OBJECTIVE: To determine the location of the motor endplate zones (MoEPs) for the three heads of the triceps brachii muscles during cadaveric dissection and estimate the safe injection zone using ultrasonography.METHODS: We studied 12 upper limbs of 6 fresh cadavers obtained from body donations to the medical school anatomy institution in Seoul, Korea. The locations of MoEPs were expressed as the percentage ratio of the vertical distance from the posterior acromion angle to the midpoint of the olecranon process. By using the same reference line as that used for cadaveric dissection, the safe injection zone away from the neurovascular bundle was identified in 6 healthy volunteers via ultrasonography. We identified the neurovascular bundle and its location with respect to the distal end of the humerus and measured its depth from the skin surface.RESULTS: The MoEPs for the long, lateral, and medial heads were located at a median of 43.8%, 54.8%, and 60.4% of the length of the reference line in cadaver dissection. The safe injection zone of the medial head MoEPs corresponded to a depth of approximately 3.5 cm from the skin surface and 1.4 cm away from the humerus, as determined by sonography.CONCLUSION: Correct identification of the motor points for each head of the triceps brachii would increase the precision and efficacy of motor point injections to manage elbow extensor spasticity.
Acromion ; Botulinum Toxins ; Cadaver ; Elbow ; Head ; Healthy Volunteers ; Humerus ; Korea ; Motor Endplate ; Muscle Spasticity ; Muscles ; Needles ; Olecranon Process ; Schools, Medical ; Seoul ; Skin ; Ultrasonography ; Upper Extremity

A previous study has indicated that Krüppel-like factor 7 (KLF7), a transcription factor that stimulates Schwann cell (SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of microRNA-146b (miR-146b) affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with miRNA lentivirus, miRNA inhibitor lentivirus, or KLF7 siRNA lentivirus in vitro. The expression of miR146b and KLF7, as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft (ANA) followed by injection of GFP control vector or a lentiviral vector encoding an miR-146b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. miR-146b directly targeted KLF7 by binding to the 3'-UTR, suppressing KLF7. Up-regulation of miR-146b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing miR-146b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which miR-146b was expressed in vivo. Similarly, 4 weeks after the ANA, anti-miR-146b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0 (anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by miR-146b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.
Animals ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Disease Models, Animal ; Female ; Ganglia, Spinal ; cytology ; Gene Expression Regulation ; genetics ; physiology ; HEK293 Cells ; Humans ; Kruppel-Like Transcription Factors ; genetics ; metabolism ; Male ; MicroRNAs ; genetics ; metabolism ; Motor Endplate ; genetics ; Myelin P0 Protein ; metabolism ; Nerve Regeneration ; genetics ; physiology ; Nerve Tissue Proteins ; metabolism ; RNA, Small Interfering ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sciatic Neuropathy ; metabolism ; surgery ; therapy

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.
Animals ; Mice ; Mice, Knockout ; Motor Endplate ; Muscle, Skeletal* ; Muscles ; Myelin Sheath ; Neuregulin-1 ; Neuromuscular Junction ; Peripheral Nerves ; Presynaptic Terminals ; Protein-Tyrosine Kinases ; Schwann Cells* ; Synapses* ; Vertebrates

