshold, motor evoked potentials (MEP) amplitude at 120% of RMT, short intracortical inhibition (SICI) at interstimulus interval (ISI) of 2ms and intracortical facilitation (ICF) at an ISI of 15ms before and immediately after each intervention. Magnetic-PAS , but not rTMS or rPMS applied separately, increased MEP amplitude and reduced short intracortical inhibition in ECR but not in FDI muscle. Magnetic-PAS can increase corticospinal excitability and reduce intracortical inhibition. The effects may be specific for the area of cortical representation of the stimulated muscle. Application of magnetic-PAS might be relevant for motor rehabilitation. Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.

Chronic phase advance alters circadian physiological rhythms and peripheral molecular clocks

PubMed Central

Wolff, Gretchen; Duncan, Marilyn J.

2013-01-01

Shifting the onset of light, acutely or chronically, can profoundly affect responses to infection, tumor progression, development of metabolic disease, and mortality in mammals. To date, the majority of phase-shifting studies have focused on acute exposure to a shift in the timing of the light cycle, whereas the consequences of chronic phase shifts alone on molecular rhythms in peripheral tissues such as skeletal muscle have not been studied. In this study, we tested the effect of chronic phase advance on the molecular clock mechanism in two phenotypically different skeletal muscles. The phase advance protocol (CPA) involved 6-h phase advances (earlier light onset) every 4 days for 8 wk. Analysis of the molecular clock, via bioluminescence recording, in the soleus and flexor digitorum brevis (FDB) muscles and lung demonstrated that CPA advanced the phase of the rhythm when studied immediately after CPA. However, if the mice were placed into free-running conditions (DD) for 2 wk after CPA, the molecular clock was not phase shifted in the two muscles but was still shifted in the lung. Wheel running behavior remained rhythmic in CPA mice; however, the endogenous period length of the free-running rhythm was significantly shorter than that of control mice. Core body temperature, cage activity, and heart rate remained rhythmic throughout the experiment, although the onset of the rhythms was significantly delayed with CPA. These results provide clues that lifestyles associated with chronic environmental desynchrony, such as shift work, can have disruptive effects on the molecular clock mechanism in peripheral tissues, including both types of skeletal muscle. Whether this can contribute, long term, to increased incidence of insulin resistance/metabolic disease requires further study. PMID:23703115

C3 toxin and poly-DL-lactide-ε-caprolactone conduits in the critically damaged peripheral nervous system: a combined therapeutic approach.

PubMed

Leibig, Nico; Boyle, Veronika; Kraus, Daniel; Stark, Gerhard Bjoern; Penna, Vincenzo

2015-03-01

Peripheral nerve regeneration over longer distances through conduits is limited. In the presented study, critical size nerve gap bridging with a poly-DL-lactide-ε-caprolactone (PLC) conduit was combined with application of C3 toxin to facilitate axonal sprouting. The PLC filled with fibrin (n = 10) and fibrin gel loaded with 1-μg C3-C2I and 2-μg C2II (n = 10) were compared to autologous nerve grafts (n = 10) in a 15-mm sciatic nerve gap lesion model of the rat. Functional and electrophysiological analyses were performed before histological evaluation. Evaluation of motor function and nerve conduction velocity at 16 weeks revealed no differences between the groups. All histological parameters and muscle weight were significantly elevated in nerve graft group. No differences were observed in both PLC groups. The PLCs are permissive for nerve regeneration over a 15-mm defect in rats. Intraluminal application of C3 toxin did not lead to significant enhancement of nerve sprouting.

Anorectal and Pelvic Pain

PubMed Central

Bharucha, Adil E.; Lee, Tae Hee

2016-01-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the three most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first two conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacologic, behavioral, and physical therapy. Opioids should not be avoided, and surgery has a limited role, primarily in refractory interstitial cystitis. PMID:27712641

Biomechanical and functional variation in rat sciatic nerve following cuff electrode implantation

PubMed Central

2014-01-01

Background Nerve cuff electrodes are commonly and successfully used for stimulating peripheral nerves. On the other hand, they occasionally induce functional and morphological changes following chronic implantation, for reasons not always clear. We hypothesize that restriction of nerve mobility due to cuff implantation may alter nerve conduction. Methods We quantified acute changes in nerve-muscle electrophysiology, using electromyography, and nerve kinematics in anesthetized Sprague Dawley rat sciatic nerves during controlled hindlimb joint movement. We compared electrophysiological and biomechanical response in uncuffed nerves and those secured within a cuff electrode using analysis of variance (ANOVA) and regression analysis. Results Tethering resulting from cuff implantation resulted in altered nerve strain and a complex biomechanical environment during joint movement. Coincident with biomechanical changes, electromyography revealed significantly increased variability in the response of conduction latency and amplitude in cuffed, but not free, nerves following joint movement. Conclusion Our findings emphasize the importance of the mechanical interface between peripheral nerves and their devices on neurophysiological performance. This work has implications for nerve device design, implantation, and prediction of long-term efficacy. PMID:24758405

BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.

PubMed

McClung, Joseph M; McCord, Timothy J; Ryan, Terence E; Schmidt, Cameron A; Green, Tom D; Southerland, Kevin W; Reinardy, Jessica L; Mueller, Sarah B; Venkatraman, Talaignair N; Lascola, Christopher D; Keum, Sehoon; Marchuk, Douglas A; Spangenburg, Espen E; Dokun, Ayotunde; Annex, Brian H; Kontos, Christopher D

2017-07-18

Critical limb ischemia is a manifestation of peripheral artery disease that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered 2 overlapping quantitative trait loci in mice, Lsq-1 and Civq-1 , that affected limb muscle survival and stroke volume after femoral artery or middle cerebral artery ligation, respectively. Here, we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hind-limb ischemia. We treated mice with either adeno-associated viruses encoding a control (green fluorescent protein) or 2 BAG3 (Bcl-2-associated athanogene-3) variants, namely Met81 or Ile81, and subjected the mice to hind-limb ischemia. We found that the BAG3 Ile81Met variant in the C57BL/6 (BL6) mouse background segregates with protection from tissue necrosis in a shorter congenic fragment of Lsq-1 (C.B6- Lsq1-3 ). BALB/c mice treated with adeno-associated virus encoding the BL6 BAG3 variant (Ile81; n=25) displayed reduced limb-tissue necrosis and increased limb tissue perfusion compared with Met81- (n=25) or green fluorescent protein- (n=29) expressing animals. BAG3 Ile81 , but not BAG3 Met81 , improved ischemic muscle myopathy and muscle precursor cell differentiation and improved muscle regeneration in a separate, toxin-induced model of injury. Systemic injection of adeno-associated virus-BAG3 Ile81 (n=9), but not BAG3 Met81 (n=10) or green fluorescent protein (n=5), improved ischemic limb blood flow and limb muscle histology and restored muscle function (force production). Compared with BAG3 Met81 , BAG3 Ile81 displayed improved binding to the small heat shock protein (HspB8) in ischemic skeletal muscle cells and enhanced ischemic muscle autophagic flux. Taken together, our data demonstrate that genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis. These results highlight a pathway that preserves tissue survival and muscle function in the setting of ischemia. © 2017 American Heart Association, Inc.

Interfacing with the nervous system: a review of current bioelectric technologies.

PubMed

Sahyouni, Ronald; Mahmoodi, Amin; Chen, Jefferson W; Chang, David T; Moshtaghi, Omid; Djalilian, Hamid R; Lin, Harrison W

2017-10-23

The aim of this study is to discuss the state of the art with regard to established or promising bioelectric therapies meant to alter or control neurologic function. We present recent reports on bioelectric technologies that interface with the nervous system at three potential sites-(1) the end organ, (2) the peripheral nervous system, and (3) the central nervous system-while exploring practical and clinical considerations. A literature search was executed on PubMed, IEEE, and Web of Science databases. A review of the current literature was conducted to examine functional and histomorphological effects of neuroprosthetic interfaces with a focus on end-organ, peripheral, and central nervous system interfaces. Innovations in bioelectric technologies are providing increasing selectivity in stimulating distinct nerve fiber populations in order to activate discrete muscles. Significant advances in electrode array design focus on increasing selectivity, stability, and functionality of implantable neuroprosthetics. The application of neuroprosthetics to paretic nerves or even directly stimulating or recording from the central nervous system holds great potential in advancing the field of nerve and tissue bioelectric engineering and contributing to clinical care. Although current physiotherapeutic and surgical treatments seek to restore function, structure, or comfort, they bear significant limitations in enabling cosmetic or functional recovery. Instead, the introduction of bioelectric technology may play a role in the restoration of function in patients with neurologic deficits.

Peripheral androgen receptors sustain the acrobatics and fine motor skill of elaborate male courtship.

PubMed

Fuxjager, Matthew J; Longpre, Kristy M; Chew, Jennifer G; Fusani, Leonida; Schlinger, Barney A

2013-09-01

Androgenic hormones regulate many aspects of animal social behavior, including the elaborate display routines on which many species rely for advertisement and competition. One way that this might occur is through peripheral effects of androgens, particularly on skeletal muscles that control complex movements and postures of the body and its limbs. However, the specific contribution of peripheral androgen-muscle interactions to the performance of elaborate behavioral displays in the natural world has never been examined. We study this issue in one of the only natural physiological models of animal acrobatics: the golden-collared manakin (Manacus vitellinus). In this tropical bird, males compete with each other and court females by producing firecracker-like wing- snaps and by rapidly dancing among saplings over the forest floor. To test how activation of peripheral androgen receptors (AR) influences this display, we treat reproductively active adult male birds with the peripherally selective antiandrogen bicalutamide (BICAL) and observe the effects of this manipulation on male display performance. We not only validate the peripheral specificity of BICAL in this species, but we also show that BICAL treatment reduces the frequency with which adult male birds perform their acrobatic display maneuvers and disrupts the overall structure and fine-scale patterning of these birds' main complex wing-snap sonation. In addition, this manipulation has no effect on the behavioral metrics associated with male motivation to display. Together, our findings help differentiate the various effects of peripheral and central AR on the performance of a complex sociosexual behavioral phenotype by indicating that peripheral AR can optimize the motor skills necessary for the production of an elaborate animal display.

Peripheral nerve reconstruction with epsilon-caprolactone conduits seeded with vasoactive intestinal peptide gene-transfected mesenchymal stem cells in a rat model

NASA Astrophysics Data System (ADS)

Hernández-Cortés, P.; Toledo-Romero, M. A.; Delgado, M.; Sánchez-González, C. E.; Martin, F.; Galindo-Moreno, P.; O'Valle, F.

2014-08-01

Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of a vasoactive intestinal peptide (VIP), a neuropeptide with neuroprotective, trophic and developmental regulatory actions, in peripheral nerve regeneration in a severe model of nerve injury that was repaired with nerve conduits. Approach. The sciatic nerve of each male Wistar rat was transected unilaterally at 10 mm and then repaired with Dl-lactic-ɛ-caprolactone conduits. The rats were treated locally with saline, with the VIP, with adipose-derived mesenchymal stem cells (ASCs) or with ASCs that were transduced with the VIP-expressing lentivirus. The rats with the transected nerve, with no repairs, were used as untreated controls. At 12 weeks post-surgery, we assessed their limb function by measuring the ankle stance angle and the percentage of their muscle mass reduction, and we evaluated the histopathology, immunohistochemistry and morphometry of the myelinated fibers. Main results. The rats that received a single injection of VIP-expressing ASCs showed a significant functional recovery in the ankle stance angle (p = 0.049) and a higher number of myelinated fibers in the middle and distal segments of the operated nerve versus the other groups (p = 0.046). Significance. These results suggest that utilization of a cellular substrate, plus a VIP source, is a promising method for enhancing nerve regeneration using Dl-lactic-ɛ-caprolactone conduits and that this method represents a potential useful clinical approach to repairing peripheral nerve damage.

Creating Interactions between Tissue-Engineered Skeletal Muscle and the Peripheral Nervous System.

PubMed

Smith, Alec S T; Passey, Samantha L; Martin, Neil R W; Player, Darren J; Mudera, Vivek; Greensmith, Linda; Lewis, Mark P

2016-01-01

Effective models of mammalian tissues must allow and encourage physiologically (mimetic) correct interactions between co-cultured cell types in order to produce culture microenvironments as similar as possible to those that would normally occur in vivo. In the case of skeletal muscle, the development of such a culture model, integrating multiple relevant cell types within a biomimetic scaffold, would be of significant benefit for investigations into the development, functional performance, and pathophysiology of skeletal muscle tissue. Although some work has been published regarding the behaviour of in vitro muscle models co-cultured with organotypic slices of CNS tissue or with stem cell-derived neurospheres, little investigation has so far been made regarding the potential to maintain isolated motor neurons within a 3D biomimetic skeletal muscle culture platform. Here, we review the current state of the art for engineering neuromuscular contacts in vitro and provide original data detailing the development of a 3D collagen-based model for the co-culture of primary muscle cells and motor neurons. The devised culture system promotes increased myoblast differentiation, forming arrays of parallel, aligned myotubes on which areas of nerve-muscle contact can be detected by immunostaining for pre- and post-synaptic proteins. Quantitative RT-PCR results indicate that motor neuron presence has a positive effect on myotube maturation, suggesting neural incorporation influences muscle development and maturation in vitro. The importance of this work is discussed in relation to other published neuromuscular co-culture platforms along with possible future directions for the field. © 2016 S. Karger AG, Basel.

Investigating the Effects of Peripheral Electrical Stimulation on Corticomuscular Functional Connectivity Stroke Survivors.

PubMed

Lai, Meei-I; Pan, Li-Ling; Tsai, Mei-Wun; Shih, Yi-Fen; Wei, Shun-Hwa; Chou, Li-Wei

2016-06-01

Electrical stimulation (ES) in the periphery can induce brain plasticity and has been used clinically to promote motor recovery in patients with central nervous system lesion. Electroencephalogram (EEG) and electromyogram (EMG) are readily applicable in clinical settings and can detect real-time functional connectivity between motor cortex and muscles with EEG-EMG (corticomuscular) coherence. The purpose of this study was to determine whether EEG-EMG coherence can detect changes in corticomuscular control induced by peripheral ES. Fifteen healthy young adults and 15 stroke survivors received 40-min electrical stimulation session on median nerve. The stimulation (1-ms rectangular pulse, 100 Hz) was delivered with a 20-s on-20-s off cycle, and the intensity was set at the subjects' highest tolerable level without muscle contraction or pain. Both before and after the stimulation session, subjects performed a 20-s steady-hold thumb flexion at 50% maximal voluntary contraction (MVC) while EEG and EMG were collected. Our results demonstrated that after ES, EEG-EMG coherence in gamma band increased significantly for 22.1 and 48.6% in healthy adults and stroke survivors, respectively. In addition, after ES, force steadiness was also improved in both groups, as indicated by the decrease in force fluctuation during steady-hold contraction (-1.7% MVC and -3.9%MVC for healthy and stroke individuals, respectively). Our results demonstrated that EEG-EMG coherence can detect ES-induced changes in the neuromuscular system. Also, because gamma coherence is linked to afferent inputs encoding, improvement in motor performance is likely related to ES-elicited strong sensory input and enhanced sensorimotor integration.

Central and peripheral fatigue development in the shoulder muscle with obesity during an isometric endurance task.

PubMed

Pajoutan, Mojdeh; Ghesmaty Sangachin, Mahboobeh; Cavuoto, Lora A

2017-07-21

Fatigue increases the likelihood of developing work-related musculoskeletal disorders and injury. Due to the physiological and neuromuscular changes that accompany obesity, it may alter the fatigue development mechanism and exacerbate injury risk. The upper extremities have the highest incidence rates for work-related musculoskeletal disorders. Therefore, the goals of this study were to investigate the effect of obesity on central vs. peripheral fatigue as well as on the physical signs of fatigue on the middle deltoid muscle. A measure of central activation ratio was used to quantify central fatigue by considering the increment in the torque output by superimposed twitch relative to its corresponding maximum voluntary contraction. For this purpose, electrical stimulation was delivered at the middle deltoid muscles of 22 non-obese (18 < body mass index (BMI) < 25 kg/m 2 ) and 17 obese (30 < BMI < 40 kg/m 2 ) individuals aged 18-32 years old. Participants completed superimposed maximum voluntary isometric contractions of shoulder abduction before and after a sustained isometric fatiguing task at either 30 or 60% of the muscle capacity. Differences in endurance time, torque fluctuation, torque loss, and muscle activity measured by an electromyography sensor were also investigated. A greater reduction of voluntary activation of motor units (p = 0.001) with fatigue was observed for individuals who are obese. Contrary to the effect of obesity on central fatigue, a trend toward reduced peripheral fatigue (p = 0.06) was observed for the obese group compared to the non-obese group. On average, a 14% higher rate of torque loss per second was observed among individuals with obesity in comparison to non-obese participants. The observed greater contribution of central fatigue during the sustained endurance tasks suggests that among young healthy obese individuals, the faster fatigue development with obesity, commonly reported in the literature, is most likely due to the central elements rather than the peripheral factors. This finding has implications for fatigue prevention programs during sustained exertions and can help to develop training, work, and rest schedules considering obesity.

Peripheral polyneuropathy after bariatric surgery for morbid obesity

PubMed Central

Lin, I-Ching; Lin, Ying-Li

2011-01-01

A patient with peripheral polyneuropathy after bariatric surgery for morbid obesity is reported. She suffered from frequent episodes of vomiting and abdominal pain after surgery. Muscle weakness in her lower limbs developed 5 months later and she experienced difficulty in walking and standing. Wrist drop, foot drop, and marked distal limb muscle atrophy were found bilaterally. Electromyography showed the presence of sensorimotor axonal polyneuropathy. Nutritional deficiencies may play an important role in pathogenesis. This uncommon neurological complication might be due to rapid weight loss and vitamin deficiency. Physicians who take care for patients after bariatric surgery should have a high index of awareness for the neurologic complications, and routine vitamin supplementation might be useful for these patients. PMID:22175046

Effects of preoperative oral carbohydrates and peptides on postoperative endocrine response, mobilization, nutrition and muscle function in abdominal surgery.

