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Sarcopenia, the progressive loss of muscle mass and function, universally affects older adults and is closely associated with frailty and reduced quality of life. Despite the inevitable consequences of sarcopenia and its relevance to healthspan, no pharmacological therapies are currently available. Ghrelin is a gut‐released hormone that increases appetite and body weight through acylation. Acylated ghrelin activates its receptor, growth hormone secretagogue receptor 1a (GHSR1a), in the brain by binding to it. Studies have demonstrated that acyl and unacylated ghrelin (UnAG) both have protective effects against acute pathological conditions independent of receptor activation. Here, we investigated the long‐term effects of UnAG in age‐associated muscle atrophy and contractile dysfunction in mice. Four‐month‐old and 18‐month‐old mice were subjected to either UnAG or control treatment for 10 months. UnAG did not affect food consumption or body weight. Gastrocnemius and quadriceps muscle weights were reduced by 20%–30% with age, which was partially protected against by UnAG. Specific force, force per cross‐sectional area, measured in isolated extensor digitorum longus muscle was diminished by 30% in old mice; however, UnAG prevented the loss of specific force. UnAG also protected from decreases in mitochondrial respiration and increases in hydrogen peroxide generation of skeletal muscle of old mice. Results of bulk mRNA‐seq analysis and our contractile function data show that UnAG reversed neuromuscular junction impairment that occurs with age. Collectively, our data revealed the direct role of UnAG in mitigating sarcopenia in mice, independent of food consumption or body weight, implicating UnAG treatment as a potential therapy against sarcopenia. [ABSTRACT FROM AUTHOR]

Peripheral nerve damage is a critical disorder causing disability of locomotion. The aim of the study was to clarify the effects of testosterone and tacrolimus on the gastrocnemius muscle following sciatic injury. The study was done on 20 rats (n = 5 in each group) whose left sciatic nerve was crushed for 10 s. The sham group (S) of animals received no medicine; the testosterone group (Tes) received testosterone (5 mg/kg, s.c.); the tacrolimus group (Tac): received tacrolimus (5 mg/kg, p.o.); the testosterone and tacrolimus group (Tes+Tac) received testosterone (5 mg/kg, s.c.) and tacrolimus (5 mg/kg, p.o.) daily for four weeks. The gastrocnemius was assessed by gross observation of the plantar surface of paws; the pelvic limb mass muscle and the muscle diameter ratio of the left pelvic limb to the right one by ultrasonography. The gastrocnemius muscle index (GMI) of the left and right pelvic limb, muscle colour, and pathologic changes were also studied. Pathology study of the gastrocnemius included fatty infiltration, muscle atrophy, presence of inflammatory cells and fibrosis formation. Heel redness and swelling were seen in group Tac. No significant difference was found in the GMI between the Tes and S groups (P > 0.01); its value was higher than in the Tes+Tac and Tac groups (P < 0.01). One rat in group Tes had fatty infiltration grade II. Inflammatory cells were grade I in group Tes but fibrosis formation was grade I in group Tes+Tac. Our results show that tacrolimus and testosterone administration may shorten sciatic nerve regeneration time. Testosterone may diminish gastrocnemius muscle atrophy after sciatic nerve crush. [ABSTRACT FROM AUTHOR]

