Majority Of Endplates Research Articles

Motor unit recovery following Smn restoration in mouse models of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a childhood motor neuron disease caused by anomalies in the SMN1 gene. Although therapeutics have been approved for the treatment of SMA, there is a therapeutic time window, after which efficacy is reduced. Hallmarks of motor unit pathology in SMA include loss of motor-neurons and neuromuscular junction (NMJs). Following an increase in Smn levels, it is unclear how much damage can be repaired and the degree to which normal connections are re-established. Here, we perform a detailed analysis of motor unit pathology before and after restoration of Smn levels. Using a Smn-inducible mouse model of SMA, we show that genetic restoration of Smn results in a dramatic reduction in NMJ pathology, with restoration of innervation patterns, preservation of axon and endplate number and normalized expression of P53-associated transcripts. Notably, presynaptic swelling and elevated Pmaip levels remained. We analysed the effect of either early or delayed treated of an antisense oligonucleotide (ASO) targeting SMN2 on a range of differentially vulnerable muscles. Following ASO administration, the majority of endplates appeared fully occupied. However, there was an underlying loss of axons and endplates, which was more prevalent following a delay in treatment. There was an increase in average motor unit size following both early and delayed treatment. Together this work demonstrates the remarkably regenerative capacity of the motor neuron following Smn restoration, but highlights that recovery is incomplete. This work suggests that there is an opportunity to enhance neuromuscular junction recovery following administration of Smn-enhancing therapeutics.

Nerve growth factor and basic fibroblast growth factor promote reinnervation by nerve-muscle-endplate grafting.

This study was designed to test whether exogenous application of nerve growth factor (NGF) and basic fibroblast growth factor (FGF-2) to muscles reinnervated with nerve-muscle-endplate band grafting (NMEG) could promote specific outcomes. The right sternomastoid muscle in adult rats was experimentally denervated and immediately reinnervated by implanting an NMEG pedicle from the ipsilateral sternohyoid muscle. A fibrin sealant containing NGF and FGF-2 was focally applied to the implantation site. Maximal tetanic force, muscle weight, regenerated axons, and motor endplates were analyzed 3 months after treatment. Mean tetanic force, wet muscle weight, and number of regenerated axons in the treated muscles were 91%, 92%, and 84% of the contralateral controls, respectively. The majority of endplates (86%) in the treated muscles were reinnervated by regenerated axons. Focal administration of NGF and FGF-2 promotes efficacy of the NMEG technique. Muscle Nerve 57: 449-459, 2018.

Innervation of pathologies in the lumbar vertebral end plate and intervertebral disc

Background contextMagnetic resonance imaging (MRI) has limited diagnostic value for chronic low back pain because of the unclear relationship between any anatomic abnormalities on MRI and pain reported by the patient. Assessing the innervation of end plate and disc pathologies—and determining the relationship between these pathologies and any abnormalities seen on MRI—could clarify the sources of back pain and help identify abnormalities with enhanced diagnostic value. PurposeTo quantify innervation in the vertebral end plate and intervertebral disc and to relate variation in innervation to the presence of pathologic features observed by histology and conventional MRI. Study design/settingA cross-sectional histology and imaging study of vertebral end plates and intervertebral discs harvested from human cadaver spines. MethodsWe collected 92 end plates and 46 intervertebral discs from seven cadaver spines (ages 51–67 years). Before dissection, the spines were scanned with MRI to grade for Modic changes and high-intensity zones (HIZ). Standard immunohistochemical techniques were used to localize the general nerve marker protein gene product 9.5. We quantified innervation in the following pathologies: fibrovascular end-plate marrow, fatty end-plate marrow, end-plate defects, and annular tears. ResultsNerves were present in the majority of end plates with fibrovascular marrow, fatty marrow, and defects. Nerve density was significantly higher in fibrovascular end-plate marrow than in normal end-plate marrow (p<.001). Of the end plates with fibrovascular and fatty marrow, less than 40% were Modic on MRI. Innervated marrow pathologies collocated with more than 75% of the end plate defects; hence, innervation was significantly higher in end plate defects than in normal end plates (p<.0001). In the disc, nerves were observed in only 35% of the annular tears; in particular, innervation in radial tears tended to be higher than in normal discs (p=.07). Of the discs with radial tears, less than 13% had HIZ on T2 MRI. Innervation was significantly less in radial tears than in fibrovascular end-plate marrow (p=.05) and end-plate defects (p=.02). ConclusionsThese findings indicate that vertebral end-plate pathologies are more innervated than intervertebral disc pathologies and that many innervated end-plate pathologies are not detectable on MRI. Taken together, these findings suggest that improved visualization of end-plate pathologies could enhance the diagnostic value of MRI for chronic low back pain.