PubMed

Henriksen, M G; Hessov, I; Dela, F; Hansen, H Vind; Haraldsted, V; Rodt, S A

2003-02-01

Surgery is succeeded by long-lasting state of relative peripheral insulin resistance, which is reduced by giving glucose infusion or oral carbohydrate-rich drinks immediate before operating instead of fasting. The aim of the present study was to investigate whether oral carbohydrate or carbohydrate with peptide drinks preoperatively instead of fasting would improve postoperative voluntary muscle strength, nutritional intake and ambulation, decrease postoperative fatigue, anxiety and discomfort, and reduce the endocrine response to surgery. Forty-eight patients were included and randomized into three groups to receive 2 x 400 ml of carbohydrate-rich drinks or to fast overnight and allowed only water. Voluntary grip and quadriceps strength, body composition, pulmonary function, VAS-score of eight parameters of wellbeing, muscle biopsies and insulin, glucagon, IGF-1 and free fatty acids were measured before and after the operation. The basic postoperative regimen for all groups were immediate oral nutrition and early enforced mobilization. Significant postoperative decrease in glycogen synthase activity in the muscle biopsies was reduced in the intervention groups, and in combination, the intervention groups had a less reduced quadriceps strength after one week (-10% vs. -16%, NS) and one month (-5% vs. -13%, P < 0.05). Minor changes in the endocrine response to surgery were found without differences between the groups, and there were no differences between the groups in ambulation time, nutritional intake or subjective measures of wellbeing. Copyright Acta Anaesthesiologica Scandinavica 47 (2003)

Leptin resistance and diet-induced obesity: central and peripheral actions of leptin.

PubMed

Sáinz, Neira; Barrenetxe, Jaione; Moreno-Aliaga, María J; Martínez, José Alfredo

2015-01-01

Obesity is a chronic disease that represents one of the most serious global health burdens associated to an excess of body fat resulting from an imbalance between energy intake and expenditure, which is regulated by environmental and genetic interactions. The adipose-derived hormone leptin acts via a specific receptor in the brain to regulate energy balance and body weight, although this protein can also elicit a myriad of actions in peripheral tissues. Obese individuals, rather than be leptin deficient, have in most cases, high levels of circulating leptin. The failure of these high levels to control body weight suggests the presence of a resistance process to the hormone that could be partly responsible of disturbances on body weight regulation. Furthermore, leptin resistance can impair physiological peripheral functions of leptin such as lipid and carbohydrate metabolism and nutrient intestinal utilization. The present document summarizes those findings regarding leptin resistance development and the role of this hormone in the development and maintenance of an obese state. Thus, we focused on the effect of the impaired leptin action on adipose tissue, liver, skeletal muscle and intestinal function and the accompanying relationships with diet-induced obesity. The involvement of some inflammatory mediators implicated in the development of obesity and their roles in leptin resistance development are also discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

New synthetic prosthesis for peripheral nerve injuries: an experimental pilot study.

PubMed

Uranüs, Selman; Bretthauer, Georg; Nagele-Moser, Doris; Saliba, Sarah; Tomasch, Gordana; Rafolt, Dietmar; Justich, Ivo; Waldert, Jörg; Berghold, Andrea; Kleinert, Reinhold; Becker, Heinz; Voges, Udo; Wiederstein-Grasser, Iris; Koch, Horst

2013-04-01

Even the most modern technology has failed to induce satisfactory functional regeneration of traumatically severed peripheral nerves. Delayed neural regeneration and in consequence, slower neural conduction seriously limit muscle function in the area supplied by the injured nerve. This study aimed to compare a new nerve coaptation system involving an innovative prosthesis with the classical clinical method of sutured nerve coaptation. Besides the time and degree of nerve regeneration, the influence of electrostimulation was also tested. The sciatic nerve was severed in 14 female Göttingen minipigs with an average weight of 40.4 kg. The animals were randomized into 2 groups: One group received the new prosthesis and the other underwent microsurgical coaptation. In each group, according to the randomization a part of the animals received postoperative electrostimulation. Postoperative monitoring and the stimulation schedule covered a period of 9 months, during which axonal budding was evaluated monthly. The data from the pilot study indicate that results with the nerve prosthesis were comparable with those of conventional coaptation. The results indicate that implantation of the nerve prosthesis allows for good and effective neural regeneration. This new and simple treatment option for peripheral nerve injuries can be performed in any hospital with surgical facilities as it does not involve the demanding microsurgical suture technique that can only be performed in specialized centers.

Transcranial magnetic stimulation of the human brain: responses in muscles supplied by cranial nerves.

PubMed

Benecke, R; Meyer, B U; Schönle, P; Conrad, B

1988-01-01

The present investigation demonstrates that time-varying magnetic fields induced over the skull elicit distinct types of responses in muscles supplied by the cranial nerves both on the ipsilateral and the contralateral side. When the center of the copper coil was positioned 4 cm lateral to the vertex on a line from the vertex to the external auditory meatus, bilateral responses in the masseter, orbicularis oculi, mentalis, and sternocleidomastoideus muscles with a delay of about 10 to 14 ms after the stimulus occurred. Similar to the transcranially evoked muscle responses in hand muscles, the responses in the cranial muscles can be influenced in latency and amplitude by background excitation. It is concluded that these responses are induced by excitation of the face-associated motor cortex followed by multiple I-waves in the corticonuclear tract with both ipsilateral and contralateral projections to the corresponding motoneurones. Additionally, at higher stimulation strengths "short-latency" ipsilateral responses in muscles supplied by the trigeminal, facial, and accessory nerves occurred which we suggest are induced by direct stimulation of the peripheral cranial nerves in their intracisternal course. The present study confirms the bilateral projection of corticonuclear tracts in awake unanesthetised human subjects which has been observed by electrical stimulation on the exposed cortex during surgical procedures already decades ago. The present investigation will serve as a basis for the assessment of pathophysiological mechanisms involving the corticonuclear system or the peripheral cranial nerves in their proximal parts in awake humans.

Complex regional pain syndrome type I (RSD): pathology of skeletal muscle and peripheral nerve.

PubMed

van der Laan, L; ter Laak, H J; Gabreëls-Festen, A; Gabreëls, F; Goris, R J

1998-07-01

Reflex sympathetic dystrophy (RSD) (recently reclassified as complex regional pain syndrome type I) is a syndrome occurring in extremities and, when chronic, results in severe disability and untractable pain. RSD may be accompanied by neurologic symptoms even when there is no previous neurologic lesion. There is no consensus as to the pathogenic mechanism involved in RSD. To gain insight into the pathophysiology of RSD, we studied histopathology of skeletal muscle and peripheral nerve from patients with chronic RSD in a lower extremity. In eight patients with chronic RSD, an above-the-knee amputation was performed because of a nonfunctional limb. Specimens of sural nerves, tibial nerves, common peroneal nerves, gastrocnemius muscles, and soleus muscles were obtained from the amputated legs and analyzed by light and electron microscopy. In all patients, the affected leg showed similar neurologic symptoms such as spontaneous pain, hyperpathy, allodynia, paresis, and anesthesia dolorosa. The nerves showed no consistent abnormalities of myelinated fibers. In four patients, the C-fibers showed electron microscopic pathology. In all patients, the gastrocnemius and soleus muscle specimens showed a decrease of type I fibers, an increase of lipofuscin pigment, atrophic fibers, and severely thickened basal membrane layers of the capillaries. In chronic RSD, efferent nerve fibers were histologically unaffected; from afferent fibers, only C-fibers showed histopathologic abnormalities. Skeletal muscle showed a variety of histopathologic findings, which are similar to the histologic abnormalities found in muscles of patients with diabetes.

Enhancing Peripheral Nerve Regeneration with a Novel Drug Delivering Nerve Conduit

DTIC Science & Technology

2017-12-01

control group ) or a conduit that released GDNF. The main outcome measures were muscle atrophy, electrophysiology, motor endplate reinnervation...prepared NGF+GDNF ( Control groups ). 8 Gastrocnemius Atrophy The gastrocnemius muscle weight of the GDNF treated group was ~ 60% of the non...experimental side at 10 weeks. GDNF conduit group (49.4±1.4 %) had statistically less muscle atrophy than the control group (65.1±5.1 %) (pɘ.05) at 10

Pharmacologic and Nonpharmacologic Approaches to the Treatment of Hypertension with Implications for the Clinical Nurse Specialist

DTIC Science & Technology

1988-01-01

Hypertension 6 14 that assist in regulation of smooth muscle contraction . This results in a lowered peripheral vascular resistance and 6 thus, a lowering of...the effect of epinephrine and also allows the sustained vascular smooth - muscle contraction caused by the catecholamines; this too, contributing to an...hypertension. These agents cause arteriolar dilatation by acting directly on vascular smooth muscle . They do this by interfering with the calcium gates

Regional peripheral and CNS hemodynamic effects of intrathecal administration of a substance P receptor agonist.

PubMed

Helke, C J; Phillips, E T; O'Neill, J T

1987-11-01

Regional CNS and peripheral hemodynamic effects of the intrathecal (i.t.) administration of a substance P receptor agonist, [pGlu5,MePhe8,MeGly9]-substance P5-11 ([DiMe]-SP), were studied in anesthetized rats with the radioactive microsphere technique. It was previously shown that [DiMe]-SP caused a sympathetically mediated increase in mean arterial pressure (MAP) by an action within the spinal cord. In this study, [DiMe]-SP (5 and 33 nmol, i.t.) increased MAP. The 5 nmol dose increased resistance in cutaneous, renal, splanchnic, and adrenal vascular beds but decreased resistance, and increased blood flow in some skeletal muscle beds. Total peripheral resistance was unchanged. The 33 nmol dose increased resistance in each peripheral vascular bed analyzed and increased total peripheral resistance. Whereas each dose increased heart rate, stroke volume and cardiac output were unchanged with the 5 nmol dose and were reduced with the 33 nmol dose. Neither dose of [DiMe]-SP significantly altered regional brain or spinal cord blood flows. These data show that the i.t. administration of the SP agonist, [DiMe]-SP, increased vascular tone to most peripheral vascular beds whereas the low dose caused a vasodilation of skeletal muscle. These effects are consistent with the notion of a dose-related activation of SP receptors in the spinal cord affecting sympathetic outflow to the adrenals and to the vasculature.

Etiology and Recovery of Neuromuscular Fatigue following Competitive Soccer Match-Play

PubMed Central

Brownstein, Callum G.; Dent, Jack P.; Parker, Paul; Hicks, Kirsty M.; Howatson, Glyn; Goodall, Stuart; Thomas, Kevin

2017-01-01

Aim: Previous research into the etiology of neuromuscular fatigue following competitive soccer match-play has primarily focused on peripheral perturbations, with limited research assessing central nervous system function in the days post-match. The aim of the present study was to examine the contribution and time-course of recovery of central and peripheral factors toward neuromuscular fatigue following competitive soccer match-play. Methods: Sixteen male semi-professional soccer players completed a 90-min soccer match. Pre-, post- and at 24, 48, and 72 h participants completed a battery of neuromuscular, physical, and perceptual tests. Maximal voluntary contraction force (MVC) and twitch responses to electrical (femoral nerve) and transcranial magnetic stimulation (TMS) of the motor cortex during isometric knee-extension and at rest were measured to assess central nervous system (voluntary activation, VA) and muscle contractile (potentiated twitch force, Qtw, pot) function. Electromyography responses of the rectus femoris to single- and paired-pulse TMS were used to assess corticospinal excitability and short-interval intracortical inhibition (SICI), respectively. Fatigue and perceptions of muscle soreness were assessed via visual analog scales, and physical function was assessed through measures of jump (countermovement jump height and reactive strength index) and sprint performance. Results: Competitive match-play elicited significant post-match declines in MVC force (−14%, P < 0.001) that persisted for 48 h (−4%, P = 0.01), before recovering by 72 h post-exercise. VA (motor point stimulation) was reduced immediately post-match (−8%, P < 0.001), and remained depressed at 24 h (−5%, P = 0.01) before recovering by 48 h post-exercise. Qtw,pot was reduced post-match (−14%, P < 0.001), remained depressed at 24 h (−6%, P = 0.01), before recovering by 48 h post-exercise. No changes were evident in corticospinal excitability or SICI. Jump performance took 48 h to recover, while perceptions of fatigue persisted at 72 h. Conclusion: Competitive soccer match-play elicits substantial impairments in central nervous system and muscle function, requiring up to 48 h to resolve. The results of the study could have important implications for fixture scheduling, the optimal management of the training process, squad rotation during congested competitive schedules, and the implementation of appropriate recovery interventions. PMID:29118716

Effects of exercise training on brain-derived neurotrophic factor in skeletal muscle and heart of rats post myocardial infarction.

PubMed

Lee, Heow Won; Ahmad, Monir; Wang, Hong-Wei; Leenen, Frans H H

2017-03-01

What is the central question of this study? Exercise training increases brain-derived neurotrophic factor (BDNF) in the hippocampus, which depends on a myokine, fibronectin type III domain-containing protein 5 (FNDC5). Whether exercise training after myocardial infarction induces parallel increases in FNDC5 and BDNF expression in skeletal muscle and the heart has not yet been studied. What is the main finding and its importance? Exercise training after myocardial infarction increases BDNF protein in skeletal muscle and the non-infarct area of the LV without changes in FNDC5 protein, suggesting that BDNF is not regulated by FNDC5 in skeletal muscle and heart. An increase in cardiac BDNF may contribute to the improvement of cardiac function by exercise training. Exercise training after myocardial infarction (MI) attenuates progressive left ventricular (LV) remodelling and dysfunction, but the peripheral stimuli induced by exercise that trigger these beneficial effects are still unclear. We investigated as possible mediators fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF) in the skeletal muscle and heart. Male Wistar rats underwent either sham surgery or ligation of the left descending coronary artery, and surviving MI rats were allocated to either a sedentary (Sed-MI) or an exercise group (ExT-MI). Exercise training was done for 4 weeks on a motor-driven treadmill. At the end, LV function was evaluated, and FNDC5 and BDNF mRNA and protein were assessed in soleus muscle, quadriceps and non-, peri- and infarct areas of the LV. At 5 weeks post MI, FNDC5 mRNA was decreased in soleus muscle and all areas of the LV, but FNDC5 protein was increased in the soleus muscle and the infarct area. Mature BDNF (mBDNF) protein was decreased in the infarct area without a change in mRNA. Exercise training attenuated the decrease in ejection fraction and the increase in LV end-diastolic pressure post MI. Exercise training had no effect on FNDC5 mRNA and protein, but increased mBDNF protein in soleus muscle, quadriceps and the non-infarct area of the LV. The mBDNF protein in the non-infarct area correlated positively with ejection fraction and inversely with LV end-diastolic pressure. In conclusion, mBDNF is induced by exercise training in skeletal muscle and the non-infarct area of the LV, which may contribute to improvement of muscle dysfunction and cardiac function post MI. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability.

PubMed

Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

2017-01-01

Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 ( n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 ( n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability.

Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability

PubMed Central

Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

2017-01-01

Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 (n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 (n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability. PMID:28392766

Is ability to hepatic steatosis influenced by age at the beginning of the overfeeding period in Muscovy and Pekin ducks?

PubMed

Chartrin, P; Bernadet, M D; Sannier, M; Baéza, E

2013-04-01

The aim of this study was to analyse the effects of species (Muscovy and Pekin ducks) and age at the beginning of the overfeeding period on fatty liver production, carcass composition and lipid and moisture content of the liver and breast muscle. We reared four groups of 40 ducks per species for the study, starting at 2-week intervals in order to have four different ages together at the beginning of the overfeeding period (10, 12, 14 and 16 weeks). At the end of the overfeeding period, all ducks were slaughtered. Our results confirmed the high levels of difference in carcass composition and lipid content in the plasma, liver and breast muscle between Muscovy and Pekin ducks at all ages. Pekin ducks were not able to develop a high degree of hepatic steatosis, but had increased lipid storage in peripheral adipose and muscle tissues than Muscovy ducks. However, the fatty liver weight of Pekin ducks increased with age, with lipid deposition in the liver and peripheral tissues. The ability of Muscovy ducks to produce fatty livers remained unchanged with age in line, with lipid deposition in the liver and peripheral tissues. The sites of lipid deposition thus depend on species and not on the physiological maturity of ducks.

Resistance Training using Low Cost Elastic Tubing is Equally Effective to Conventional Weight Machines in Middle-Aged to Older Healthy Adults: A Quasi-Randomized Controlled Clinical Trial

PubMed Central

Lima, Fabiano F.; Camillo, Carlos A.; Gobbo, Luis A.; Trevisan, Iara B.; Nascimento, Wesley B. B. M.; Silva, Bruna S. A.; Lima, Manoel C. S.; Ramos, Dionei; Ramos, Ercy M. C.

2018-01-01

The objectives of the study were to compare the effects of resistance training using either a low cost and portable elastic tubing or conventional weight machines on muscle force, functional exercise capacity, and health-related quality of life (HRQOL) in middle-aged to older healthy adults. In this clinical trial twenty-nine middle-aged to older healthy adults were randomly assigned to one of the three groups a priori defined: resistance training with elastic tubing (ETG; n = 10), conventional resistance training (weight machines) (CTG; n = 9) and control group (CG, n = 10). Both ETG and CTG followed a 12-week resistance training (3x/week - upper and lower limbs). Muscle force, functional exercise capacity and HRQOL were evaluated at baseline, 6 and 12 weeks. CG underwent the three evaluations with no formal intervention or activity counseling provided. ETG and CTG increased similarly and significantly muscle force (Δ16-44% in ETG and Δ25-46% in CTG, p < 0.05 for both), functional exercise capacity (ETG Δ4 ± 4% and CTG Δ6±8%; p < 0.05 for both). Improvement on “pain” domain of HRQOL could only be observed in the CTG (Δ21 ± 26% p = 0.037). CG showed no statistical improvement in any of the variables investigated. Resistance training using elastic tubing (a low cost and portable tool) and conventional resistance training using weight machines promoted similar positive effects on peripheral muscle force and functional exercise capacity in middle-aged to older healthy adults. Key points There is compeling evidence linking resistance training to health. Elastic resistance training improves the functionality of middle-aged to older healthy adults. Elastic resistance training was shown to be as effective as conventional resistence training in middle-aged to older healthy adults. PMID:29535589

Central and peripheral cardiovascular responses to electrically induced and voluntary leg exercise

NASA Technical Reports Server (NTRS)

Saltin, B.; Strange, S.; Bangsbo, J.; Kim, C. K.; Duvoisin, M.; Hargens, A.; Gollnick, P. D.