Synaptopodin-2 (SYNPO2) is a protein associated with the Z-disc in striated muscle cells. It interacts with α-actinin and filamin C, playing a role in Z-disc maintenance under stress by chaperone-assisted selective autophagy (CASA). In smooth muscle cells, SYNPO2 is a component of dense bodies. Furthermore, it has been proposed to play a role in tumor cell proliferation and metastasis in many different kinds of cancers. Alternative transcription start sites and alternative splicing predict the expression of six putative SYNPO2 isoforms differing by extended amino- and/or carboxy-termini. Our analyses at mRNA and protein levels revealed differential expression of SYNPO2 isoforms in cardiac, skeletal and smooth muscle cells. We identified synemin, an intermediate filament protein, as a novel binding partner of the PDZ-domain in the amino-terminal extension of the isoforms mainly expressed in cardiac and smooth muscle cells, and demonstrated colocalization of SYNPO2 and synemin in both cell types. A carboxy-terminal extension, mainly expressed in smooth muscle cells, is sufficient for association with dense bodies and interacts with α-actinin. SYNPO2 therefore represents an additional and novel link between intermediate filaments and the Z-discs in cardiomyocytes and dense bodies in smooth muscle cells, respectively. In pathological skeletal muscle samples, we identified SYNPO2 in the central and intermediate zones of target fibers of patients with neurogenic muscular atrophy, and in nemaline bodies. Our findings help to understand distinct functions of individual SYNPO2 isoforms in different muscle tissues, but also in tumor pathology. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is a heritable neuromuscular disorder which encompasses a large group of genetic disorders characterized by slowly progressive degeneration of lower motor neurons. The mutation is seen in the SMN1 gene mapped on chromosome 5. Depending on the age of the onset and the degree of severity, SMA has three subtypes. We discuss the autopsy findings in a case of Type 1 SMA also known by the name Werdnig-Hoffmann disease, to highlight the primary changes in the spinal cord, and skeletal muscle with association changes in the liver and terminal respiratory complications.

Spinal muscular atrophy (SMA) encompasses a group of disorders with loss of spinal motor neurons.The report describes the neuropathological findings including brain and spinal cord at autopsy in a five-and-half-month-old boy with suspected type 1 SMA. The anterior motor neurons, Clarke's column at all the levels of spinal cord showed neuronal loss and degeneration while neurons at all the deep grey nuclei were preserved apart from variable degree anoxic changes. Skeletal muscle biopsy revealed features of neurogenic atrophy consistent with SMA. A differential diagnosis like storage disorders was excluded using electron microscopy. No extra-neural manifestations were seen. Neuropathological features at autopsy have seldom been reported in the literature. [ABSTRACT FROM AUTHOR]

Synaptopodin-2 (SYNPO2) is a protein associated with the Z-disc in striated muscle cells. It interacts with α-actinin and filamin C, playing a role in Z-disc maintenance under stress by chaperone-assisted selective autophagy (CASA). In smooth muscle cells, SYNPO2 is a component of dense bodies. Furthermore, it has been proposed to play a role in tumor cell proliferation and metastasis in many different kinds of cancers. Alternative transcription start sites and alternative splicing predict the expression of six putative SYNPO2 isoforms differing by extended amino- and/or carboxy-termini. Our analyses at mRNA and protein levels revealed differential expression of SYNPO2 isoforms in cardiac, skeletal and smooth muscle cells. We identified synemin, an intermediate filament protein, as a novel binding partner of the PDZ-domain in the amino-terminal extension of the isoforms mainly expressed in cardiac and smooth muscle cells, and demonstrated colocalization of SYNPO2 and synemin in both cell types. A carboxy-terminal extension, mainly expressed in smooth muscle cells, is sufficient for association with dense bodies and interacts with α-actinin. SYNPO2 therefore represents an additional and novel link between intermediate filaments and the Z-discs in cardiomyocytes and dense bodies in smooth muscle cells, respectively. In pathological skeletal muscle samples, we identified SYNPO2 in the central and intermediate zones of target fibers of patients with neurogenic muscular atrophy, and in nemaline bodies. Our findings help to understand distinct functions of individual SYNPO2 isoforms in different muscle tissues, but also in tumor pathology.

The therapeutic effect of three polyvinyl alcohol (PVA) membranes loaded with electrically conductive materials - carbon nanotubes ( PVA-CNTs) and polypyrrole ( PVA-PPy) - were tested in vivo for neuro-muscular regeneration after an axonotmesis injury in the rat sciatic nerve. The membranes electrical conductivity measured was 1.5 ± 0.5 × 10−6 S/m, 579 ± 0.6 × 10−6 S/m, and 1837.5 ± 0.7 × 10−6 S/m, respectively. At week-12, a residual motor and nociceptive deficit were present in all treated groups, but at week-12, a better recovery to normal gait pattern of the PVA-CNTs and PVA-PPy treated groups was observed. Morphometrical analysis demonstrated that PVA-CNTs group presented higher myelin thickness and lower g-ratio. The tibialis anterior muscle, in the PVA-PPy and PVA-CNTs groups showed a 9% and 19% increase of average fiber size area and a 5% and 10% increase of the 'minimal Feret's diameter,' respectively. No inflammation, degeneration, fibrosis or necrosis were detected in lung, liver, kidneys, spleen, and regional lymph nodes and absence of carbon deposits was confirmed with Von Kossa and Masson-Fontana stains. In conclusion, the membranes of PVA-CNTs and PVA-PPy are biocompatible and have electrical conductivity. The higher electrical conductivity measured in PVA-CNTs membrane might be responsible for the positive results on maturation of myelinated fibers. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1267-1280, 2017. [ABSTRACT FROM AUTHOR]