Since Willis described 'fatigable weakness' in 1672, most physicians consider it as a kind of hysteria due to the inconsistent fluctuation of symptoms. Erb presented three cases of 'bulbal palsy' in the 1870s, and Oppenheim and Hopper considered myasthenia gravis as a disease similar to curare poisoning and as a disease induced by attack of the motor centers by intrinsic toxins, respectively. In 1903, Elliot suggested that a 'chemical substance' mediates the nerve impulses at synapse. However, it was not until 1921 that this was demonstrated by Loewi, who provided evidence from the famous two-frog-hearts experiment. Dale later revealed the substance to be acetylcholine, and he also suggested that myasthenia gravis is due to a problem with the motor end plate. In 1934, Walker was prompted by the resemblance between myasthenia gravis and curare poisoning to apply physostigmine, a curare-poisoning antidote, to a patient, which produced a dramatic result. Since then the use of anticholinesterase inhibitors has been adopted for standard therapeutic modality. Some prominent surgeons have also applied thymectomy as a surgical modality. The most recent focus of myasthenia gravis has been immunological. In 1960, Simpson proposed the autoimmune hypothesis, and Chang et al. showed that snake venom contained a selective antagonist of the nicotinic acetylcholine receptor, alpha-bungarotoxin. The immunization of rabbits with acetylcholine receptor purified from the electrical organs of electric eels by Patrick et al. induced myasthenic symptoms and signs, and these were reversed by acetylcholinesterase inhibitors. The role of the autoimmune system has led to the introduction of an immunosuppressive modality and plasma exchange to the field of clinical neurology.
Acetylcholine ; Action Potentials ; Bungarotoxins ; Cholinesterase Inhibitors ; Curare ; Electrophorus ; History of Medicine ; Humans ; Hysteria ; Immunization ; Motor Endplate ; Myasthenia Gravis ; Physostigmine ; Plasma Exchange ; Rabbits ; Receptors, Nicotinic ; Snake Venoms ; Synapses ; Thymectomy

OBJECTIVE: To report an unsuspected adaptive plasticity of single upper motor neurons and of primary motor cortex found after microsurgical connection of the spinal cord with peripheral nerve via grafts in paraplegics and focussed discussion of the reviewed literature. METHODS: The research aimed at making paraplegics walk again, after 20 years of experimental surgery in animals. Amongst other things, animal experiments demonstrated the alteration of the motor endplates receptors from cholinergic to glutamatergic induced by connection with upper motor neurons. The same paradigm was successfully performed in paraplegic humans. The nerve grafts were put into the ventral-lateral spinal tract randomly, without possibility of choosing the axons coming from different areas of the motor cortex. RESULTS: The patient became able to selectively activate the re-innervated muscles she wanted without concurrent activities of other muscles connected with the same cortical areas. CONCLUSION: Authors believe that unlike in nerve or tendon transfers, where the whole cortical area corresponding to the transfer changes its function a phenomenon that we call "brain plasticity by areas", in our paradigm due to the direct connection of upper motor neurons with different peripheral nerves and muscles via nerve grafts motor learning occurs based on adaptive neuronal plasticity so that simultaneous contractions of other muscles are prevented. We propose to call it adaptive functional "plasticity by single neurons". We speculate that this phenomenon is due to the simultaneous activation of neurons spread in different cortical areas for a given specific movement, whilst the other neurons of the same areas connected with peripheral nerves of different muscles are not activated at the same time. Why different neurons of the same area fire at different times according to different voluntary demands remains to be discovered. We are committed to solve this enigma hereafter.
Animal Experimentation ; Animals ; Axons ; Compensation and Redress ; Contracts ; Fires ; Humans ; Learning ; Motor Cortex ; Motor Endplate ; Motor Neurons ; Muscles ; Neuronal Plasticity ; Neurons ; Paraplegia ; Peripheral Nerves ; Plastics ; Pyramidal Tracts ; Spinal Cord ; Tendon Transfer ; Transplants

OBJECTIVETo investigate the compensative mechanism of no further impairment of the upper limb after ipsilateral C(7) transfer for treatment of root avulsion of C(5)-C(6) of the brachial plexus.

METHODSSixty Sprague Dawley (SD) rats were randomly divided into a C7-transection group and a control group, 30 rats each. In the C(7)-transection group, the left forelimbs of the animals underwent transection of ipsilateral C(7) nerve root while C(5) and C(6) nerve roots were avulsed. In the control group, the left forelimbs only underwent C(5) and C(6) root avulsion. The representative muscles of C(7) (innervated mainly by C(7)) including latissimus dorsi, triceps, extensor carpi radialis brevis and extensor digitorum communis were evaluated with neurophysiological investigation, muscular histology and motor end plate histomorphometry 3, 6 and 12 weeks after operation. The right forelimbs of all rats were taken as the control sides.