1990-01-01

With long missions in space countermeasures have to be used to secure safe operations in space and a safe return to Earth. Exercises of various forms have been used, but the question has arisen whether electrically induced contractions of muscle especially sensitive to weightlessness and crucial for man's performance would aid in maintaining their optimal function. The physiological responses both to short term and prolonged dynamic exercise performed either voluntarily or induced by electrical stimulation were considered. The local and systemic circulatory responses were similar for the voluntary and electrically induced contractions. The metabolic response was slightly more pronounced with electrical stimulation. This could be a reflection of not only slow twitch (type 1) but also fast twitch (type 2) fibers being recruited when the contractions were induced electrically. Intramuscular pressure recordings indicated that the dominant fraction of the muscle group was engaged regardless of mode of activation. Some 70 percent of the short term peak voluntary exercise capacity could be attained with electrical stimulation. Thus, electrically induced contractions of specific muscle groups should indeed be considered as an efficient countermeasure.

The Botulinum Toxin as a Therapeutic Agent: Molecular Structure and Mechanism of Action in Motor and Sensory Systems.

PubMed

Kumar, Raj; Dhaliwal, Harkiran Preet; Kukreja, Roshan Vijay; Singh, Bal Ram

2016-02-01

Botulinum neurotoxin (BoNT) produced by Clostridium botulinum is the most potent molecule known to mankind. Higher potency of BoNT is attributed to several factors, including structural and functional uniqueness, target specificity, and longevity. Although BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity. Weakening of muscles due to peripheral action of BoNT produces a therapeutic effect. Depending on the target tissue, BoNT can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. In recent observations of the analgesic properties of BoNT, the toxin modifies the sensory feedback loop to the central nervous system. Differential effects of BoNT in excitatory and inhibitory neurons provide a unique therapeutic tool. In this review the authors briefly summarize the structure and mechanism of actions of BoNT on motor and sensory neurons to explain its therapeutic effects and future potential. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Feedforward Compensation Mediated by the Central and Peripheral Actions of a Single Neuropeptide Discovered Using Representational Difference Analysis

PubMed Central

Jing, Jian; Sweedler, Jonathan V; Cropper, Elizabeth C; Alexeeva, Vera; Park, Ji-Ho; Romanova, Elena V.; Xie, Fang; Dembrow, Nikolai C.; Ludwar, Bjoern C.; Weiss, Klaudiusz R; Vilim, Ferdinand S

2010-01-01

Compensatory mechanisms are often used to achieve stability by reducing variance, which can be accomplished via negative feedback during homeostatic regulation. In principle, compensation can also be implemented through feedforward mechanisms where a regulator acts to offset the anticipated output variation; however, few such neural mechanisms have been demonstrated. We provide evidence that an Aplysia neuropeptide, identified using an enhanced representational difference analysis procedure, implements feedforward compensation within the feeding network. We named the novel peptide allatotropin-related peptide (ATRP) because of its similarity to insect allatotropin. Mass spectrometry confirmed the peptide's identity, and in situ hybridization and immunostaining mapped its distribution in the Aplysia CNS. ATRP is present in the higher-order cerebral-buccal interneuron (CBI), CBI-4, but not in CBI-2. Previous work showed that CBI-4-elicited motor programs have a shorter protraction duration than those elicited by CBI-2. Here we show that ATRP shortens protraction duration of CBI-2-elicited ingestive programs, suggesting a contribution of ATRP to the parametric differences between CBI-4- and CBI-2-evoked programs. Importantly, because Aplysia muscle contractions are a graded function of motoneuronal activity, one consequence of the shortening of protraction is that it can weaken protraction movements. However, this potential weakening is offset by feedforward compensatory actions exerted by ATRP. Centrally, ATRP increases the activity of protraction motoneurons. Moreover, ATRP is present in peripheral varicosities of protraction motoneurons and enhances peripheral motoneuron-elicited protraction muscle contractions. Therefore, feedforward compensatory mechanisms mediated by ATRP make it possible to generate a faster movement with an amplitude that is not greatly reduced, thereby producing stability. PMID:21147994

Intramyocellular Lipid Droplet Size Rather Than Total Lipid Content is Related to Insulin Sensitivity After 8 Weeks of Overfeeding.

PubMed

Covington, Jeffrey D; Johannsen, Darcy L; Coen, Paul M; Burk, David H; Obanda, Diana N; Ebenezer, Philip J; Tam, Charmaine S; Goodpaster, Bret H; Ravussin, Eric; Bajpeyi, Sudip

2017-12-01

Intramyocellular lipid (IMCL) is inversely related to insulin sensitivity in sedentary populations, yet no prospective studies in humans have examined IMCL accumulation with overfeeding. Twenty-nine males were overfed a high-fat diet (140% caloric intake, 44% from fat) for 8 weeks. Measures of IMCL, whole-body fat oxidation from a 24-hour metabolic chamber, muscle protein extracts, and muscle ceramide measures were obtained before and after the intervention. Eight weeks of overfeeding did not increase overall IMCL. The content of smaller lipid droplets peripherally located in the myofiber decreased, while increases in larger droplets correlated inversely with glucose disposal rate. Overfeeding resulted in inhibition of Akt activity, which correlated with the reductions in smaller, peripherally located lipid droplets and drastic increases in ceramide content. Additionally, peripherally located lipid droplets were associated with more efficient lipid oxidation. Finally, participants who maintained a greater number of smaller, peripherally located lipid droplets displayed a better resistance to weight gain with overfeeding. These results show that lipid droplet size and location rather than mere IMCL content are important to understanding insulin sensitivity. © 2017 The Obesity Society.

Extraneural findings during peripheral nerve ultrasound: Prevalence and further assessment.

PubMed

Bignotti, Bianca; Zaottini, Federico; Airaldi, Sonia; Martinoli, Carlo; Tagliafico, Alberto

2018-01-01

In this study we evaluated the frequency and further assessment of extraneural findings encountered during peripheral nerve ultrasound (US). Our retrospective review identified 278 peripheral nerve US examinations of 229 patients performed between December 2014 and December 2015. Reports were reviewed to assess the number of studies without peripheral nerve abnormalities and the frequency and further assessment of extraneural findings. A total of 107 peripheral nerve US examinations of 90 patients (49 men and 41 women, mean age 55 ± 16 years) did not report peripheral nerve abnormalities. Extraneural findings were observed in 24 of 107 (22.4%) studies. Fifteen of the 278 [5.4% (95% confidence interval 2.7%-8.1%)] studies led to a recommendation for additional imaging or clinical evaluation of an extraneural finding. At least 5.4% (15 of 278) of peripheral nerve US studies led to additional clinical or imaging assessment. Muscle Nerve 57: 65-69, 2018. © 2017 Wiley Periodicals, Inc.

Dairy food intake, peripheral bone structure, and muscle mass in elderly ambulatory women.

PubMed

Radavelli-Bagatini, Simone; Zhu, Kun; Lewis, Joshua R; Prince, Richard L

2014-07-01

Previous studies suggest that dairy intake may be associated with reduced bone and muscle loss with aging, but there are limited data in the very old. We evaluated the association between intake of dairy foods and peripheral bone structure and muscle mass in 564 elderly women aged 80 to 92 (mean 84.7) years, who were participants of the Calcium Intake Fracture Outcome Study/CAIFOS Aged Extension Study (CAIFOS/CARES) cohort and attended the 10-year follow-up. Assessments included dairy consumption (milk, yogurt, and cheese) by a validated food frequency questionnaire, 15% tibia bone mass, area and volumetric bone mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), and appendicular bone and skeletal muscle mass by dual-energy X-ray absorptiometry (DXA). Women were categorized according to tertiles of dairy intake: first tertile (≤ 1.5 servings/d), second tertile (1.5 to 2.2 servings/d) and third tertile (≥ 2.2 servings/d). Controlling for confounding factors, pQCT assessment at the 15% tibia showed that compared with those in the first tertile of dairy intake, women in the third tertile had 5.7% greater total bone mass (p = 0.005), principally because of an increase in cortical and subcortical bone mass (5.9%, p = 0.050), resulting in a 6.2% increase in total vBMD (p = 0.013). Trabecular but not cortical and subcortical vBMD was also higher (7.8%, p = 0.044). DXA assessment showed that women in the third tertile of dairy intake had greater appendicular bone mass (7.1%, p = 0.007) and skeletal muscle mass (3.3%, p = 0.014) compared with tertile 1. The associations with bone measures were dependent on dairy protein and calcium intakes, whereas the association with appendicular muscle mass was not totally dependent on dairy protein intake. Our results suggest a positive association of dairy intake with appendicular bone mineralization and muscle mass in elderly women. Because many fractures in this age group are of the appendicular skeleton often associated with falls, dairy intake may be a modifiable lifestyle factor contributing to healthy aging. © 2014 American Society for Bone and Mineral Research.

The chick embryo: a leading model in somitogenesis studies.

PubMed

Pourquié, Olivier

2004-09-01

The vertebrate body is built on a metameric organization which consists of a repetition of functionally equivalent units, each comprising a vertebra, its associated muscles, peripheral nerves and blood vessels. This periodic pattern is established during embryogenesis by the somitogenesis process. Somites are generated in a rhythmic fashion from the presomitic mesoderm and they subsequently differentiate to give rise to the vertebrae and skeletal muscles of the body. Somitogenesis has been very actively studied in the chick embryo since the 19th century and many of the landmark experiments that led to our current understanding of the vertebrate segmentation process have been performed in this organism. Somite formation involves an oscillator, the segmentation clock whose periodic signal is converted into the periodic array of somite boundaries by a spacing mechanism relying on a traveling threshold of FGF signaling regressing in concert with body axis extension.

Group III/IV muscle afferents limit the intramuscular metabolic perturbation during whole body exercise in humans

PubMed Central

Mangum, Tyler S.; Sidhu, Simranjit K.; Weavil, Joshua C.; Hureau, Thomas J.; Jessop, Jacob E.; Bledsoe, Amber D.; Richardson, Russell S.; Amann, Markus

2016-01-01

Key points The purpose of this study was to determine the role of group III/IV muscle afferents in limiting the endurance exercise‐induced metabolic perturbation assayed in muscle biopsy samples taken from locomotor muscle.Lumbar intrathecal fentanyl was used to attenuate the central projection of μ‐opioid receptor‐sensitive locomotor muscle afferents during a 5 km cycling time trial.The findings suggest that the central projection of group III/IV muscle afferent feedback constrains voluntary neural ‘drive’ to working locomotor muscle and limits the exercise‐induced intramuscular metabolic perturbation.Therefore, the CNS might regulate the degree of metabolic perturbation within locomotor muscle and thereby limit peripheral fatigue. It appears that the group III/IV muscle afferents are an important neural link in this regulatory mechanism, which probably serves to protect locomotor muscle from the potentially severe functional impairment as a consequence of severe intramuscular metabolic disturbance. Abstract To investigate the role of metabo‐ and mechanosensitive group III/IV muscle afferents in limiting the intramuscular metabolic perturbation during whole body endurance exercise, eight subjects performed 5 km cycling time trials under control conditions (CTRL) and with lumbar intrathecal fentanyl impairing lower limb muscle afferent feedback (FENT). Vastus lateralis muscle biopsies were obtained before and immediately after exercise. Motoneuronal output was estimated through vastus lateralis surface electromyography (EMG). Exercise‐induced changes in intramuscular metabolites were determined using liquid and gas chromatography‐mass spectrometry. Quadriceps fatigue was quantified by pre‐ to post‐exercise changes in potentiated quadriceps twitch torque (ΔQTsingle) evoked by electrical femoral nerve stimulation. Although motoneuronal output was 21 ± 12% higher during FENT compared to CTRL (P < 0.05), time to complete the time trial was similar (∼8.8 min). Compared to CTRL, power output during FENT was 10 ± 4% higher in the first half of the time trial, but 11 ± 5% lower in the second half (both P < 0.01). The exercise‐induced increase in intramuscular inorganic phosphate, H+, adenosine diphosphate, lactate and phosphocreatine depletion was 55 ± 30, 62 ± 18, 129 ± 63, 47 ± 14 (P < 0.001) and 27 ± 14% (P < 0.01) greater in FENT than CTRL. ΔQTsingle was greater following FENT than CTRL (−52 ± 2 vs −31 ± 1%, P < 0.001) and this difference was positively correlated with the difference in inorganic phosphate (r 2 = 0.79; P < 0.01) and H+ (r 2 = 0.92; P < 0.01). In conclusion, during whole body exercise, group III/IV muscle afferents provide feedback to the CNS which, in turn, constrains motoneuronal output to the active skeletal muscle. This regulatory mechanism limits the exercise‐induced intramuscular metabolic perturbation, preventing an abnormal homeostatic challenge and excessive peripheral fatigue. PMID:27241818

The effects of elastic tubing-based resistance training compared with conventional resistance training in patients with moderate chronic obstructive pulmonary disease: a randomized clinical trial.

PubMed

Ramos, Ercy Mara Cipulo; de Toledo-Arruda, Alessandra Choqueta; Fosco, Luciana Cristina; Bonfim, Rafaela; Bertolini, Giovana Navarro; Guarnier, Flavia Alessandra; Cecchini, Rubens; Pastre, Carlos Marcelo; Langer, Daniel; Gosselink, Rik; Ramos, Dionei

2014-11-01

To investigate the effects of elastic tubing training compared with conventional resistance training on the improvement of functional exercise capacity, muscle strength, fat-free mass, and systemic inflammation in patients with chronic obstructive pulmonary disease. A prospective, randomized, eight-week clinical trial. The study was conducted in a university-based, outpatient, physical therapy clinic. A total of 49 patients with moderate chronic obstructive pulmonary disease. Participants were randomly assigned to perform elastic tubing training or conventional resistance training three times per week for eight weeks. The primary outcome measure was functional exercise capacity. The secondary outcome measures were peripheral muscle strength, health-related quality of life assessed by the Chronic Respiratory Disease Questionnaire (CRDQ), fat-free mass, and cytokine profile. After eight weeks, the mean distance covered during six minutes increased by 73 meters (±69) in the elastic tubing group and by 42 meters (±59) in the conventional group (p < 0.05). The muscle strength and quality of life improved in both groups (P < 0.05), with no significant differences between the groups. There was a trend toward an improved fat-free mass in both groups (P = 0.05). After the first and last sessions, there was an increase in interleukin 1β (IL-1β) and interleukin 10 (IL-10) in both groups, while tumour necrosis factor alpha (TNF-α) was stimulated only in the conventional training group. Elastic tubing training had a greater effect on functional exercise capacity than conventional resistance training. Both interventions were equally effective in improving muscle strength and quality of life. © The Author(s) 2014.

The fate of neurotization techniques on reinnervation after denervation of the gastrocnemius muscle: an experimental study.

PubMed

Askar, I; Sabuncuoglu, B T; Yormuk, E; Saray, A

2001-07-01

In nerve injuries, if it is not possible to reinnervate muscle by using neurorrhaphy and nerve grafting technique, reinnervation should be provided by the use of neuroization-directly implanting motor nerve into muscle. A comparative study of three techniques of neurotization is presented in rabbits. In this experimental study, a total of 40 white New Zealand rabbits were used and divided into four groups, each including 10 rabbits. In the first group (control--Group 1), only surgical exposure of the gastrocnemius muscle, main muscle nerve (tibial nerve), and peroneal nerve was done, without any injury to the nerves. In the second group (direct neurotization group--Group 2), the tibial nerve was transected, and the peroneal nerve, which had already been divided into fascicles, was implanted into the lateral head of the gastrocnemius muscle aneural zone. In the third group (dual neurotization group--Group 3), the tibial nerve which had been transected and re-anastomosed, and the peroneal nerve were implanted into the lateral head of the gastrocnemius muscle. In the last experimental group (hyperneurotization group--Group 4), fascicles of the peroneal nerve were implanted into the lateral head of the gastrocnemius, preserving the tibial nerve. Six months later, changes in the histologic pattern and the functional recovery of the gastrocnemius muscle were investigated. It was found that functional recovery was achieved in all neurotization groups. Groups with the tibial nerve transected had less muscular weights than those of groups with the tibial nerve intact. EMG recordings showed that polyphasic and late potentials were frequently seen in groups with the tibial nerve transected. Degeneration and regeneration of myofibrils was observed in such groups as well. New motor end-plates, including vesicles, were formed in a scattered manner in all neurotization groups. As a result, the authors conclude that direct and dual neurotization techniques are useful in peripheral nerve injuries, if it is not possible to reinnervate muscle by using neurorraphy and nerve grafting, and that there is no suggested superiority among these techniques.

Dietary nitrate supplementation: impact on skeletal muscle vascular control in exercising rats with chronic heart failure

PubMed Central

Ferguson, Scott K.; Holdsworth, Clark T.; Colburn, Trenton D.; Wright, Jennifer L.; Craig, Jesse C.; Fees, Alex; Jones, Andrew M.; Allen, Jason D.; Musch, Timothy I.

2016-01-01

Chronic heart failure (CHF) results in central and peripheral derangements that ultimately reduce skeletal muscle O2 delivery and impair exercise tolerance. Dietary nitrate (NO3−) supplementation improves skeletal muscle vascular function and tolerance to exercise. We tested the hypothesis that NO3− supplementation would elevate exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats. Myocardial infarction (MI) was induced (coronary artery ligation) in young adult male rats. After 21 days of recovery, rats randomly received 5 days of NO3−-rich beetroot juice (CHF + BR, n = 10) or a placebo (CHF, n = 10). Mean arterial pressure (carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% grade). CHF-induced dysfunction, as determined by myocardial infarction size (29 ± 3% and 33 ± 4% in CHF and CHF + BR, respectively) and left ventricular end-diastolic pressure (18 ± 2 and 18 ± 2 mmHg in CHF and CHF + BR, respectively), and exercising mean arterial pressure (131 ± 3 and 128 ± 4 mmHg in CHF and CHF + BR, respectively) were not different (P > 0.05) between groups. Total exercising hindlimb skeletal muscle BF (95 ± 5 and 116 ± 9 ml·min−1·100 g−1 in CHF and CHF + BR, respectively) and VC (0.75 ± 0.05 and 0.90 ± 0.05 ml·min−1·100 g−1·mmHg−1 in CHF and CHF + BR, respectively) were 22% and 20% greater in BR-supplemented rats, respectively (P < 0.05). During exercise, BF in 9 and VC in 10 hindlimb muscles and muscle portions were significantly greater in the CHF + BR group. These results provide strong evidence that dietary NO3− supplementation improves skeletal muscle vascular function during exercise in rats with CHF and, thus, support the use of BR as a novel therapeutic modality for the treatment of CHF. PMID:27445296

Dietary nitrate supplementation: impact on skeletal muscle vascular control in exercising rats with chronic heart failure.