Introduction: Botulinum toxin A (BoNTA) is routine treatment for hypertonicity in children with cerebral palsy (CP).Methods: This single-blind, prospective, cross-sectional study of 10 participants (mean age 11 years 7 months) was done to determine the relationship between muscle histopathology and BoNTA in treated medial gastrocnemius muscle of children with CP. Open muscle biopsies were taken from medial gastrocnemius muscle and vastus lateralis (control) during orthopedic surgery.Results: Neurogenic atrophy in the medial gastrocnemius was seen in 6 participants between 4 months and 3 years post-BoNTA. Type 1 fiber loss with type 2 fiber predominance was significantly related to the number of BoNTA injections (r = 0.89, P < 0.001).Conclusions: The impact of these changes in muscle morphology on muscle function in CP is not clear. It is important to consider rotating muscle selection or injection sites within the muscle or allowing longer time between injections. [ABSTRACT FROM AUTHOR]

Spinal nerve L5/L6 ligation (SNL) in rats has become the standard for mechanistic studies of peripheral neuropathy and screening for novel analgesics. Conventional SNL in our hybrid mice resulted in a wide range of allodynia. Anatomical evaluation indicated that a variable number of lumbar vertebrae existed, resulting in L4/L5 or L5/L6 being ligated. Surprisingly, L4/L5 ligation did not result in ipsilateral hind limb paralysis and produced robust allodynia. Following a recent report that the mouse L4 neural segment is homologous with rat L5 we generated L4, L5 or both L4 and L5 (L4/L5) ligations in C57 mice after establishing a modified set of surgical landmarks. In contrast to rats, L4 ligation in these mice did not result in hind limb paralysis. Robust allodynia was observed in all three ligation groups. Nerve degeneration confirmed that L4 and L5, respectively, are primary contributors to the tibial and sural branches of the sciatic nerve in mice. A larger von Frey sensitive area reflected the wider distribution of Wallerian degeneration in the hindlimb of L4- compared to L5-ligated mice. Ligation of mouse L4 and L5 spinal nerves produces consistent, robust neuropathic pain behaviors and is suitable as a model for investigating mechanisms of neuropathic pain and for testing of novel analgesics. Gabapentin, used as a validation drug in neuropathic pain models and as a reference compound for novel analgesics, significantly reduced allodynia in the mice tested (L4/L5 ligations). Given the ease of surgery, robust allodynia, and larger von Frey sensitive area, we conclude that combined ligation of spinal nerves L4 and L5 optimizes the SNL model in mice. [ABSTRACT FROM AUTHOR]

Recurrent laryngeal neuropathy (RLN, laryngeal hemiplegia, laryngeal paralysis, 'roaring') is common in the equine industry with a prevalence ranging from 2.6-11% in light breeds (Raphel 1982; Lane 1987; Morris and Seeherman 1990) up to 38% in draught breeds (Brakenhoff et al. 2006; Perkins et al. 2009). There are a number of different surgical treatments currently available and more being developed. This article aims to discuss factors affecting choice of treatment and then provide an evidence-based approach to describe surgical approaches, success rates and morbidity. Specific details of surgical methods are not given as they are readily available in surgical textbooks (Stick 2006; McGorum et al. 2007). [ABSTRACT FROM AUTHOR]