RESULTSThree weeks after operation, the recovery rates of amplitudes of compound muscle action potential (CMAP) and CMAP latency, muscular wet weight and cross-sectional area of muscle fibers, and area of postsynaptic membranes of those four representative muscles in the C(7)-transection group were significantly lower than those of the control group (P less than 0.05 or P less than 0.01). Six weeks postoperatively, the recovery rates of CMAP amplitude and latency of the triceps showed no significant difference between the C(7)-transection group and the control group (P larger than 0.05). For the extensor carpi radialis brevis and the extensor digitorum communis, the recovery rates of the cross-sectional area of muscle fibers, the amplitude and latency of CMAP and the area of postsynaptic membranes showed no significant difference between the two groups (P larger than 0.05), while the rest parameters were still significantly different between the two group (P less than 0.05 or P less than 0.01). As far as the ultramicrostructure was concerned in the C(7)-transection group, more motor end plates of four representative muscles were observed and their ultramicrostructure also had a tendency to mature as compared with those of 3 weeks postoperatively. Twelve weeks after operation, all parameters of the C(7)-transection group were not significantly different from those of the control group (P >0.05). In the C7-transection group, the motor end plates were densely distributed and their ultramicrostructure in four representative muscles appeared to be mature as compared with those of the control group.

CONCLUSIONSAfter ipsilateral C(7) transfer for treatment of root avulsion of C(5)-C(6) of the brachial plexus, the nerve fibers of the lower trunk can compensatively innervate fibers of C(7)-representative muscles by means of motor end plate regeneration, so there is no further impairment on the injured upper limb.

Animals ; Brachial Plexus ; injuries ; surgery ; Motor Endplate ; ultrastructure ; Nerve Transfer ; methods ; Rats ; Rats, Sprague-Dawley ; Spinal Nerve Roots ; injuries ; Upper Extremity ; physiology

OBJECTIVETo study the histochemical changes of muscle fibers and motor end-plates of paravertebral muscles, and analyze their relationship with the etiology of scoliosis associated with syringomyelia as compared with adolescent idiopathic scoliosis (AIS) and non-scoliotic patients.

METHODSAll the enrolled patients were divided into three groups: Group I consisted of 20 patients with scoliosis associated with syringomyelia, Group II included 16 patients with AIS, and Group III included 10 patients without scoliosis. Bilateral biopsy of paravertebral muscles was performed during scheduled spinal surgery. HE staining, nicotin-lateral biopsy of paravertebral muscles was performed during scheduled spinal surgery. HE staining, nicotinamide adenine dinucleotide hydrogen-tetrazolium reductase ( NADH-TR), and alpha-naphthyl acetate esterase staining techniques were used for histological evaluation. Neurogenic and myogenic pathological changes and changes of motor end-plates of paravertebral muscles were compared among these three groups.

RESULTSNeurogenic pathological changes of muscle fibers were found in 12 (60% ) patients in Group I but was not found in Group II and III. The numbers of both T0 type motor end-plates and pathological end-plates on the convex side were significantly larger than those on the concave side in Group I ( P < O. 05 ). In Group II , however, the numbers of both T0 type motor end-plates and pathological end-plates on the concave side were significantly larger than those on the convex side (P < 0.05). No significant difference was found between two sides in Group III.

CONCLUSIONThe histochemical changes of paravertebral muscles in patients with scoliosis and syringomyelia are different from those in AIS patients. It is suggested that a primary denervation of paravertebral muscles exist in scoliosis associated with syringomyelia, which may play a role in the pathogenesis of scoliosis.

Adolescent ; Adult ; Case-Control Studies ; Child ; Female ; Humans ; Male ; Motor Endplate ; pathology ; Muscle Fibers, Skeletal ; pathology ; Muscle, Skeletal ; pathology ; Scoliosis ; complications ; pathology ; Staining and Labeling ; Syringomyelia ; complications ; pathology

OBJECTIVETo explore measures to prevent motor endplate degeneration and muscular atrophy after motor nerve injury.