PubMed

Ferguson, Scott K; Holdsworth, Clark T; Colburn, Trenton D; Wright, Jennifer L; Craig, Jesse C; Fees, Alex; Jones, Andrew M; Allen, Jason D; Musch, Timothy I; Poole, David C

2016-09-01

Chronic heart failure (CHF) results in central and peripheral derangements that ultimately reduce skeletal muscle O2 delivery and impair exercise tolerance. Dietary nitrate (NO3 (-)) supplementation improves skeletal muscle vascular function and tolerance to exercise. We tested the hypothesis that NO3 (-) supplementation would elevate exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats. Myocardial infarction (MI) was induced (coronary artery ligation) in young adult male rats. After 21 days of recovery, rats randomly received 5 days of NO3 (-)-rich beetroot juice (CHF + BR, n = 10) or a placebo (CHF, n = 10). Mean arterial pressure (carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% grade). CHF-induced dysfunction, as determined by myocardial infarction size (29 ± 3% and 33 ± 4% in CHF and CHF + BR, respectively) and left ventricular end-diastolic pressure (18 ± 2 and 18 ± 2 mmHg in CHF and CHF + BR, respectively), and exercising mean arterial pressure (131 ± 3 and 128 ± 4 mmHg in CHF and CHF + BR, respectively) were not different (P > 0.05) between groups. Total exercising hindlimb skeletal muscle BF (95 ± 5 and 116 ± 9 ml·min(-1)·100 g(-1) in CHF and CHF + BR, respectively) and VC (0.75 ± 0.05 and 0.90 ± 0.05 ml·min(-1)·100 g(-1)·mmHg(-1) in CHF and CHF + BR, respectively) were 22% and 20% greater in BR-supplemented rats, respectively (P < 0.05). During exercise, BF in 9 and VC in 10 hindlimb muscles and muscle portions were significantly greater in the CHF + BR group. These results provide strong evidence that dietary NO3 (-) supplementation improves skeletal muscle vascular function during exercise in rats with CHF and, thus, support the use of BR as a novel therapeutic modality for the treatment of CHF. Copyright © 2016 the American Physiological Society.

A comparison of peripheral imaging technologies for bone and muscle quantification: a technical review of image acquisition

PubMed Central

Wong, A.K.O.

2016-01-01

The choice of an appropriate imaging technique to quantify bone, muscle, or muscle adiposity needs to be guided by a thorough understanding of its competitive advantages over other modalities balanced by its limitations. This review details the technical machinery and methods behind peripheral quantitative computed tomography (pQCT), high-resolution (HR)-pQCT, and magnetic resonance imaging (MRI) that drive successful depiction of bone and muscle morphometry, densitometry, and structure. It discusses a number of image acquisition settings, the challenges associated with using one versus another, and compares the risk-benefits across the different modalities. Issues related to all modalities including partial volume artifact, beam hardening, calibration, and motion assessment are also detailed. The review further provides data and images to illustrate differences between methods to better guide the reader in selecting an imaging method strategically. Overall, investigators should be cautious of the impact of imaging parameters on image signal or contrast-to-noise-ratios, and the need to report these settings in future publications. The effect of motion should be assessed on images and a decision made to exclude prior to segmentation. A more standardized approach to imaging bone and muscle on pQCT and MRI could enhance comparability across studies and could improve the quality of meta-analyses. PMID:27973379

A comparison of peripheral imaging technologies for bone and muscle quantification: a technical review of image acquisition.

PubMed

Wong, A K

2016-12-14

The choice of an appropriate imaging technique to quantify bone, muscle, or muscle adiposity needs to be guided by a thorough understanding of its competitive advantages over other modalities balanced by its limitations. This review details the technical machinery and methods behind peripheral quantitative computed tomography (pQCT), high-resolution (HR)-pQCT, and magnetic resonance imaging (MRI) that drive successful depiction of bone and muscle morphometry, densitometry, and structure. It discusses a number of image acquisition settings, the challenges associated with using one versus another, and compares the risk-benefits across the different modalities. Issues related to all modalities including partial volume artifact, beam hardening, calibration, and motion assessment are also detailed. The review further provides data and images to illustrate differences between methods to better guide the reader in selecting an imaging method strategically. Overall, investigators should be cautious of the impact of imaging parameters on image signal or contrast-to-noise-ratios, and the need to report these settings in future publications. The effect of motion should be assessed on images and a decision made to exclude prior to segmentation. A more standardized approach to imaging bone and muscle on pQCT and MRI could enhance comparability across studies and could improve the quality of meta-analyses.

[Neurological and psychiatric aspects of some endocrine diseases. The role of neurosteroids and neuroactive steroids].

PubMed

Aszalós, Zsuzsa

2007-10-14

Regardless of their origin, neuroactive steroids are capable of modifying neural activities by modulating different types of membrane receptors. Neurosteroids are synthesized de novo in neurones and glia. Steroidogenic enzymes are found in the central nervous system. Classical steroid receptors are localized in the cytoplasm, they exert regulatory actions on the genome, and their activation causes medium- and long-term effects. Non-classical receptors are located within the membrane and act as mediators of short-term effects. Other important players are co-repressors and co-activators that can interfere with or enhance the activity of steroid receptors. Beyond their function in stress, corticosteroids play a very important role in fear, anxiety, and memory functions. Patients with Cushing's syndrome frequently develop mood disorder, reversible brain atrophy with transient memory loss, rarely delirium or psychosis. Well-known peripheral symptom is steroidal myopathy. In patients with Addison's disease the main signs are weakness of muscles, lack of energy, decreased mental functions and reduced quality of life. Estrogen and progesterone have their own respective hormone receptors, whereas allopregnanolone acts via the GABA receptors. These hormones have significant role in the development of brain, the architecture of neural circuits and dendrites, density of axonal connections, and the number of neurons. They influence maturation, neuroprotection, seizures, cognitive functions, mood, anxiety, pain, and restitution of peripheral nerves. Androgens also affect cognitive functions, pain, anxiety, mood, and additionally aggression.

Reflex-based grasping, skilled forelimb reaching, and electrodiagnostic evaluation for comprehensive analysis of functional recovery-The 7-mm rat median nerve gap repair model revisited.

PubMed

Stößel, Maria; Rehra, Lena; Haastert-Talini, Kirsten

2017-10-01

The rat median nerve injury and repair model gets increasingly important for research on novel bioartificial nerve grafts. It allows follow-up evaluation of the recovery of the forepaw functional ability with several sensitive techniques. The reflex-based grasping test, the skilled forelimb reaching staircase test, as well as electrodiagnostic recordings have been described useful in this context. Currently, no standard values exist, however, for comparison or comprehensive correlation of results obtained in each of the three methods after nerve gap repair in adult rats. Here, we bilaterally reconstructed 7-mm median nerve gaps with autologous nerve grafts (ANG) or autologous muscle-in-vein grafts (MVG), respectively. During 8 and 12 weeks of observation, functional recovery of each paw was separately monitored using the grasping test (weekly), the staircase test, and noninvasive electrophysiological recordings from the thenar muscles (both every 4 weeks). Evaluation was completed by histomorphometrical analyses at 8 and 12 weeks postsurgery. The comprehensive evaluation detected a significant difference in the recovery of forepaw functional motor ability between the ANG and MVG groups. The correlation between the different functional tests evaluated precisely displayed the recovery of distinct levels of forepaw functional ability over time. Thus, this multimodal evaluation model represents a valuable preclinical model for peripheral nerve reconstruction approaches.

Distinct Mechanisms Produce Functionally Complementary Actions of Neuropeptides that are Structurally Related but Derived from Different Precursors

PubMed Central

Vilim, F.S.; Sasaki, K.; Rybak, J.; Alexeeva, V.; Cropper, E.; Jing, J.; Orekhova, I.V.; Brezina, V.; Price, D.; Romanova, E.V.; Rubakhin, S.S.; Hatcher, N.; Sweedler, J.V.; Weiss, K.R.

2010-01-01

Many bioactive neuropeptides containing RFamide at their C-terminus have been described in both invertebrates and vertebrates. To obtain insight into the functional logic of RFamide signaling, we investigate it here in the feeding system of Aplysia. We focus on the expression, localization, and actions of two families of RFamide peptides, the FRFamides and FMRFamide, in the central neuronal circuitry and the peripheral musculature that generate the feeding movements. We describe the cloning of the FRFamide precursor protein and show that the FRFamides and FMRFamide are derived from different precursors. We map the expression of the FRFamide and FMRFamide precursors in the feeding circuitry using in-situ hybridization and immunostaining, and confirm proteolytic processing of the FRFamide precursor by mass spectrometry. We show that the two precursors are expressed in different populations of sensory neurons in the feeding system. In a representative feeding muscle, we demonstrate the presence of both FRFamides and FMRFamide and their release, probably from the processes of the sensory neurons in the muscle. Both centrally and in the periphery, the FRFamides and FMRFamide act in distinct ways, apparently through distinct mechanisms, that nevertheless, from an overall functional perspective, their actions are complementary. Together, the FRFamides and FMRFamide convert feeding motor programs from ingestive to egestive, and depress feeding muscle contractions. We conclude that these structurally related peptides, even though derived from different precursors, expressed in different neurons, and acting through different mechanisms, remain related to each other in the functional roles that they play in the system. PMID:20053896

Pathophysiology of muscle fiber necrosis induced by bupivacaine hydrochloride (Marcaine).

PubMed

Nonaka, I; Takagi, A; Ishiura, S; Nakase, H; Sugita, H

1983-01-01

A single direct injection of a local anesthetic, 0.5% bupivacaine hydrochloride (BPVC) (Marcaine), into rat soleus and extensor digitorum longus (EDL) muscles produced massive fiber necrosis with extensive phagocytosis followed by rapid regeneration, predominantly in the soleus. Since the sarcoplasmic reticulum (SR) was functionally disturbed by BPVC administration as confirmed by an in vitro study, the sarcolemmal lysis seen in the early phase of degeneration was not assumed to simply result from direct damage to the plasma membrane caused by BPVC. The extracellular fluid containing a high concentration of calcium (Ca) ions then permeated into the sarcoplasm through the defective membrane resulting in hyper-contracted myofibrils. Selective damage to the Z-line, an early sign of muscle degeneration, was shown by electron microscopy and SDS gel electrophoresis (preferential loss of alpha-actinin). Administration of leupeptin, a thiol protease inhibitor, proved to be ineffective in inhibiting the necrotic process, because the BPVC induced muscle fiber breakdown was probably too acute and fulminant to demonstrate the inhibitory effect upon the degenerative process. Well preserved satellite cells, peripheral nerves, and acetylcholinesterase activity, and the absence of fibrous tissue proliferation in this system may be responsible for the extremely rapid regeneration with complete muscle fiber type differentiation. Since the sequence of fiber breakdown induced by BPVC administration was similar to that of progressive muscular dystrophy, this chemical will be one of the most useful tools for studying the pathophysiology of fiber necrosis and regeneration in diseased muscle.

Power of performance of the thumb adductor muscles: effect of laterality and gender.

PubMed

Gutnik, Boris; Nash, Derek; Ricacho, Norberto; Hudson, Grant; Skirius, Jonas

2006-01-01

The aim of this work was to originally measure mechanical power output of the thumb adductor muscles during fast adduction of the thumb in the horizontal plane. This information will contribute to biomechanical guidelines to help clinicians, sport medicine and rehabilitation specialists in the objective functional evaluation of abnormalities of thumb adductors. Participants performed 20 fast adductions in response to audio signals. Maximum and average angular velocity and angular acceleration were measured. Tangential components of these parameters were then derived. The force of adduction was obtained from the tangential acceleration and the mass of the rotational system. The power was then calculated as the product of the force of adduction and average tangential velocity during the acceleration phase of adduction. All young and untrained males and females were strictly right handed. There was no significant difference in power between dominant and nondominant muscles for either males or females, but males developed significantly more power than females. Because adduction was performed at maximal speed, these data may be explained by the influence of parallel and series elastic elements in the muscle, as well as by influence of fast twitch fibers. Power may be used as a clinical index of the effectiveness of muscle contraction. The similarity of power outputs from dominant and nondominant thumb adductor muscles of right-handers can suggest a classical Bernstein approach. This theoretical approach purports that peripheral factors can distort central commands projected to dominant and nondominant extremities.

Impact of Aging on Proprioceptive Sensory Neurons and Intrafusal Muscle Fibers in Mice.

PubMed

Vaughan, Sydney K; Stanley, Olivia L; Valdez, Gregorio

2017-06-01

The impact of aging on proprioceptive sensory neurons and intrafusal muscle fibers (IMFs) remains largely unexplored despite the central function these cells play in modulating voluntary movements. Here, we show that proprioceptive sensory neurons undergo deleterious morphological changes in middle age (11- to 13-month-old) and old (15- to 21-month-old) mice. In the extensor digitorum longus and soleus muscles of middle age and old mice, there is a significant increase in the number of Ia afferents with large swellings that fail to properly wrap around IMFs compared with young adult (2- to 4-month-old) mice. Fewer II afferents were also found in the same muscles of middle age and old mice. Although these age-related changes in peripheral nerve endings were accompanied by degeneration of proprioceptive sensory neuron cell bodies in dorsal root ganglia (DRG), the morphology and number of IMFs remained unchanged. Our analysis also revealed normal levels of neurotrophin 3 (NT3) but dysregulated expression of the tyrosine kinase receptor C (TrkC) in aged muscles and DRGs, respectively. These results show that proprioceptive sensory neurons degenerate prior to atrophy of IMFs during aging, and in the presence of the NT3/TrkC signaling axis. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Limb myokymia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albers, J.W.; Allen, A.A.; Bastron, J.A.

Thirty-eight patients with myokymic discharges localized to limb muscles on needle electromyography had various neurologic lesions, both acute and chronic. Of the 38 patients, 27 had had previous radiation therapy and the clinical diagnosis of radiation-induced plexopathy, myelopathy, or both. For the remaining 11 patients, the diagnoses included multiple sclerosis, inflammatory polyradiculoneuropathy, ischemic neuropathy, inflammatory myopathy, and chronic disorders of the spinal cord and peripheral nerves. The clinical presentations and results of local ischemia, peripheral nerve block, and percutaneous stimulation suggest that most limb myokymic discharges arise focally at the site of a chronic peripheral nerve lesion.

Myokymia and neuromyotonia in veterinary medicine: a comparison with peripheral nerve hyperexcitability syndrome in humans.

PubMed

Vanhaesebrouck, An E; Bhatti, Sofie F M; Franklin, Robin J M; Van Ham, Luc

2013-08-01

Involuntary muscle hyperactivity can result from muscle or peripheral nerve hyperexcitability or central nervous system dysfunction. In humans, diseases causing hyperexcitability of peripheral nerves are grouped together under the term 'peripheral nerve hyperexcitability' (PNH). Hyperexcitability of the peripheral motor nerve can result into five different phenotypic main variants, i.e. fasciculations, myokymia, neuromyotonia, cramps and tetany, each with their own clinical and electromyographic characteristics. This review focuses on the most commonly described expressions of PNH in veterinary medicine, i.e. myokymia and neuromyotonia, in particular in young Jack Russell terriers. Data from 58 veterinary cases with generalized myokymia and neuromyotonia were analyzed, including unpublished treatment and follow-up data on eight Jack Russell terriers from a previous study and seven additional Jack Russell terriers. A dysfunction of the potassium channel or its associated proteins has been found in many human syndromes characterized by PNH, in particular in generalized myokymia and neuromyotonia, and is suspected to occur in veterinary medicine. Potential pathomechanisms of potassium channel dysfunction leading to signs of PNH are broad and include genetic mutations, antibody-mediated attack or ion channel maldistribution due to axonal degeneration or demyelination. A more accurate classification of the different PNH syndromes will facilitate a more rapid diagnosis and guide further research into natural occurring PNH in animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human Electro-Muscular Incapacitation (HEMI) Devices Characterization: A Comparative Study on Stress and the Physiological Effects on Swine

DTIC Science & Technology

2011-07-07

depending upon the device. As noted earlier, while the Stinger™S-200 and TASER ® X26 both resulted in tetany (sustained muscle contraction ), the cyclic...artificially maintained by the muscle contraction of the HEMI application. The stoppage of the HEMI “unmasked” the hypovolemia and the blood pressure...dropped. (2) The animals had normal blood volume with peripheral vascular resistance maintained by the HEMI ( muscle contraction ). When the HEMI

Power-duration relationship: Physiology, fatigue, and the limits of human performance.

PubMed

Burnley, Mark; Jones, Andrew M

2018-02-01

The duration that exercise can be maintained decreases as the power requirements increase. In this review, we describe the power-duration (PD) relationship across the full range of attainable power outputs in humans. We show that a remarkably small range of power outputs is sustainable (power outputs below the critical power, CP). We also show that the origin of neuromuscular fatigue differs considerably depending on the exercise intensity domain in which exercise is performed. In the moderate domain (below the lactate threshold, LT), fatigue develops slowly and is predominantly of central origin (residing in the central nervous system). In the heavy domain (above LT but below CP), both central and peripheral (muscle) fatigue are observed. In this domain, fatigue is frequently correlated with the depletion of muscle glycogen. Severe-intensity exercise (above the CP) is associated with progressive derangements of muscle metabolic homeostasis and consequent peripheral fatigue. To counter these effects, muscle activity increases progressively, as does pulmonary oxygen uptake ([Formula: see text]), with task failure being associated with the attainment of [Formula: see text] max. Although the loss of homeostasis and thus fatigue develop more rapidly the higher the power output is above CP, the metabolic disturbance and the degree of peripheral fatigue reach similar values at task failure. We provide evidence that the failure to continue severe-intensity exercise is a physiological phenomenon involving multiple interacting mechanisms which indicate a mismatch between neuromuscular power demand and instantaneous power supply. Valid integrative models of fatigue must account for the PD relationship and its physiological basis.

Estimation of whole body fat from appendicular soft tissue from peripheral quantitative computed tomography in adolescent girls

PubMed Central

Lee, Vinson R.; Blew, Rob M.; Farr, Josh N.; Tomas, Rita; Lohman, Timothy G.; Going, Scott B.