Introduction: Brachial diplegia is a clinical term used to describe weakness restricted to the upper extremities. We report a case of brachial diplegia associated with West Nile virus infection. Methods: A 48-year-old man developed severe painless bilateral upper extremity weakness within a few weeks of a flu-like illness. Results: Clinical examination revealed marked periscapular, shoulder girdle, and humeral muscle atrophy and bilateral scapular winging, with near symmetrical bilateral hypotonic upper extremity weakness. This was associated with clinical signs of an encephalomyelopathy without cognitive or sensory deficits. Electrophysiological studies demonstrated a subacute disorder of motor neurons, their axons or both, involving the cervical and thoracic myotomes, with ongoing denervation. Serological studies confirmed recent West Nile virus (WNV) infection. Gradual improvement occurred following conservative supportive therapies. Conclusions: Progressive brachial diplegia is a rare neuromuscular presentation of WNV neuroinvasive disease. This case report adds to the clinical spectrum of WNV-induced neurologic sequelae. Muscle Nerve 45: 900-904, 2012 [ABSTRACT FROM AUTHOR]

A child is reported with Behcet's disease who presented with skin and joint manifestations, oral ulcers, brainstem syndrome and neurogenic muscular atrophy. The neurogenic muscular atrophy was confirmed by electrophysiologic, histologic and histochemical studies. Electron microscopy of muscle showed a vasculopathy. The possible etiology of the muscle lesions is discussed. The relevant literature on muscle and peripheral nerve involvement in Behcet's disease is reviewed. It is proposed that neuromyopathy be added to the neurological manifestations of Behcet's disease. To our knowledge, this is the first case of neurogenic atrophy reported in Behcet's disease. [ABSTRACT FROM AUTHOR]

Copyright of Italian Journal of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Carnitine level and carnitine palmityl transferase (CPT) activity were investigated in muscles of patients with infantile and juvenile spinal muscular atrophy and polyneuropathies. A significant decrease of both carnitine and CPT was found in the infantile spinal muscular atrophy, but not in the other neurogenic muscle atrophies. These findings were compared with the experimental effect of denervation and reinnervation upon the lipid metabolism in soleus and extensor digitorum longus (EDL) of adult and newborn rats. Twenty-one days after denervation free and total carnitine decreased significantly in both EDL ( P<0.001) and soleus ( P<0.05) of adult animals. CPT activity was significantly decreased in the soleus 50 days after denervation ( P<0.005). Long-term reinnervation restored the level of carnitine fraction and CPT activity. l-carnitine treatment for 21 days restored the level of free carnitine to normal in the soleus of denervated adult animals. Denervation in newborn rats influenced carnitine concentration in soleus and EDL to a lesser extent; the treatment with l-carnitine raised short-chain acylcarnitines in denervated muscles, while reinnervation restored carnitine level within 50 days. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Neurology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Neurogenic atrophy refers to the loss of muscle mass and function that results directly from injury or disease of the peripheral nervous system. Individuals with neurogenic atrophy may experience reduced functional status and quality of life and, in some circumstances, reduced survival. Distinct pathological findings on muscle histology can aid in diagnosis of a neurogenic cause for muscle dysfunction, and provide indicators for the chronicity of denervation. Denervation induces pleiotypic responses in skeletal muscle, and the molecular mechanisms underlying neurogenic muscle atrophy appear to share common features with other causes of muscle atrophy, including activation of FOXO transcription factors and corresponding induction of ubiquitin-proteasomal and lysosomal degradation. In this review, we provide an overview of histologic features of neurogenic atrophy and a summary of current understanding of underlying mechanisms. [ABSTRACT FROM AUTHOR]

Competence in muscle biopsy evaluation is a core component of neuropathology practice. The practicing neuropathologist should be able to prepare frozen sections of muscle biopsies with minimal artifacts and identify key histopathologic features of neuromuscular disease in hematoxylin and eosin-stained sections as well as implement and interpret a basic panel of additional histochemical, enzyme histochemical, and immunohistochemical stains. Important to everyday practice is a working knowledge of normal muscle histology at different ages, muscle motor units, pitfalls of myotendinous junctions, nonpathologic variations encountered at traditional and nontraditional muscle sites, the pathophysiology of myonecrosis and regeneration, and approaches to distinguish muscular dystrophies from inflammatory myopathies and other necrotizing myopathies. Here, we provide a brief overview of what every neuropathologist needs to know concerning the muscle biopsy., (© 2020 American Association of Neuropathologists, Inc.)