METHODSThirty Sprague-Dawley rats were randomized into 3 equal groups. In two of the groups, the right common peroneal nerves of the rats were transected and immediately sutured with implantation of collagen gel carrier of acidic fibroblast growth factor (aFGF) or the empty carrier into the denervated tibialis anterior muscles. In the control group, the transected nerves were sutured without implantation. Six weeks after the operation, morphological and electrophysiological examinations were performed.

RESULTSIn the control rats and those with empty collagen gel carrier implantation, obvious motor endplate degeneration and muscular atrophy occurred, which were not obvious in rats receiving aFGF carrier implantation. The decrement of repetitive nerve stimulation was significantly greater in the former two groups than in the latter.

CONCLUSIONImplantation of collagen gel carrier of aFGF may prevent motor endplate degeneration and facilitate functional recovery of the neuromuscular junction after motor nerve injury.

Animals ; Electrophysiology ; Female ; Fibroblast Growth Factor 1 ; pharmacology ; therapeutic use ; Male ; Motor Endplate ; drug effects ; injuries ; physiopathology ; Muscle Denervation ; methods ; Muscular Atrophy ; pathology ; physiopathology ; prevention & control ; Nerve Degeneration ; physiopathology ; prevention & control ; Nerve Regeneration ; drug effects ; Peroneal Nerve ; drug effects ; injuries ; physiopathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the changes of acetylcholine receptor (AChR) distribution at the neuromuscular junction (i.e. motor end-plate) following the free neurovascular muscle transfer.

METHODSAChR in the gracilis muscle of the Wistar rat following free neurovascular transfer were labeled by fluorescent alpha-bungarotoxin and radioiodinated alpha-bungarotoxin. Then confocal microscope and gamma-counting were estimated to ACHR, qualitatively and quantitatively.

RESULTSThe junctional AChR numbers decreased to a minimum at the fourth week postoperatively, whereas the extrajunctional receptor numbers increased. From the fifth week postoperatively, the number of junctional AChR's increased. Even at 30 weeks after transfer, the morphology of the neuromuscular junction failed to return to the preoperative style. The number of acetylcholine receptors at the reinnervated neuromuscular junction also remained lower than the control.

CONCLUSIONThe persistent weakness following free neurovascular muscle transfer may be attributed to these qualitative and quantitative changes at the neuromuscular junction.

Animals ; Female ; Motor Endplate ; metabolism ; Muscle, Skeletal ; transplantation ; Nerve Regeneration ; Postoperative Period ; Rats ; Rats, Wistar ; Receptors, Cholinergic ; metabolism

To study the effects of ciliary neurotrophic factor (CNTF) on denervated skeletal muscle atrophy and to find a new approach to ameliorate atrophy of denervated muscle, a model was established by cutting the right sciatic nerve in 36 Wistar mice, with the left side serving as control. Then they were divided into two groups randomly. CNTF (1 U/ml) 0.1 ml was injected into the right tibial muscle every day in experimental group, and saline was used into another group for comparison. The muscle wet weight, muscle total protein, Ca2+, physiological response and morphology were analyzed on the 7th, 14th and 28th day after operation. Our results showed that compared to control group, there was a significant increase in muscle wet weight, total protein, Ca2+, muscle fiber cross-section area in CNTF group (P < 0.05). CNTF could ameliorate the decrease of tetanic tension (PO), post-tetanic twitch potentiation (PTP), and the prolonged muscle relaxation time (RT) caused by denervation (P < 0.05). The motor end-plate areas 7 days and 14 days after denervation was similar (P > 0.05), but significantly larger 28 days after the denervation (P < 0.05). Our results suggest that CNTF exerts myotrophic effects by attenuating the morphological and functional changes associated with denervation of rat muscles and has protective effects on denervated muscle and motor end plate.
Animals ; Ciliary Neurotrophic Factor ; pharmacology ; Male ; Motor Endplate ; pathology ; physiopathology ; Muscle Denervation ; adverse effects ; Muscle, Skeletal ; innervation ; pathology ; physiopathology ; Muscular Atrophy ; etiology ; prevention & control ; Random Allocation ; Rats ; Rats, Wistar ; Sciatic Nerve ; surgery