2013-01-01

Objective Assess the utility of peripheral quantitative computed tomography (pQCT) for estimating whole body fat in adolescent girls. Research Methods and Procedures Our sample included 458 girls (aged 10.7 ± 1.1y, mean BMI = 18.5 ± 3.3 kg/m2) who had DXA scans for whole body percent fat (DXA %Fat). Soft tissue analysis of pQCT scans provided thigh and calf subcutaneous percent fat and thigh and calf muscle density (muscle fat content surrogates). Anthropometric variables included weight, height and BMI. Indices of maturity included age and maturity offset. The total sample was split into validation (VS; n = 304) and cross-validation (CS; n = 154) samples. Linear regression was used to develop prediction equations for estimating DXA %Fat from anthropometric variables and pQCT-derived soft tissue components in VS and the best prediction equation was applied to CS. Results Thigh and calf SFA %Fat were positively correlated with DXA %Fat (r = 0.84 to 0.85; p <0.001) and thigh and calf muscle densities were inversely related to DXA %Fat (r = −0.30 to −0.44; p < 0.001). The best equation for estimating %Fat included thigh and calf SFA %Fat and thigh and calf muscle density (adj. R2 = 0.90; SEE = 2.7%). Bland-Altman analysis in CS showed accurate estimates of percent fat (adj. R2 = 0.89; SEE = 2.7%) with no bias. Discussion Peripheral QCT derived indices of adiposity can be used to accurately estimate whole body percent fat in adolescent girls. PMID:25147482

PubMed Central

LABBÈ, D.; BUSSU, F.; IODICE, A.

2012-01-01

SUMMARY Long-standing peripheral monolateral facial paralysis in the adult has challenged otolaryngologists, neurologists and plastic surgeons for centuries. Notwithstanding, the ultimate goal of normality of the paralyzed hemi-face with symmetry at rest, and the achievement of a spontaneous symmetrical smile with corneal protection, has not been fully reached. At the beginning of the 20th century, the main options were neural reconstructions including accessory to facial nerve transfer and hypoglossal to facial nerve crossover. In the first half of the 20th century, various techniques for static correction with autologous temporalis muscle and fascia grafts were proposed as the techniques of Gillies (1934) and McLaughlin (1949). Cross-facial nerve grafts have been performed since the beginning of the 1970s often with the attempt to transplant free-muscle to restore active movements. However, these transplants were non-vascularized, and further evaluations revealed central fibrosis and minimal return of function. A major step was taken in the second half of the 1970s, with the introduction of microneurovascular muscle transfer in facial reanimation, which, often combined in two steps with a cross-facial nerve graft, has become the most popular option for the comprehensive treatment of long-standing facial paralysis. In the second half of the 1990s in France, a regional muscle transfer technique with the definite advantages of being one-step, technically easier and relatively fast, namely lengthening temporalis myoplasty, acquired popularity and consensus among surgeons treating facial paralysis. A total of 111 patients with facial paralysis were treated in Caen between 1997 and 2005 by a single surgeon who developed 2 variants of the technique (V1, V2), each with its advantages and disadvantages, but both based on the same anatomo-functional background and aim, which is transfer of the temporalis muscle tendon on the coronoid process to the lips. For a comprehensive treatment of the paralysis, the eyelids are usually managed by Paul Tessier's technique to lengthen the levator muscle of the upper eyelid by aponeurosis interposition, combined with external blepharorrhaphy with Krastinova-Lolov's technique. Facial reanimation using lengthening temporalis myoplasty is a dynamic procedure that has its roots in the techniques of Gillies and McLaughlin. This method is a true lengthening myoplasty procedure using no intermediate grafts. In general, the results with a 1-stage combination of lengthening temporalis myoplasty and static correction of the lagophthalmos appear comparable with the major series in the literature using free microneurovascular transfers combined with cross-facial nerve grafts for longstanding peripheral monolateral facial paralysis. The obvious advantages of temporalis elongation myoplasty consist in its technical ease, a single step, low incidence of complications and markedly reduced operating time. PMID:22767978

A comprehensive approach to long-standing facial paralysis based on lengthening temporalis myoplasty.

PubMed

Labbè, D; Bussu, F; Iodice, A

2012-06-01

Long-standing peripheral monolateral facial paralysis in the adult has challenged otolaryngologists, neurologists and plastic surgeons for centuries. Notwithstanding, the ultimate goal of normality of the paralyzed hemi-face with symmetry at rest, and the achievement of a spontaneous symmetrical smile with corneal protection, has not been fully reached. At the beginning of the 20(th) century, the main options were neural reconstructions including accessory to facial nerve transfer and hypoglossal to facial nerve crossover. In the first half of the 20(th) century, various techniques for static correction with autologous temporalis muscle and fascia grafts were proposed as the techniques of Gillies (1934) and McLaughlin (1949). Cross-facial nerve grafts have been performed since the beginning of the 1970s often with the attempt to transplant free-muscle to restore active movements. However, these transplants were non-vascularized, and further evaluations revealed central fibrosis and minimal return of function. A major step was taken in the second half of the 1970s, with the introduction of microneurovascular muscle transfer in facial reanimation, which, often combined in two steps with a cross-facial nerve graft, has become the most popular option for the comprehensive treatment of long-standing facial paralysis. In the second half of the 1990s in France, a regional muscle transfer technique with the definite advantages of being one-step, technically easier and relatively fast, namely lengthening temporalis myoplasty, acquired popularity and consensus among surgeons treating facial paralysis. A total of 111 patients with facial paralysis were treated in Caen between 1997 and 2005 by a single surgeon who developed 2 variants of the technique (V1, V2), each with its advantages and disadvantages, but both based on the same anatomo-functional background and aim, which is transfer of the temporalis muscle tendon on the coronoid process to the lips. For a comprehensive treatment of the paralysis, the eyelids are usually managed by Paul Tessier's technique to lengthen the levator muscle of the upper eyelid by aponeurosis interposition, combined with external blepharorrhaphy with Krastinova-Lolov's technique. Facial reanimation using lengthening temporalis myoplasty is a dynamic procedure that has its roots in the techniques of Gillies and McLaughlin. This method is a true lengthening myoplasty procedure using no intermediate grafts. In general, the results with a 1-stage combination of lengthening temporalis myoplasty and static correction of the lagophthalmos appear comparable with the major series in the literature using free microneurovascular transfers combined with cross-facial nerve grafts for longstanding peripheral monolateral facial paralysis. The obvious advantages of temporalis elongation myoplasty consist in its technical ease, a single step, low incidence of complications and markedly reduced operating time.

Parallel evolution of tetrodotoxin resistance in three voltage-gated sodium channel genes in the garter snake Thamnophis sirtalis.

PubMed

McGlothlin, Joel W; Chuckalovcak, John P; Janes, Daniel E; Edwards, Scott V; Feldman, Chris R; Brodie, Edmund D; Pfrender, Michael E; Brodie, Edmund D

2014-11-01

Members of a gene family expressed in a single species often experience common selection pressures. Consequently, the molecular basis of complex adaptations may be expected to involve parallel evolutionary changes in multiple paralogs. Here, we use bacterial artificial chromosome library scans to investigate the evolution of the voltage-gated sodium channel (Nav) family in the garter snake Thamnophis sirtalis, a predator of highly toxic Taricha newts. Newts possess tetrodotoxin (TTX), which blocks Nav's, arresting action potentials in nerves and muscle. Some Thamnophis populations have evolved resistance to extremely high levels of TTX. Previous work has identified amino acid sites in the skeletal muscle sodium channel Nav1.4 that confer resistance to TTX and vary across populations. We identify parallel evolution of TTX resistance in two additional Nav paralogs, Nav1.6 and 1.7, which are known to be expressed in the peripheral nervous system and should thus be exposed to ingested TTX. Each paralog contains at least one TTX-resistant substitution identical to a substitution previously identified in Nav1.4. These sites are fixed across populations, suggesting that the resistant peripheral nerves antedate resistant muscle. In contrast, three sodium channels expressed solely in the central nervous system (Nav1.1-1.3) showed no evidence of TTX resistance, consistent with protection from toxins by the blood-brain barrier. We also report the exon-intron structure of six Nav paralogs, the first such analysis for snake genes. Our results demonstrate that the molecular basis of adaptation may be both repeatable across members of a gene family and predictable based on functional considerations. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Effectiveness of aquatic versus land physiotherapy in the treatment of peripheral neuropathies: a randomized controlled trial.

PubMed

Zivi, Ilaria; Maffia, Sara; Ferrari, Vanessa; Zarucchi, Alessio; Molatore, Katia; Maestri, Roberto; Frazzitta, Giuseppe

2018-05-01

To compare the effects on gait and balance of aquatic physiotherapy versus on-land training, in the context of an inpatient rehabilitation treatment tailored for peripheral neuropathies. Parallel-group, single-center, single-blind randomized controlled trial. Consecutive patients affected by peripheral neuropathy admitted in our Neuro-Rehabilitation Unit. Patients received a four-week rehabilitation program composed by daily sessions of conventional physiotherapy and three sessions/week of specific treatment (aquatic vs. on-land). Primary outcome measures were Berg Balance Scale and Dynamic Gait Index. Secondary outcome measures were Neuropathic Pain Scale, Overall Neuropathy Limitations Scale, Functional Independence Measure, Functional Ambulation Classification, Conley Scale and Medical Research Council Scale score for the strength of hip and ankle flexor and extensor muscles. For each scale, we calculated the difference between the scores at discharge and admission and compared it between the two groups. Forty patients were enrolled: 21 in the water-based rehabilitation group and 19 in the land-based one. Patients were similar between groups. When comparing the groups, we found that "in-water" patients had a significant better improvement in the Dynamic Gait Index score (6.00 (4.00, 7.25) vs. 4.00 (1.25, 6.00), P = 0.0433). On the opposite, the "on-land" group showed a better improvement of the Functional Ambulation Classification score (1.0 (0.75, 1.0) vs. 1.0 (1.0, 2.0), P = 0.0386). Aquatic physiotherapy showed an effect comparable to the land-based rehabilitation on gait and balance dysfunctions of neuropathic patients.

F wave index: A diagnostic tool for peripheral neuropathy.

PubMed

Sathya, G R; Krishnamurthy, N; Veliath, Susheela; Arulneyam, Jayanthi; Venkatachalam, J

2017-03-01

Each skeletal muscle is usually supplied by two or more nerve roots and if one nerve root is affected and the other is spared, the clinically used F wave minimum latency can still be normal. An F wave index was constructed taking into consideration the other parameters of the F wave such as persistence, chronodispersion, latency, arm-length to determine its usefulness in the diagnosis of peripheral neuropathy. This study was undertaken to construct the F wave index in the upper limb for the median nerve in normal healthy adult males and in patients with peripheral neuropathy and to compare the values obtained in both groups. This hospital-based study was carried out on 40 males who were diagnosed to have peripheral neuropathy and on 40 age matched healthy males who served as the control group. The F wave recording was done using a digitalized nerve conduction/electromyography/EP machine in a quiet and dimly lit room. All recordings were done between 0900 and 1100 h at an ambient temperature of 22°C. The F wave recording was obtained from a fully relaxed muscle by stimulating the median nerve. The median value for F wave index obtained from median nerve (abductor pollicis brevis) in patients with peripheral neuropathy [right arm - 35.85, interquartile range (IQR) - 35.26; left arm - 39.49, IQR - 39.49] was significantly lower (P=0.001) as compared to the control group (right arm - 102.62, IQR - 83.76; left arm - 77.43, IQR - 58.02). Our results showed that F wave index in upper limb was significantly lower in patients with peripheral neuropathy than the healthy controls, and could be used for early detection of peripheral neuropathy.

Brilliant Blue FCF as an Alternative Dye for Saphenous Vein Graft Marking Effect on Conduit Function

PubMed Central

Voskresensky, Igor V.; Wise, Eric S.; Hocking, Kyle M.; Li, Fan Dong; Osgood, Michael J.; Komalavilas, Padmini; Brophy, Colleen; Cheung-Flynn, Joyce

2014-01-01

IMPORTANCE Surgical skin markers are used off-label to mark human saphenous veins (HSVs) to maintain orientation before implantation as aortocoronary or peripheral arterial bypass grafts. These surgical skin markers impair functional responses of the HSV tissue. OBJECTIVES To investigate the effect of brilliant blue dye 1 (brilliant blue FCF [for food coloring]; hereinafter, FCF) as a nontoxic alternative marking dye and to determine whether FCF has pharmacological properties. DESIGN, SETTING, AND PARTICIPANTS Segments of HSVs were collected in university hospitals from patients undergoing coronary artery bypass grafting procedures immediately after harvest (unmanipulated) or after typical intraoperative surgical graft preparation (after manipulation). Rat inferior venae cavae were used to determine the pharmacological properties and cellular targets of FCF. Endothelial and smooth muscle functional responses were determined in a muscle bath, and intimal thickening in HSVs was determined after 14 days in organ culture. MAIN OUTCOMES AND MEASURES Contractile responses were measured in force and converted to stress. Smooth muscle function was expressed as maximal responses to potassium chloride depolarization contractions. Endothelial function was defined as the percentage of relaxation of maximal agonist-induced contraction. Neointimal thickness was measured by histomorphometric analysis. RESULTS Human saphenous veins stored in the presence of FCF had no loss of endothelial or smooth muscle function. Unmanipulated HSVs preserved in the presence of FCF demonstrated a significant increase in endothelial-dependent relaxation (mean [SEM], 25.2% [6.4%] vs 30.2% [6.7%]; P = .02). Application of FCF to functionally nonviable tissue significantly enhanced the smooth muscle responses (mean [SEM], 0.018 [0.004] × 105N/m2 vs 0.057 [0.016] × 105 N/m2; P = .05). Treatment with FCF reduced intimal thickness in organ culture (mean [SEM], −17.5% [2.1%] for unmanipulated HSVs vs −27.9% [3.7%] for HSVs after manipulation; P < .001). In rat inferior venae cavae, FCF inhibited the contraction induced by the P2X7 receptor agonist 2′(3′)-O-(4-benzoyl)benzoyl-adenosine-5′-triphosphate (mean [SEM], 14.8% [2.2%] vs 6.5% [1.8%]; P = .02) to an extent similar to the P2X7 receptor antagonist oxidized adenosine triphosphate (mean [SEM], 5.0% [0.9%]; P < .02 vs control) or the pannexin hemichannel inhibitor probenecid (mean [SEM], 7.3% [1.6%] and 4.7% [0.9%] for 0.5mM and 2mM, respectively; P < .05). CONCLUSIONS AND RELEVANCE Treatment with FCF did not impair endothelial or smooth muscle function in HSVs. Brilliant blue FCF enhanced endothelial-dependent relaxation, restored smooth muscle function, and prevented intimal hyperplasia in HSVs in organ culture. These pharmacological properties of FCF may be due to P2X7 receptor or pannexin channel inhibition. Brilliant blue FCF is an alternative, nontoxic marking dye that may improve HSV conduit function and decrease intimal hyperplasia. PMID:25251505

Brilliant blue FCF as an alternative dye for saphenous vein graft marking: effect on conduit function.

PubMed

Voskresensky, Igor V; Wise, Eric S; Hocking, Kyle M; Li, Fan Dong; Osgood, Michael J; Komalavilas, Padmini; Brophy, Colleen; Cheung-Flynn, Joyce

2014-11-01

Surgical skin markers are used off-label to mark human saphenous veins (HSVs) to maintain orientation before implantation as aortocoronary or peripheral arterial bypass grafts. These surgical skin markers impair functional responses of the HSV tissue. To investigate the effect of brilliant blue dye 1 (brilliant blue FCF [for food coloring]; hereinafter, FCF) as a nontoxic alternative marking dye and to determine whether FCF has pharmacological properties. Segments of HSVs were collected in university hospitals from patients undergoing coronary artery bypass grafting procedures immediately after harvest (unmanipulated) or after typical intraoperative surgical graft preparation (after manipulation). Rat inferior venae cavae were used to determine the pharmacological properties and cellular targets of FCF. Endothelial and smooth muscle functional responses were determined in a muscle bath, and intimal thickening in HSVs was determined after 14 days in organ culture. Contractile responses were measured in force and converted to stress. Smooth muscle function was expressed as maximal responses to potassium chloride depolarization contractions. Endothelial function was defined as the percentage of relaxation of maximal agonist-induced contraction. Neointimal thickness was measured by histomorphometric analysis. Human saphenous veins stored in the presence of FCF had no loss of endothelial or smooth muscle function. Unmanipulated HSVs preserved in the presence of FCF demonstrated a significant increase in endothelial-dependent relaxation (mean [SEM], 25.2% [6.4%] vs 30.2% [6.7%]; P = .02). Application of FCF to functionally nonviable tissue significantly enhanced the smooth muscle responses (mean [SEM], 0.018 [0.004] × 10⁵ N/m² vs 0.057 [0.016] × 10⁵ N/m²; P = .05). Treatment with FCF reduced intimal thickness in organ culture (mean [SEM], -17.5% [2.1%] for unmanipulated HSVs vs -27.9% [3.7%] for HSVs after manipulation; P < .001). In rat inferior venae cavae, FCF inhibited the contraction induced by the P2X7 receptor agonist 2'(3')-O-(4-benzoyl)benzoyl-adenosine-5'-triphosphate (mean [SEM], 14.8% [2.2%] vs 6.5% [1.8%]; P = .02) to an extent similar to the P2X7 receptor antagonist oxidized adenosine triphosphate (mean [SEM], 5.0% [0.9%]; P < .02 vs control) or the pannexin hemichannel inhibitor probenecid (mean [SEM], 7.3% [1.6%] and 4.7% [0.9%] for 0.5mM and 2mM, respectively; P < .05). Treatment with FCF did not impair endothelial or smooth muscle function in HSVs. Brilliant blue FCF enhanced endothelial-dependent relaxation, restored smooth muscle function, and prevented intimal hyperplasia in HSVs in organ culture. These pharmacological properties of FCF may be due to P2X7 receptor or pannexin channel inhibition. Brilliant blue FCF is an alternative, nontoxic marking dye that may improve HSV conduit function and decrease intimal hyperplasia.

Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

PubMed Central

Nyberg, Michael; Piil, Peter; Egelund, Jon; Sprague, Randy S; Mortensen, Stefan P; Hellsten, Ylva

2015-01-01

Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal knee-extensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. Sildenafil increased leg O2 delivery (6–9%) and leg O2 uptake (10–12%) at all three exercise intensities in older but not young subjects. The increase in leg O2 delivery with sildenafil in the older subjects correlated with the increase in leg O2 uptake (r2 = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age. PMID:26272735

Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease.