Sagittal endplate morphology of the lower lumbar spine

The sagittal profile of lumbar endplates is discrepant from current simplified disc replacement and fusion device design. Endplate concavity is symmetrical in the coronal plane but shows considerable variability in the sagittal plane, which may lead to implant-endplate mismatch. The aim of this investigation is to provide further analysis of the sagittal endplate morphology of the mid to lower lumbar spine study (L3–S1), thereby identifying the presence of common endplate shape patterns across these levels and providing morphological reference values complementing the findings of previous studies. Observational study. A total of 174 magnetic resonance imaging (MRI) scans of the adult lumbar spine from the digital archive of our centre, which met the inclusion criteria, were studied. Superior (SEP) and inferior (IEP) endplate shape was divided into flat (no concavity), oblong (homogeneous concavity) and ex-centric (inhomogeneous concavity). The concavity depth (ECD) and location of concavity apex (ECA) relative to endplate diameter of the vertebrae L3–S1 were determined. Flat endplates were only predominant at the sacrum SEP (84.5%). The L5 SEP was flat in 24.7% and all other endplates in less than 10%. The majority of endplates were concave with a clear trend of endplate shape becoming more ex-centric from L3 IEP (56.9% oblong vs. 37.4% ex-centric) to L5 IEP (4% oblong vs. 94.3% ex-centric). Ex-centric ECA were always found in the posterior half of the lumbar endplates. Both the oblong and ex-centric ECD was 2-3 mm on average with the IEP of a motion segment regularly possessing the greater depth. A sex- or age-related difference could not be found. The majority of lumbar endplates are concave, while the majority of sacral endplates are flat. An oblong and an ex-centric endplate shape can be distinguished, whereby the latter is more common at the lower lumbar levels. The apex of the concavity of ex-centric discs is located in the posterior half of the endplate and the concavity of the inferior endplate is deeper than that of the superior endplate. Based on the above, the current TDR and ALIF implant design does not sufficiently match the morphology of lumbar endplates in the sagittal plane.

Single fiber EMG in a congenital myasthenic syndrome associated with facial malformations

Six patients with a newly described genetic syndrome in Iraqi and Iranian Jews of congenital myasthenia associated with facial malformations were studied with voluntary and stimulation single fiber EMG (SFEMG). Voluntary SFEMG revealed abnormal jitter in all patients in both extensor digitorum communis (EDC) and orbicularis oculi (OOC) muscles, though much smaller in the clinically unaffected EDC. SFEMG study of OOC muscle by axonal stimulation at rates from 1 to 48 Hz showed the most increased jitter at the highest stimulation frequencies in the majority of end-plates, one-third of which showed maximal jitter at intermediate rates. These results may suggest a postsynaptic abnormality as the underlying cause for the neuromuscular transmission defect, and demonstrate the usefulness of SFEMG in the diagnosis of congenital myasthenia.

The Elimination of Polyneuronal Innervation of End-Plates in Developing Rat Muscles with Altered Function

Publisher Summary This chapter discusses the elimination of polyneuronal innervation from developing end-plates in rat extensor digitorum longus (EDL) muscles with altered function: (1) during compensatory hypertrophy and (2) after de-afferentation. Results show that the EDL muscles became overloaded, and underwent compensatory hypertrophy after removal of the tibialis anterior muscles in new-born rats. The maturation of end-plates was speeded up. Electrophysiological examination revealed that 74% end-plates already had a monoaxonal supply by day 9, and 94% were monoaxonally supplied by day 14, as compared with 43% and 82% monoaxonal end-plates in corresponding control muscles. After bilateral section of lumbosacral dorsal roots and high transection of the spinal cord in l day old rats, active movements were restricted and the maturation of end-plates in EDL muscles was retarded; only 24% and 37% end plates became monoaxonal by day 9 as determined by electrophysiological and histological method respectively. No difference was found between deafferented and control muscles by day 14, when about 80% of all end-plates investigated already had a monoaxonal supply. The maturation of motor end-plates thus appears to be speeded up by compensatory hypertrophy and slowed down by de-afferentation. The retardation observed after de-afferentation is only temporary; the majority of end-plates become monoaxonally supplied in two weeks time in both experimental and control muscles.