PubMed

Cuthbertson, Daniel J; Shojaee-Moradie, Fariba; Sprung, Victoria S; Jones, Helen; Pugh, Christopher J A; Richardson, Paul; Kemp, Graham J; Barrett, Mark; Jackson, Nicola C; Thomas, E Louise; Bell, Jimmy D; Umpleby, A Margot

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR. © 2016 Authors; published by Portland Press Limited.

Stabilization, Rolling, and Addition of Other Extracellular Matrix Proteins to Collagen Hydrogels Improve Regeneration in Chitosan Guides for Long Peripheral Nerve Gaps in Rats.

PubMed

Gonzalez-Perez, Francisco; Cobianchi, Stefano; Heimann, Claudia; Phillips, James B; Udina, Esther; Navarro, Xavier

2017-03-01

Autograft is still the gold standard technique for the repair of long peripheral nerve injuries. The addition of biologically active scaffolds into the lumen of conduits to mimic the endoneurium of peripheral nerves may increase the final outcome of artificial nerve devices. Furthermore, the control of the orientation of the collagen fibers may provide some longitudinal guidance architecture providing a higher level of mesoscale tissue structure. To evaluate the regenerative capabilities of chitosan conduits enriched with extracellular matrix-based scaffolds to bridge a critical gap of 15 mm in the rat sciatic nerve. The right sciatic nerve of female Wistar Hannover rats was repaired with chitosan tubes functionalized with extracellular matrix-based scaffolds fully hydrated or stabilized and rolled to bridge a 15 mm nerve gap. Recovery was evaluated by means of electrophysiology and algesimetry tests and histological analysis 4 months after injury. Stabilized constructs enhanced the success of regeneration compared with fully hydrated scaffolds. Moreover, fibronectin-enriched scaffolds increased muscle reinnervation and number of myelinated fibers compared with laminin-enriched constructs. A mixed combination of collagen and fibronectin may be a promising internal filler for neural conduits for the repair of peripheral nerve injuries, and their stabilization may increase the quality of regeneration over long gaps. Copyright © 2017 by the Congress of Neurological Surgeons

Effectiveness of Spiritist "passe" (Spiritual healing) for anxiety levels, depression, pain, muscle tension, well-being, and physiological parameters in cardiovascular inpatients: A randomized controlled trial.

PubMed

Carneiro, Élida Mara; Barbosa, Luana Pereira; Marson, Jorge Marcelo; Terra, Juverson Alves; Martins, Claudio Jacinto Pereira; Modesto, Danielle; Resende, Luiz Antônio Pertili Rodrigues de; Borges, Maria de Fátima

2017-02-01

Biofield therapies, such as laying on of hands, are used in association with Conventional Medicine as Spiritist "passe", among others. The aim of this study was to evaluate anxiety, depression, pain, muscle tension and well-being, as well as physiological parameters in cardiovascular inpatients submitted to the Spiritist "passe", sham, and no intervention. In the total, 41 cardiovascular inpatients submitted to the Spiritist "passe", sham, and no intervention during a 10-min period on 3 consecutive days. They were evaluated through anxiety and depression level, pain, the perceptions of muscle tension and well-being and physiological parameters, before and after interventions. A significant reduction (p=0.001) in anxiety scores and muscle tension (p=0.011), improvement of well-being (p=0.003) and a significant increase in peripheral oxyhemoglobin saturation scores (p=0.028) were observed in Spiritist "passe" patients, and a significant reduction (p=0.028) of muscle tension and improvement of well-being (p=0.045) in sham patients. However, muscle tension reduction (p=0.003) and improvement of well-being (p=0.003) were more accentuated in the Spiritist "passe" compared to sham and no intervention. Results suggest that the Spiritist "passe" appeared to be effective, reducing anxiety level and the perception of muscle tension, consequently improving peripheral oxyhemoglobin saturation and the sensation of well-being compared to sham and no intervention in cardiovascular inpatients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neuromodulation of the neural circuits controlling the lower urinary tract

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Gerasimenko, Yury P.; Taccola, Giuliano; Edgerton, V. Reggie

2017-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. PMID:27381425

The 'sensory tolerance limit': A hypothetical construct determining exercise performance?

PubMed

Hureau, Thomas J; Romer, Lee M; Amann, Markus

2018-02-01

Neuromuscular fatigue compromises exercise performance and is determined by central and peripheral mechanisms. Interactions between the two components of fatigue can occur via neural pathways, including feedback and feedforward processes. This brief review discusses the influence of feedback and feedforward mechanisms on exercise limitation. In terms of feedback mechanisms, particular attention is given to group III/IV sensory neurons which link limb muscle with the central nervous system. Central corollary discharge, a copy of the neural drive from the brain to the working muscles, provides a signal from the motor system to sensory systems and is considered a feedforward mechanism that might influence fatigue and consequently exercise performance. We highlight findings from studies supporting the existence of a 'critical threshold of peripheral fatigue', a previously proposed hypothesis based on the idea that a negative feedback loop operates to protect the exercising limb muscle from severe threats to homeostasis during whole-body exercise. While the threshold theory remains to be disproven within a given task, it is not generalisable across different exercise modalities. The 'sensory tolerance limit', a more theoretical concept, may address this issue and explain exercise tolerance in more global terms and across exercise modalities. The 'sensory tolerance limit' can be viewed as a negative feedback loop which accounts for the sum of all feedback (locomotor muscles, respiratory muscles, organs, and muscles not directly involved in exercise) and feedforward signals processed within the central nervous system with the purpose of regulating the intensity of exercise to ensure that voluntary activity remains tolerable.

Contractile properties of skinned muscle fibres from young and adult normal and dystrophic (mdx) mice.

PubMed Central

Williams, D A; Head, S I; Lynch, G S; Stephenson, D G

1993-01-01

1. Single muscle fibres were enzymatically isolated from the soleus and extensor digitorum longus (EDL) muscles of genetically dystrophic mdx and normal (C57BL/10) mice aged 3-6 or 17-23 weeks. 2. Fibres of both muscles were chemically skinned with the non-ionic detergent Triton X-100 (2% v/v). Ca(2+)- and Sr(2+)-activated contractile responses were recorded and comparisons were made between several contractile parameters of various fibre types of normal and dystrophic mice of similar age. 3. There were no significant differences in the following contractile parameters of skinned fibres of normal and mdx mice of the same age: sensitivity to activating Ca2+ (pCa50) or Sr2+ (pSr50) and differential sensitivity to the activating ions (pCa50-pSr50). However the maximum isometric tension (Po) and the frequency of myofibrillar force oscillations in EDL fast-twitch fibres of young mdx mice were significantly lower than those of soleus fast-twitch fibres of the same animals, or fast-twitch fibres (EDL or soleus) of normal mice. 4. Age-related differences were apparent in some contractile parameters of both normal and mdx mice. In particular the steepness of force-pCa and force-pSr curves increased with age in normal mice, yet decreased with age in fibres of mdx mice. 5. A fluorescent probe, ethidium bromide, which interchelates with DNA, was used with laser-scanning confocal microscopy to determine the distribution of myonuclei in fibres. Fibres isolated from either muscle type of normal animals displayed a characteristic peripheral spiral of myonuclei. Fibres from muscles of mdx mice displayed three major patterns of nuclear distribution; the normal peripheral spiral, long central strands of nuclei, and a mixture of these two patterns. 6. The contractile characteristics of mdx fibres were not markedly influenced by the nuclear distribution pattern in that there were no discernible differences in the major contractile parameters (the Hill coefficients nCa and nSr, which are associated with the steepness of the Ca2+ and Sr2+ activation curves, pCa50, pSr50, pCa50-pSr50) of skinned fibres possessing peripheral or central nuclei. However, except for nSr, these values were all lower in individual fibres which displayed similar proportions of central and peripheral nuclei. The presence of mixed nucleation and absence of fibres with embryonic contractile characteristics in mdx mice suggest that the dystrophin-negative fibres can repair locally occurring muscle damage. Images Fig. 1 Fig. 1(Contd.) Fig. 4 Fig. 5 PMID:8487206

The effects of hyperventilation on postural control mechanisms.

PubMed

Sakellari, V; Bronstein, A M; Corna, S; Hammon, C A; Jones, S; Wolsley, C J

1997-09-01

The effect of hyperventilation on postural balance was investigated. Voluntary hyperventilation increased body sway in normal subjects, particularly in the sagittal plane. The possibility that this hyperventilation-induced unsteadiness is due to interference with lower limb somatosensory input, vestibular reflexes or cerebellar function was assessed. (i) The effect of hyperventilation on peripheral compound sensory action potentials (SAPs) and somatosensory evoked potentials (SEPs) (recorded centrally, from the scalp) elicited by electrical stimulation of the sural nerve was measured in six normal adults. A reduction in the scalp SEP amplitude and an increase in the peripheral SAP amplitude were observed during hyperventilation, which reversed during the recovery period. These changes indicate increased peripheral neural excitability which could lead to a higher level of ectopic activity; the latter would interfere with central reception of peripheral input. (ii) The click-evoked vestibulo-collic reflex was recorded to study the effect of hyperventilation on vestibulo-spinal activity. EMG recordings from both sternocleidomastoid muscles of six healthy subjects were made in response to loud clicks presented to either ear. Neither the amplitude nor the latency of the response were altered significantly by hyperventilation. (iii) Eye-movement recordings were obtained in the six normal subjects to assess the effect of hyperventilation on the vestibulo-ocular reflex and its visual suppression, the latter being a function largely mediated by the cerebellum; no changes were detected. (iv) Three-dimensional eye-movement recordings and body-sway measurements were obtained in six patients with longstanding unilateral vestibular loss in order to evaluate if hyperventilation disrupts vestibular compensation. In all patients, a horizontal nystagmus either appeared or was significantly enhanced for > or = 60 s after voluntary hyperventilation. Sway was also enhanced by hyperventilation in these patients, particularly in the frontal plane. This study suggests that hyperventilation disrupts mechanisms mediating vestibular compensation. The increase in sway may be, at least partly, mediated by deranged peripheral and central somatosensory signals from the lower limbs. Hyperventilation seems to spare vestibular reflex activity and cerebellar-mediated eye movements.

Altered EMG patterns in diabetic neuropathic and not neuropathic patients during step ascending and descending.

PubMed

Spolaor, Fabiola; Sawacha, Zimi; Guarneri, Gabriella; Del Din, Silvia; Avogaro, Angelo; Cobelli, Claudio

2016-12-01

Diabetic peripheral neuropathy (DPN) causes motor control alterations during daily life activities. Tripping during walking or stair climbing is the predominant cause of falls in the elderly subjects with DPN and without (NoDPN). Surface Electromyography (sEMG) has been shown to be a valid tool for detecting alterations of motor functions in subjects with DPN. This study aims at investigating the presence of functional alterations in diabetic subjects during stair climbing and at exploring the relationship between altered muscle activation and temporal parameter. Lower limb muscle activities, temporal parameters and speed were evaluated in 50 subjects (10 controls, 20 with DPN, 20 without DPN), while climbing up and down a stair, using sEMG, three-dimentional motion capture and force plates. Magnitude and timing of sEMG linear envelopes peaks were extracted. Level walking was used as reference condition for the comparison with step negotiation. sEMG, speed and temporal parameters revealed significant differences among all groups of patients. Results showed an association between earlier activation of lower limb muscles and reduced speed in subjects with DPN. Speed and temporal parameters significantly correlated with sEMG (p<0.05). The findings of this study are encouraging and could be used to improve rehabilitation programs aiming at reducing falls risk in diabetic subjects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Discharge rates in electromyography distinguish early between peripheral and central paresis.

PubMed

Jürgens, Tim P; Puchner, Christoph; Schulte-Mattler, Wilhelm J

2012-10-01

Abnormally increased discharge rates (DRs) of motor unit potentials on concentric needle electromyography (CNEMG) indicate a loss of motor units in peripheral neurogenic lesions. To determine when increased DRs occur during the course of a peripheral nerve lesion, we retrospectively analyzed CNEMG recordings of 19 patients with acute weakness of peripheral origin. The initial CNEMG studies took place from 3.7 hours to 10 days after the onset of the lesion. Abnormally increased DRs (≥20/s) were found in all but 1 of the muscles in which MRC grade was <4. Peripheral neurogenic damage was confirmed in all patients thereafter. The DRs depended on neither the kind of lesion nor the time between onset and CNEMG examination. The measurement of DRs of motor unit potentials is helpful immediately after a sudden paresis of MRC grade 3 or worse to differentiate between a central and a peripheral lesion. Copyright © 2012 Wiley Periodicals, Inc.

Autologous transplantation with fewer fibers repairs large peripheral nerve defects

PubMed Central

Deng, Jiu-xu; Zhang, Dian-yin; Li, Ming; Weng, Jian; Kou, Yu-hui; Zhang, Pei-xun; Han, Na; Chen, Bo; Yin, Xiao-feng; Jiang, Bao-guo

2017-01-01

Peripheral nerve injury is a serious disease and its repair is challenging. A cable-style autologous graft is the gold standard for repairing long peripheral nerve defects; however, ensuring that the minimum number of transplanted nerve attains maximum therapeutic effect remains poorly understood. In this study, a rat model of common peroneal nerve defect was established by resecting a 10-mm long right common peroneal nerve. Rats receiving transplantation of the common peroneal nerve in situ were designated as the in situ graft group. Ipsilateral sural nerves (10–30 mm long) were resected to establish the one sural nerve graft group, two sural nerves cable-style nerve graft group and three sural nerves cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long. To reduce the barrier effect due to invasion by surrounding tissue and connective-tissue overgrowth between neural stumps, small gap sleeve suture was used in both proximal and distal terminals to allow repair of the injured common peroneal nerve. At three months postoperatively, recovery of nerve function and morphology was observed using osmium tetroxide staining and functional detection. The results showed that the number of regenerated nerve fibers, common peroneal nerve function index, motor nerve conduction velocity, recovery of myodynamia, and wet weight ratios of tibialis anterior muscle were not significantly different among the one sural nerve graft group, two sural nerves cable-style nerve graft group, and three sural nerves cable-style nerve graft group. These data suggest that the repair effect achieved using one sural nerve graft with a lower number of nerve fibers is the same as that achieved using the two sural nerves cable-style nerve graft and three sural nerves cable-style nerve graft. This indicates that according to the ‘multiple amplification’ phenomenon, one small nerve graft can provide a good therapeutic effect for a large peripheral nerve defect. PMID:29323049

Expression pattern and function of tyrosine receptor kinase B isoforms in rat mesenteric arterial smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Otani, Kosuke; Okada, Muneyoshi; Yamawaki, Hideyuki, E-mail: yamawaki@vmas.kitasato-u.ac.jp

Tyrosine receptor kinaseB (TrkB) is a high affinity receptor for brain-derived neurotrophic factor (BDNF). TrkB isoforms involve full length TrkB (TrkB FL) and truncated TrkB type1 (TrkB T1) and type 2 (TrkB T2) in rats. The aim of present study was to explore their expression pattern and function in mesenteric arterial smooth muscle cells (MASMCs). The expression of TrkB isoform protein and mRNA was examined by Western blotting, immunofluorescence and quantitative RT-PCR analyses. Cell proliferation was measured by a bromodeoxyuridine (BrdU) incorporation assay. Cell migration was measured by a Boyden chamber assay. Cell morphology was observed with a phase-contrast microscope.more » Protein and mRNA expression of BDNF and TrkB isoforms was confirmed in MASMCs. Expression level of TrkB FL was less, while that of TrkB T1 was the highest in MASMCs. Although BDNF increased phosphorylation of ERK, it had no influence on migration and proliferation of MASMCs. TrkB T1 gene knockdown by a RNA interference induced morphological changes and reduced expression level of α-smooth muscle actin (α-SMA) in MASMCs. Similar morphological changes and reduced α-SMA expression were induced in MASMCs by a Rho kinase inhibitor, Y-27632. In conclusion, we for the first time demonstrate that TrkB T1 expressed highly in MASMCs contributes to maintain normal cell morphology possibly via regulation of Rho activity. This study firstly defined expression level of TrkB isoforms and partly revealed their functions in peripheral vascular cells. - Highlights: • BDNF-TrkB axis mediates neurogenesis, growth, differentiation and survival. • Expression pattern and function of TrkB in vascular smooth muscle remain unclear. • Expression of TrkB FL is low, while that of TrkB T1 is the highest. • TrkB T1 contributes to maintain normal morphology possibly via activating Rho.« less

Four days of simulated shift work reduces insulin sensitivity in humans.

PubMed

Bescos, R; Boden, M J; Jackson, M L; Trewin, A J; Marin, E C; Levinger, I; Garnham, A; Hiam, D S; Falcao-Tebas, F; Conte, F; Owens, J A; Kennaway, D J; McConell, G K

2018-06-01

The aim of this study was to investigate the effects of 4 consecutive simulated night shifts on glucose homeostasis, mitochondrial function and central and peripheral rhythmicities compared with a simulated day shift schedule. Seventeen healthy adults (8M:9F) matched for sleep, physical activity and dietary/fat intake participated in this study (night shift work n = 9; day shift work n = 8). Glucose tolerance and insulin sensitivity before and after 4 nights of shift work were measured by an intravenous glucose tolerance test and a hyperinsulinaemic euglycaemic clamp respectively. Muscles biopsies were obtained to determine insulin signalling and mitochondrial function. Central and peripheral rhythmicities were assessed by measuring salivary melatonin and expression of circadian genes from hair samples respectively. Fasting plasma glucose increased (4.4 ± 0.1 vs. 4.6 ± 0.1 mmol L -1 ; P = .001) and insulin sensitivity decreased (25 ± 7%, P < .05) following the night shift, with no changes following the day shift. Night shift work had no effect on skeletal muscle protein expression (PGC1α, UCP3, TFAM and mitochondria Complex II-V) or insulin-stimulated pAkt Ser473, pTBC1D4Ser318 and pTBC1D4Thr642. Importantly, the metabolic changes after simulated night shifts occurred despite no changes in the timing of melatonin rhythmicity or hair follicle cell clock gene expression across the wake period (Per3, Per1, Nr1d1 and Nr1d2). Only 4 days of simulated night shift work in healthy adults is sufficient to reduce insulin sensitivity which would be expected to increase the risk of T2D. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

[Operative treatment of painful neuromas].

PubMed

Stokvis, Annemieke; Coert, J Henk

2011-01-01

3-5% of patients with traumatic or iatrogenic peripheral nerve injury develop a painful neuroma, especially following trauma of small cutaneous sensory nerve branches. Neuroma pain is difficult to treat and often leads to loss of function and reduction of quality of life. Patients with a painful neuroma present with spontaneous electric, shooting or burning pain, allodynia, hyperalgesia and cold intolerance. The diagnosis is based on the medical history and physical examination, supplemented by Tinel's test and a diagnostic nerve blockade. Lasting pain relief is possible by means of surgical neuroma treatment performed by a plastic surgeon. Surgical treatment consists of repair or denervation of the nerve with relocation of the nerve stump in bone or muscle tissue or a vein. Referral of neuroma patients without delay to a plastic surgeon or multidisciplinary consultation is important, because the symptoms become increasingly difficult to treat over time. 3-5% of patients with traumatic or iatrogenic peripheral nerve injury develop a painful neuroma, especially following trauma of small cutaneous sensory nerve branches. Neuroma pain is difficult to treat and often leads to loss of function and reduction of quality of life. Patients with a painful neuroma present with spontaneous electric, shooting or burning pain, allodynia, hyperalgesia and cold intolerance. The diagnosis is based on the medical history and physical examination, supplemented by Tinel's test and a diagnostic nerve blockade. Lasting pain relief is possible by means of surgical neuroma treatment performed by a plastic surgeon. Surgical treatment consists of repair or denervation of the nerve with relocation of the nerve stump in bone or muscle tissue or a vein. Referral of neuroma patients without delay to a plastic surgeon or multidisciplinary consultation is important, because the symptoms become increasingly difficult to treat over time.

Upregulation of Immunoproteasome Subunits in Myositis Indicates Active Inflammation with Involvement of Antigen Presenting Cells, CD8 T-Cells and IFNγ

PubMed Central

Ghannam, Khetam; Martinez-Gamboa, Lorena; Spengler, Lydia; Krause, Sabine; Smiljanovic, Biljana; Bonin, Marc; Bhattarai, Salyan; Grützkau, Andreas; Burmester, Gerd-R.

2014-01-01

Objective In idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers. Methods Expression of constitutive (PSMB5, -6, -7) and corresponding immunoproteasomal subunits (PSMB8, -9, -10) was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. Results Real-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFNγ expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. Conclusions Immunoproteasomes seem to indicate IIM activity and suggest that dominant involvement of antigen processing and presentation may qualify these diseases exemplarily for the evolving therapeutic concepts of immunoproteasome specific inhibition. PMID:25098831

Upregulation of immunoproteasome subunits in myositis indicates active inflammation with involvement of antigen presenting cells, CD8 T-cells and IFNΓ.

PubMed

Ghannam, Khetam; Martinez-Gamboa, Lorena; Spengler, Lydia; Krause, Sabine; Smiljanovic, Biljana; Bonin, Marc; Bhattarai, Salyan; Grützkau, Andreas; Burmester, Gerd-R; Häupl, Thomas; Feist, Eugen

2014-01-01

In idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers. Expression of constitutive (PSMB5, -6, -7) and corresponding immunoproteasomal subunits (PSMB8, -9, -10) was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. Real-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFNγ expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. Immunoproteasomes seem to indicate IIM activity and suggest that dominant involvement of antigen processing and presentation may qualify these diseases exemplarily for the evolving therapeutic concepts of immunoproteasome specific inhibition.

Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons

PubMed Central

Titus-Mitchell, Haley E.; Bullinger, Katie L.; Kraszpulski, Michal; Nardelli, Paul; Cope, Timothy C.

2011-01-01

Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75–95% synaptic losses) and on the proximal 100 μm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons. PMID:21832035

Antiobesity efficacy of GLP-1 receptor agonist liraglutide is associated with peripheral tissue-specific modulation of lipid metabolic regulators.

PubMed

Decara, Juan; Arrabal, Sergio; Beiroa, Daniel; Rivera, Patricia; Vargas, Antonio; Serrano, Antonia; Pavón, Francisco Javier; Ballesteros, Joan; Dieguez, Carlos; Nogueiras, Rubén; Rodríguez de Fonseca, Fernando; Suárez, Juan

2016-11-12

To investigate the role of glucagon-like-peptide-1 receptor (GLP-1R) in peripheral lipid metabolism. Both lean and high-fat diet (HFD)-induced obesity (DIO) rats were used to compare the peripheral effects of the subcutaneous and repeated administration of the GLP-1R agonist liraglutide on the expression of key regulators involved in lipid metabolism, β-oxidation and thermogenesis in liver, abdominal muscle, and epididymal white adipose tissue (eWAT). We observed that liraglutide reduced caloric intake, body weight, and plasma levels of triglycerides and VLDL in a diet-independent manner. However, changes in liver fat content and the expression of lipid metabolism regulators were produced in a diet and tissue-dependent manner. In lean rats, liraglutide increased the gene/protein expression of elements involved in lipogenesis (ChREBP, Acaca/ACC, Fasn/FAS, Scd1/SCD1, PPARα/γ), β-oxidation (CPT1b), and thermogenesis (Cox4i1, Ucp1/UCP1) in eWAT and muscle, which suggest an increase in fatty-acid flux and utilization to activate energy expenditure. Regarding DIO rats, the specific reduction of liver lipid content by liraglutide was associated with a decreased expression of main elements involved in lipogenesis (phospho-ACC), peroxisomal β-oxidation (ACOX1), and lipid flux/storage (Pparγ/PPARγ) in liver, which suggest a recovery of lipid homeostasis. Interestingly, the muscle of DIO rats treated with liraglutide showed a decreased expression of PPARγ and the thermogenic factor UCP1. These results help us to better understand the peripheral mechanisms regulating lipid metabolism that underlay the effectiveness of GLP-1 analogues for the treatment of diabetes and obesity. © 2016 BioFactors, 42(6):600-611, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Contribution of SRF, Elk-1, and myocardin to airway smooth muscle remodeling in heaves, an asthma-like disease of horses.

PubMed

Chevigny, Mylène; Guérin-Montpetit, Karine; Vargas, Amandine; Lefebvre-Lavoie, Josiane; Lavoie, Jean-Pierre

2015-07-01

Myocyte hyperplasia and hypertrophy contribute to the increased mass of airway smooth muscle (ASM) in asthma. Serum-response factor (SRF) is a transcription factor that regulates myocyte differentiation in vitro in vascular and intestinal smooth muscles. When SRF is associated with phosphorylated (p)Elk-1, it promotes ASM proliferation while binding to myocardin (MYOCD) leading to the expression of contractile elements in these tissues. The objective of this study was therefore to characterize the expression of SRF, pElk-1, and MYOCD in ASM cells from central and peripheral airways in heaves, a spontaneously occurring asthma-like disease of horses, and in controls. Six horses with heaves and five aged-matched controls kept in the same environment were studied. Nuclear protein expression of SRF, pElk-1, and MYOCD was evaluated in peripheral airways and endobronchial biopsies obtained during disease remission and after 1 and 30 days of naturally occurring antigenic exposure using immunohistochemistry and immunofluorescence techniques. Nuclear expression of SRF (P = 0.03, remission vs. 30 days) and MYOCD (P = 0.05, controls vs. heaves at 30 days) increased in the peripheral airways of horses with heaves during disease exacerbation, while MYOCD (P = 0.04, remission vs. 30 days) decreased in the central airways of control horses. No changes were observed in the expression of pElk-1 protein in either tissue. In conclusion, SRF and its cofactor MYOCD likely contribute to the hypertrophy of peripheral ASM observed in equine asthmatic airways, while the remodeling of the central airways is more static or involves different transcription factors. Copyright © 2015 the American Physiological Society.

The pharmacological management of post-stroke muscle spasticity.

PubMed

Bakheit, Abdel Magid O

2012-12-01

Muscle hypertonia following upper motor neurone lesions (referred to here as 'spasticity') is a common problem in patients with neurological disease, and its management is one of the major challenges in clinical practice. Understanding the pathogenesis and clinical course of spasticity is essential for the effective management of this condition. The hypertonia initially results from increased excitability of the alpha motor neurones due to an imbalance between the excitatory and inhibitory influences of the vestibulospinal and reticulospinal tracts. This is the 'neural component' of muscle hypertonia. However, usually within 3-4 weeks, changes in the structure and mechanical properties of the paralysed muscles and the effect of thixotropy also contribute to the hypertonia. The selection of the optimal treatment option is often influenced by whether the neural or the non-neural component is more pronounced. Muscle spasticity often interferes with motor function or causes distressing symptoms, such as painful muscle spasms. If untreated, spasticity may also lead to soft tissue shortening (fixed contractures). However, spasticity can also be beneficial to patients. For example, despite severe leg muscle weakness, most hemiplegic patients are able to walk because the spasticity of the extensor muscles braces the lower limb in a rigid pillar. Other reported benefits of spasticity include the maintenance of muscle bulk and bone mineral density and possibly a reduced risk of lower limb deep vein thrombosis. Several factors, such as skin pressure sores, faecal impaction, urinary tract infections and stones in the urinary bladder, can aggravate muscle spasticity. These factors should always be looked for as their adequate treatment is often sufficient to reduce muscle tone without the need for specific antispasticity medication. Therefore, a careful evaluation of the patient's symptoms and their impact on function, and the setting of clear and realistic therapy goals are important prerequisites to treatment. The best treatment outcomes are usually achieved when pharmacological and non-pharmacological treatment modalities are used in tandem. Different drugs are available for the management of spasticity, including oral muscle relaxants, anticonvulsant drugs, intrathecal baclofen, cannabis extract, phenol and alcohol (for peripheral nerve blocks) and botulinum toxin injections. Similarly, there is a range of non-pharmacological methods of treatment, e.g. regular muscle stretching, the use of splints and orthoses, electrical stimulation, etc. Although these are not discussed here, this should not detract from the importance of combining them with antispasticity drugs in order to maximize the clinical benefit of treatment.

Anorectal and Pelvic Pain.

PubMed

Bharucha, Adil E; Lee, Tae Hee

2016-10-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the 3 most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first 2 conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacological, behavioral, and physical therapy. Opioids should be avoided, and surgical treatment has a limited role, primarily in refractory interstitial cystitis. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Ultrastructural findings in lung biopsy material from children with congenital heart defects.

PubMed Central

Meyrick, B.; Reid, L.

1980-01-01

The ultrastructural features of pulmonary arteries are described in lung biopsy material from 6 children with congenital heart defects. Right ventricular hypertrophy was found in all 6 children and increased pulmonary artery pressure in all but one. The presence of muscle in smaller and more peripheral arteries than expected for the age of the child was detected in all cases. Ultrastructural examination of the peripheral arteries revealed, for the first time, in the nonmuscular regions of human arterial walls, pericytes and intermediate cells (previously shown to be precursor smooth-muscle cells); in addition, new arterial muscle was found in the normally nonmuscular region. In the 4 cases where medial thickness of the normally muscular arteries was increased, the smooth-muscle cells were hypertrophied and the extracellular connective tissue increased. In all cases, junctions between endothelial cells and smooth-muscle cells, intermediate cells, or pericytes were found. These changes are similar to those described in the rat with hypoxia-induced pulmonary hypertension. In addition, in 2 of the 6 cases, bundles of nerve axons in Schwann cell sheaths were found in adventitial layer of small, intraacinar muscular arteries (not previously demonstrated ultrastructurally at this site in the human lung); varicosities with agranular and granular vesicles, probably adrenergic, were also identified. Images Figure 4 Figure 5 Figure 1 Figure 2 Figure 3 PMID:7446706

M-wave normalization of EMG signal to investigate heat stress and fatigue.

PubMed

Girard, Olivier; Bishop, David J; Racinais, Sébastien

2018-05-01

We examined the extent to which peripheral changes affect EMG signal adjustments during repeated sprinting in temperate and hot conditions. Randomised, crossover study. Ten males performed 10×6-s 'all-out' cycling sprints (recovery=30s) in either a temperate (24°C/30%rH) or a hot (35°C/40%rH) environment with concomitant surface EMG recordings of the vastus lateralis (VL) and rectus femoris (RF). In addition, peak-to-peak M-wave amplitudes were obtained for each muscle after each sprint (i.e., 15s into recovery). For both the VL and RF muscles RMS decreased across sprint repetitions (P<0.01), while significantly lower values for the VL (P=0.012), but not the RF (P=0.096), occurred in hot vs. temperate conditions. M-wave-normalised RMS for VL muscle decreased across sprint repetitions (P=0.030), with no condition or interaction effects (both P>0.621). M-wave-normalised RMS for the RF muscle was lower in the heat (P<0.034), with no significant sprint or interaction effects (both P>0.240). Controlling for changes in maximal M-wave amplitude of the quadriceps muscles after each bout of a repeated cycling exercise in hot and temperate conditions allows researchers to account for fatigue- and/or heat-induced neural and peripheral adjustments. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

[Oculo-auricular phenomenon and its value in neurologic diagnosis].

PubMed

Wagner, A; Röder, H; Pöschel, E; Mundt, B

1984-09-01

The oculoauricular phenomenon is a synergism between an external eye muscle, the m. rectus lateralis, and the facialis innervated m. retroauricularis. In the neurological diagnostic this phenomenon permits a differentiation between the abducens nerve paresis of peripheral and of nuclear origine. In addition to this electromyographic examination from the m. retroauricularis can discover disturbances of the neuromuscular transmission and facilitate an early prognostic estimation of peripheral facialis paresis.

Deficiency of electroneutral K+-Cl- cotransporter 3 causes a disruption in impulse propagation along peripheral nerves.

PubMed

Sun, Yuan-Ting; Lin, Thy-Sheng; Tzeng, Shun-Fen; Delpire, Eric; Shen, Meng-Ru

2010-10-01

Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K(+)-Cl(-) cotransporter (KCC) family includes four isoforms (KCC1-4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K(+) and Cl(-) with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2-4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na(+)-K(+)-2Cl(-)-cotransport inhibitor (bumetanide) dose-dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves from KCC3(-/-) mice than in nerves from wild-type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild-type strains. KCC3(-/-) mice also manifested a prominent motor deficit in the beam-walking test. This is the first study to demonstrate that the K(+)-Cl(-) cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves. (c) 2010 Wiley-Liss, Inc.

Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

NASA Astrophysics Data System (ADS)

Donoghue, John P.; Sanes, Jerome N.

1987-02-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

[Scalp neuralgia and headache elicited by cranial superficial anatomical causes: supraorbital neuralgia, occipital neuralgia, and post-craniotomy headache].

PubMed

Shimizu, Satoru

2014-01-01

Most scalp neuralgias are supraorbital or occipital. Although they have been considered idiopathic, recent studies revealed that some were attributable to mechanical irritation with the peripheral nerve of the scalp by superficial anatomical cranial structures. Supraorbital neuralgia involves entrapment of the supraorbital nerve by the facial muscle, and occipital neuralgia involves entrapment of occipital nerves, mainly the greater occipital nerve, by the semispinalis capitis muscle. Contact between the occipital artery and the greater occipital nerve in the scalp may also be causative. Decompression surgery to address these neuralgias has been reported. As headache after craniotomy is the result of iatrogenic injury to the peripheral nerve of the scalp, post-craniotomy headache should be considered as a differential diagnosis.

Properties of slow- and fast-twitch muscle fibres in a mouse model of amyotrophic lateral sclerosis.

PubMed

Atkin, Julie D; Scott, Rachel L; West, Jan M; Lopes, Elizabeth; Quah, Alvin K J; Cheema, Surindar S

2005-05-01

This investigation was undertaken to determine if there are altered histological, pathological and contractile properties in presymptomatic or endstage diseased muscle fibres from representative slow-twitch and fast-twitch muscles of SOD1 G93A mice in comparison to wildtype mice. In presymptomatic SOD1 G93A mice, there was no detectable peripheral dysfunction, providing evidence that muscle pathology is secondary to motor neuronal dysfunction. At disease endstage however, single muscle fibre contractile analysis demonstrated that fast-twitch muscle fibres and neuromuscular junctions are preferentially affected by amyotrophic lateral sclerosis-induced denervation, being unable to produce the same levels of force when activated by calcium as muscle fibres from their age-matched controls. The levels of transgenic SOD1 expression, aggregation state and activity were also examined in these muscles but there no was no preference for muscle fibre type. Hence, there is no simple correlation between SOD1 protein expression/activity, and muscle fibre type vulnerability in SOD1 G93A mice.

Increasing expression and decreasing degradation of SMN ameliorate the spinal muscular atrophy phenotype in mice

PubMed Central

Kwon, Deborah Y.; Motley, William W.; Fischbeck, Kenneth H.; Burnett, Barrington G.

2011-01-01

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by reduced levels of the survival motor neuron (SMN) protein. Here we show that the proteasome inhibitor, bortezomib, increases SMN in cultured cells and in peripheral tissues of SMA model mice. Bortezomib-treated animals had improved motor function, which was associated with reduced spinal cord and muscle pathology and improved neuromuscular junction size, but no change in survival. Combining bortezomib with the histone deacetylase inhibitor trichostatin A (TSA) resulted in a synergistic increase in SMN protein levels in mouse tissue and extended survival of SMA mice more than TSA alone. Our results demonstrate that a combined regimen of drugs that decrease SMN protein degradation and increase SMN gene transcription synergistically increases SMN levels and improves the lifespan of SMA model mice. Moreover, this study indicates that while increasing SMN levels in the central nervous system may help extend survival, peripheral tissues can also be targeted to improve the SMA disease phenotype. PMID:21693563

Intramuscular renin-angiotensin system is activated in human muscular dystrophy.

PubMed

Sun, Guilian; Haginoya, Kazuhiro; Dai, Hongmei; Chiba, Yoko; Uematsu, Mitsugu; Hino-Fukuyo, Naomi; Onuma, Akira; Iinuma, Kazuie; Tsuchiya, Shigeru

2009-05-15

To investigate the role of the muscular renin-angiotensin system (RAS) in human muscular dystrophy, we used immunohistochemistry and Western blotting to examine the cellular localization of angiotensin-converting enzyme (ACE), the angiotensin II type 1 receptor (AT1) and the angiotensin II type 2 receptor (AT2) in muscle biopsies from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy (CMD). In normal muscle, ACE was expressed in vascular endothelial cells and neuromuscular junctions (NMJs), whereas AT1 was immunolocalized to the smooth muscle cells of blood vessels and intramuscular nerve twigs. AT2 was immunolocalized in the smooth muscle cells of blood vessels. These findings suggest that the RAS has a functional role in peripheral nerves and NMJs. ACE and AT1, but AT2 immunoreactivity were increased markedly in dystrophic muscle as compared to controls. ACE and the AT1 were strongly expressed in the cytoplasm and nuclei of regenerating muscle fibers, fibroblasts, and in macrophages infiltrating necrotic fibers. Double immunolabeling revealed that activated fibroblasts in the endomysium and perimysium of DMD and CMD muscle were positive for ACE and AT1. Triple immunolabeling demonstrated that transforming growth factor-beta1 (TGF-beta1) and ACE were colocalized on the cytoplasm of activated fibroblasts in dystrophic muscle. Furthermore, Western blotting showed increases in the expression of AT1 and TGF-beta1 protein in dystrophic muscle, which coincided with our immunohistochemical results. The overexpression of ACE and AT1 in dystrophic muscle would likely result in the increased production of Ang II, which may act on these cells in an autocrine manner via AT1. The activation of AT1 may induce fibrous tissue formation through overexpression of TGF-beta1, which potently activates fibrogenesis and suppresses regeneration. In conclusion, our results imply that the intramuscular RAS-TGF-beta1 pathway is activated in human muscular dystrophy and plays a role at least partly in the pathophysiology of this disease.

Autonomic control of body temperature and blood pressure: influences of female sex hormones.

PubMed

Charkoudian, Nisha; Hart, Emma C J; Barnes, Jill N; Joyner, Michael J

2017-06-01

Female reproductive hormones exert important non-reproductive influences on autonomic regulation of body temperature and blood pressure. Estradiol and progesterone influence thermoregulation both centrally and peripherally, where estradiol tends to promote heat dissipation, and progesterone tends to promote heat conservation and higher body temperatures. Changes in thermoregulation over the course of the menstrual cycle and with hot flashes at menopause are mediated by hormonal influences on neural control of skin blood flow and sweating. The influence of estradiol is to promote vasodilation, which, in the skin, results in greater heat dissipation. In the context of blood pressure regulation, both central and peripheral hormonal influences are important as well. Peripherally, the vasodilator influence of estradiol contributes to the lower blood pressures and smaller risk of hypertension seen in young women compared to young men. This is in part due to a mechanism by which estradiol augments beta-adrenergic receptor mediated vasodilation, offsetting alpha-adrenergic vasoconstriction, and resulting in a weak relationship between muscle sympathetic nerve activity and total peripheral resistance, and between muscle sympathetic nerve activity and blood pressure. After menopause, with the loss of reproductive hormones, sympathetic nerve activity, peripheral resistance and blood pressure become more strongly related, and sympathetic nerve activity (which increases with age) becomes a more important contributor to the prevailing level of blood pressure. Continuing to increase our understanding of sex hormone influences on body temperature and blood pressure regulation will provide important insight for optimization of individualized health care for future generations of women.

Magnetic stimulation of the upper trapezius muscles in patients with migraine - A pilot study.

PubMed

Sollmann, Nico; Trepte-Freisleder, Florian; Albers, Lucia; Jung, Nikolai H; Mall, Volker; Meyer, Bernhard; Heinen, Florian; Krieg, Sandro M; Landgraf, Mirjam N

2016-11-01

Repetitive peripheral magnetic stimulation (rPMS) has been applied to musculoskeletal pain conditions. Since recent data show that migraine and tension-type headache (TTH) might be closely related to peripheral muscular pain in the neck and shoulder region (supporting the concept of the trigemino-cervical complex (TCC)), this pilot study explores the acceptance of rPMS to the upper trapezius muscles in migraine (partly in combination with TTH). We used rPMS to stimulate active myofascial trigger points (aTrPs) of the upper trapezius muscles in 20 young adults suffering from migraine. Acceptance was assessed by a standardized questionnaire, whereas self-rated effectiveness was evaluated by headache calendars and the Migraine Disability Assessment (MIDAS). Algometry was performed to explore the local effect of rPMS on the muscles. Acceptance of rPMS was shown in all subjects without any adverse events, and rPMS had a statistically significant impact on almost every parameter of the headache calendar and MIDAS. Among others, the number of migraine attacks (p < 0.001) and migraine intensity (p = 0.001) significantly decreased regarding pre- and post-stimulation assessments. Accordingly, 100.0% of subjects would repeat the stimulation, while 90.0% would recommend rPMS as a treatment option for migraine. rPMS might represent a promising tool to alleviate migraine symptoms within the context of myofascial pain. This might be due to stimulation-dependent modulation of the peripheral sensory effect within the TCC in migraine. However, sham-controlled studies with larger and more homogeneous cohorts are needed to prove a potential beneficial effect. Ethics Committee Registration Numbers: 356-14 and 447/14. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Nerve-muscle interactions during flight muscle development in Drosophila

NASA Technical Reports Server (NTRS)

Fernandes, J. J.; Keshishian, H.

1998-01-01

During Drosophila pupal metamorphosis, the motoneurons and muscles differentiate synchronously, providing an opportunity for extensive intercellular regulation during synapse formation. We examined the existence of such interactions by developmentally delaying or permanently eliminating synaptic partners during the formation of indirect flight muscles. When we experimentally delayed muscle development, we found that although adult-specific primary motoneuron branching still occurred, the higher order (synaptic) branching was suspended until the delayed muscle fibers reached a favourable developmental state. In reciprocal experiments we found that denervation caused a decrease in the myoblast pool. Furthermore, the formation of certain muscle fibers (dorsoventral muscles) was specifically blocked. Exceptions were the adult muscles that use larval muscle fibers as myoblast fusion targets (dorsal longitudinal muscles). However, when these muscles were experimentally compelled to develop without their larval precursors, they showed an absolute dependence on the motoneurons for their formation. These data show that the size of the myoblast pool and early events in fiber formation depend on the presence of the nerve, and that, conversely, peripheral arbor development and synaptogenesis is closely synchronized with the developmental state of the muscle.

A Rare Case of Chronic Active Epstein-Barr Virus (EBV) Infection Accompanied by the Infiltration of EBV-infected CD8+ T Cells into the Muscle.

PubMed

Kobayashi, Nobuhiko; Mitsui, Takeki; Ogawa, Yoshiyuki; Iriuchishima, Hirono; Takizawa, Makiko; Yokohama, Akihiko; Saitoh, Takayuki; Koiso, Hiromi; Tsukamoto, Norifumi; Murakami, Hirokazu; Nojima, Yoshihisa; Handa, Hiroshi

2018-04-01

We describe a rare case of chronic active Epstein-Barr virus (CAEBV) infection, with infiltration of the skeletal muscle. A 19-year-old woman with swollen cervical lymph nodes and a fever was referred to our hospital. Swelling of the trapezium muscle and elevation of creatinine kinase level were observed. Biopsy results of the brachialis muscle revealed infiltration of Epstein-Barr virus (EBV)-encoded RNA-positive CD8 T lymphocytes. The EBV virus load in the peripheral blood was high, and EBV monoclonality was determined by Southern blot analysis. Owing to the rarity of CAEBV with skeletal muscle infiltration, this case alerts physicians to the potential diagnostic pitfalls of CAEBV.

Low circulating levels of IGF-1 in healthy adults are associated with reduced β-cell function, increased intramyocellular lipid, and enhanced fat utilization during fasting.

PubMed

Thankamony, Ajay; Capalbo, Donatella; Marcovecchio, M Loredana; Sleigh, Alison; Jørgensen, Sine Wanda; Hill, Nathan R; Mooslehner, Katrin; Yeo, Giles S H; Bluck, Les; Juul, Anders; Vaag, Allan; Dunger, David B

2014-06-01

Low serum IGF-1 levels have been linked to increased risk for development of type 2 diabetes. However, the physiological role of IGF-1 in glucose metabolism is not well characterized. Our objective was to explore glucose and lipid metabolism associated with variations in serum IGF-1 levels. IGF-1 levels were measured in healthy, nonobese male volunteers aged 18 to 50 years from a biobank (n = 275) to select 24 subjects (age 34.8 ± 8.9 years), 12 each in the lowest (low-IGF) and highest (high-IGF) quartiles of age-specific IGF-1 SD scores. Evaluations were undertaken after a 24-hour fast and included glucose and glycerol turnover rates using tracers, iv glucose tolerance test to estimate peripheral insulin sensitivity (IS) and acute insulin and C-peptide responses (indices of insulin secretion), magnetic resonance spectroscopy to measure intramyocellular lipids (IMCLs), calorimetry, and gene expression studies in a muscle biopsy. Acute insulin and C-peptide responses, IS, and glucose and glycerol rate of appearance (Ra) were evaluated. Fasting insulin and C-peptide levels and glucose Ra were reduced (all P < .05) in low-IGF compared with high-IGF subjects, indicating increased hepatic IS. Acute insulin and C-peptide responses were lower (both P < .05), but similar peripheral IS resulted in reduced insulin secretion adjusted for IS in low-IGF subjects (P = 0.044). Low-IGF subjects had higher overnight levels of free fatty acids (P = .028) and β-hydroxybutyrate (P = .014), increased accumulation of IMCLs in tibialis anterior muscle (P = .008), and a tendency for elevated fat oxidation rates (P = .058); however, glycerol Ra values were similar. Gene expression of the fatty acid metabolism pathway (P = .0014) was upregulated, whereas the GLUT1 gene was downregulated (P = .005) in the skeletal muscle in low-IGF subjects. These data suggest that serum IGF-1 levels could be an important marker of β-cell function and glucose as well as lipid metabolic responses during fasting.

Evolutionary anatomy of the muscular apparatus involved in the anchoring of Acanthocephala to the intestinal wall of their vertebrate hosts.

PubMed

Herlyn, Holger; Taraschewski, Horst

2017-04-01

Different conceptions exist regarding structure, function, and evolution of the muscles that move the acanthocephalan presoma, including the proboscis, i.e., the usually hooked hold-fast anchoring these endoparasites to the intestinal wall of their vertebrate definitive hosts. In order to clarify the unresolved issues, we carried out a light microscopic analysis of series of semi-thin sections and whole mounts representing the three traditional acanthocephalan classes: Archiacanthocephala (Macracanthorhynchus hirudinaceus), Eoacanthocephala (Paratenuisentis ambiguus, Tenuisentis niloticus), and Palaeacanthocephala (Acanthocephalus anguillae, Echinorhynchus truttae, Pomphorhynchus laevis, Corynosoma sp.). Combining our data with published light, transmission electron, and scanning electron microscopic data, we demonstrate that receptacle protrusor and proboscis receptacle in Archi- and Eoacanthocephala are homologous to the outer and inner wall of the proboscis receptacle in Palaeacanthocephala. Besides the proboscis receptacle and a "surrounding muscle," the last common ancestor of Acanthocephala presumably possessed a proboscis retractor, receptacle retractor, neck retractor (continuous with lemnisci compressors), and retinacula. These muscles most probably evolved in the acanthocephalan stem line. Moreover, the last common ancestor of Acanthocephala presumably possessed only a single layer of muscular cords under the presomal tegument while the metasomal body wall had circular and longitudinal strands. Two lateral receptacle flexors (also lateral receptacle protrusors), an apical muscle plate (surrounding one or two apical sensory organs), a midventral longitudinal muscle, and the differentiation of longitudinal body wall musculature at the base of the proboscis probably emerged within Archiacanthocephala. All muscles have a common organization principle: a peripheral layer of contractile filaments encloses the cytoplasm.

Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity

PubMed Central

Matsui, Takashi; Omuro, Hideki; Liu, Yu-Fan; Soya, Mariko; Shima, Takeru; McEwen, Bruce S.; Soya, Hideaki

2017-01-01

Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresis-mass spectrometry–based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxy-cinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain. PMID:28515312

Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity.

PubMed

Matsui, Takashi; Omuro, Hideki; Liu, Yu-Fan; Soya, Mariko; Shima, Takeru; McEwen, Bruce S; Soya, Hideaki

2017-06-13

Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresis-mass spectrometry-based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxy-cinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain.

Isokinetic and Electromyographic Properties of Muscular Endurance in Short and Long-Term Type 2 Diabetes

PubMed Central

Hatef, Boshra; Ghanjal, Ali; Meftahi, Gholam Hossein; Askary-Ashtiani, Ahmadreza

2016-01-01

Background: Patients with type 2 diabetes mellitus (T2DM) are subject to progressive reduction of muscle mass and strength. The aim of this study was to assess muscle forces and electromyography (EMG) indices in short and long-term diabetes during an isokinetic exercise. Methods: The peak torque, work, mean power frequency (MPF) and root mean square (RMS) of knee flexors and extensors during 40 isokinetic knee extension-flexion repetitions with a velocity of 150 degree/s were recorded. 18 patients with less than 10 years with T2DM and 12 patients with equal and more than 10 years of disease were compared with 20 gender, body mass index, physical activity and peripheral circulation matched healthy controls. Results: The fatigue index and slope of line across the peak torque values of the knee flexor indicate that patients with long-term T2DM were significantly more resistant to fatigue in comparison with the two other groups (p<0.009). Whereas the MPF decrease during isokinetic protocol interact with grouping in the medial hamstring (p<0.042), but it was independent to groups in other muscles (p<0.0001). The increase of RMS after fatigue protocol interacted with sex for the medial hamstring and vastus lateralis (p<0.039) and interacted with group for the extensor muscles (p<0.045). Discussion & Conclusion: It seems that long-term T2DM cause some neuromuscular adaptations to maintain knee flexor muscle performance during functional activity especially postural control. PMID:27045412

38 CFR 4.45 - The joints.

Code of Federal Regulations, 2013 CFR

2013-07-01

... movement (due to muscle injury, disease or injury of peripheral nerves, divided or lengthened tendons, etc... the purpose of rating disability from arthritis, the shoulder, elbow, wrist, hip, knee, and ankle are...

38 CFR 4.45 - The joints.

Code of Federal Regulations, 2012 CFR

2012-07-01

... movement (due to muscle injury, disease or injury of peripheral nerves, divided or lengthened tendons, etc... the purpose of rating disability from arthritis, the shoulder, elbow, wrist, hip, knee, and ankle are...

38 CFR 4.45 - The joints.

Code of Federal Regulations, 2011 CFR

2011-07-01

... movement (due to muscle injury, disease or injury of peripheral nerves, divided or lengthened tendons, etc... the purpose of rating disability from arthritis, the shoulder, elbow, wrist, hip, knee, and ankle are...

38 CFR 4.45 - The joints.

Code of Federal Regulations, 2014 CFR

2014-07-01

... movement (due to muscle injury, disease or injury of peripheral nerves, divided or lengthened tendons, etc... the purpose of rating disability from arthritis, the shoulder, elbow, wrist, hip, knee, and ankle are...

Blood pressure and calf muscle oxygen extraction during plantar flexion exercise in peripheral artery disease.

PubMed

Luck, J Carter; Miller, Amanda J; Aziz, Faisal; Radtka, John F; Proctor, David N; Leuenberger, Urs A; Sinoway, Lawrence I; Muller, Matthew D

2017-07-01

Peripheral artery disease (PAD) is an atherosclerotic vascular disease that affects 200 million people worldwide. Although PAD primarily affects large arteries, it is also associated with microvascular dysfunction, an exaggerated blood pressure (BP) response to exercise, and high cardiovascular mortality. We hypothesized that fatiguing plantar flexion exercise that evokes claudication elicits a greater reduction in skeletal muscle oxygenation (SmO 2 ) and a higher rise in BP in PAD compared with age-matched healthy subjects, but low-intensity steady-state plantar flexion elicits similar responses between groups. In the first experiment, eight patients with PAD and eight healthy controls performed fatiguing plantar flexion exercise (from 0.5 to 7 kg for up to 14 min). In the second experiment, seven patients with PAD and seven healthy controls performed low-intensity plantar flexion exercise (2.0 kg for 14 min). BP, heart rate (HR), and SmO 2 were measured continuously using near-infrared spectroscopy (NIRS). SmO 2 is the ratio of oxygenated hemoglobin to total hemoglobin, expressed as a percent. At fatigue, patients with PAD had a greater increase in mean arterial BP (18 ± 2 vs. vs. 10 ± 2 mmHg, P = 0.029) and HR (14 ± 2 vs. 6 ± 2 beats/min, P = 0.033) and a greater reduction in SmO 2 (-54 ± 10 vs. -12 ± 4%, P = 0.001). However, both groups had similar physiological responses to low-intensity, nonpainful plantar flexion exercise. These data suggest that patients with PAD have altered oxygen uptake and/or utilization during fatiguing exercise coincident with an augmented BP response. NEW & NOTEWORTHY In this laboratory study, patients with peripheral artery disease performed plantar flexion exercise in the supine posture until symptoms of claudication occurred. Relative to age- and sex-matched healthy subjects we found that patients had a higher blood pressure response, a higher heart rate response, and a greater reduction in skeletal muscle oxygenation as determined by near-infrared spectroscopy. Our data suggest that muscle ischemia contributes to the augmented exercise pressor reflex in peripheral artery disease. Copyright © 2017 the American Physiological Society.

Methylene Blue Partially Rescues Heart Defects in a Drosophila Model of Huntington's Disease.

PubMed

Heidari, Raheleh; Monnier, Véronique; Martin, Elodie; Tricoire, Hervé

2015-01-01

Huntington's disease (HD) is a Polyglutamine disease caused by the presence of CAG repeats in the first exon of Huntingtin (Htt), a large protein with multiple functions. In addition to neurodegeneration of specific brain regions, notably the striatum, HD also shows alterations in peripheral tissues, such as the heart, skeletal muscles or peripheral endocrine glands. Mutant Huntingtin (mHtt)-driven mitochondrial impairment may underlie some of the CNS and peripheral tissues dysfunctions, especially in tissues with high energy demand such as the heart. The aim of this study is to characterize two new inducible Drosophila HD heart models and to assay the therapeutic potential of methylene blue in these HD models. We report the construction of inducible Drosophila HD heart models, expressing two Nter fragments of the protein encompassing either exon 1 or the first 171 amino acids and the characterization of heart phenotypes in vivo. We show that both mHtt fragments are able to impair fly cardiac function with different characteristics. Additionally, expression of mHtt, which was limited to adulthood only, leads to mild heart impairment, as opposed to a strong and age-dependent phenotype observed when mHtt expression was driven during both developmental and adult stages. We report that treatment with methylene blue (MB), a protective compound in mitochondria-related diseases, partially protects the fly's heart against mHtt-induced toxicity, but does not rescue neuronal or glial phenotypes in other fly models of HD. This may be linked to its low penetration through the fly's blood-brain barrier. Our data suggest that improvement of mitochondrial function by MB, or related compounds, could be an efficient therapeutic strategy to prevent cardiac failure in HD patients.