Spinal Anterior Horn Cells Research Articles

Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice.

Stroke can cause Wallerian degeneration in regions outside of the brain, particularly in the corticospinal tract. To investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke, we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal tract. We first used a routine, sensitive marker of axonal injury, amyloid precursor protein, to examine Wallerian degeneration of the corticospinal tract. An antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex, with no positive signal in distal parts of the corticospinal tract, at all time points. To improve visualization of Wallerian degeneration, we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing axons. Using this approach, we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after stroke. In addition, microglia mobilized and activated early, from day 7 after stroke, but did not maintain a phagocytic state over time. Meanwhile, astrocytes showed relatively delayed mobilization and a moderate response to Wallerian degeneration. Moreover, no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal tract. In conclusion, our data provide evidence for dynamic, pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

A new waveform analysis method reflecting the diversity of F-wave Waveforms–Waveform types in healthy subjects based on the combined use of the additive averaging method and histograms-

BackgroundF-waves, which are an indicator of the excitability of spinal cord anterior horn cells, are characterized by diverse waveforms. However, no analytical method has yet been development that fully reflects the diversity of such waveforms. The present study examined whether or not the change in the amplitude by the additive averaging process reflects the dispersion of the peak. New methodThe average amplitude of each waveform and the decrease in the amplitude after the additive averaging process were determined. The correlation between the decrease in the amplitude and the density of the peak was then examined. The histogram was also used to classify the type of waveform dispersion based on the characteristics of the peak latency. ResultsNo correlation was found between the change in the amplitude and the peak density. However, the F-waves obtained from the ulnar nerve of healthy subjects were able to be classified into five types. Comparison with existing methodThe parameters of an F-wave analysis are the rise latency, the amplitude and the persistence, and many reports have examined F-waves based on the changes in these values. The present study explored new parameters focusing on the waveform of F-waves reflecting the motor unit. ConclusionThe results of this study may help to establish a standard of comparison when using the F wave to evaluate spasticity due to upper motor neuron disorders.

Effects of Clenching Strength on Exercise Performance: Verification Using Spinal Function Assessments.

This study aimed to determine the relationship between exercise performance and spinal function based on clenching strength. Low-intensity clenching contributes to joint movement, whereas high-intensity clenching contributes to joint fixation. Randomized crossover trial. Level 3. Two experiments were conducted using 2 groups of 20 healthy adults. The 4 clenching conditions in experiment 1 were 0%, 12.5%, 25%, and 50% of the maximum voluntary contraction (MVC) of the masseter muscle. Experiment 2 consisted of 3 conditions: no-bite condition, moderate effort, and maximum effort (max condition). In experiment 1, spinal function and ankle dorsiflexion tasks were measured for each clenching condition, and the ankle dorsiflexion task was measured in experiment 2. Regarding spinal function, we measured spinal reciprocal inhibition (RI) and excitability of spinal anterior horn cells. For the ankle dorsiflexion task, ankle dorsiflexion MVC was performed for 3 seconds under each clenching condition. The items analyzed were reaction time, peak ankle dorsiflexion torque, and soleus (Sol)/tibialis anterior (TA) electromyography (EMG) ratio. The results of experiment 1 illustrated that RI was significantly attenuated or eliminated with increasing clenching strength (>25% MVC). Spinal anterior horn cell excitability increased significantly with increasing clenching strength. The peak torque was significantly higher at 50% MVC than that at 0% MVC. In experiment 2, the peak torque was significantly higher under moderate and max conditions than no-bite condition, and the Sol/TA EMG ratio was significantly higher under max condition than that under moderate condition. The results illustrated that during high-strength clenching (≥50% MVC), antagonist muscles are activated simultaneously to increase muscle strength. High-strength clenching improved kinetic performance (joint fixation), whereas low-strength clenching (<50% MVC) enhanced exercise performance (joint movement).

Benign monomelic amyotrophy of lower limb in a cohort of chinese patients.

BackgroundBenign monomelic amyotrophy of lower limb (BMALL) is a neurogenic syndrome representing an unclear field. Further studies might be helpful to elucidate uncertainties regarding causation, outcome, and the risk of progression to amyotrophic lateral sclerosis (ALS).MethodsAccording to the inclusion and exclusion criteria, 37 patients with BMALL were retrospectively collected in three neuromuscular centers from January 2012 to October 2018. The detailed medical data were summarized. Multiple laboratory tests were examined. Routine electrophysiological examinations, muscle MRI of lower limbs, and muscle biopsy were conducted.ResultsThe cohort included 24 male and 13 female cases with median age of onset 47 years. Muscle MRI revealed that the distribution of involved muscles matched with the extent of fat infiltration, so the pattern muscle atrophy can be divided into the following four types: six patients with thigh atrophy (type I), 14 patients with leg atrophy (type II); 10 patients with disproportionate atrophy in both thigh and leg (type III); and seven patients with well‐proportionate atrophy in both thigh and leg (type IV). Electrophysiological findings showed neurogenic pattern, spontaneous activity, and abnormal H reflex, which suggested a disorder of spinal anterior horn cell in the patients with types I‐III. However, no electrophysiological abnormalities were found in the patients with type IV. Muscle pathology varied from almost normal pattern to advanced neurogenic pattern in nine biopsied patients. Follow‐up showed that two patients with type II developed to ALS four years later, and all patients with type IV were in stable condition without any complaints.ConclusionMuscle MRI was useful to exactly localize the distribution of involved muscles in BMALL patients. The distribution of atrophic muscles can be roughly divided into four types based on the MRI features. The classification of distributing types might be as an indicator for the prognosis of BMALL.

The Dying Forward Hypothesis of ALS: Tracing Its History

The site of origin of amyotrophic lateral sclerosis (ALS), although unsettled, is increasingly recognized as being cortico-fugal, which is a dying-forward process primarily starting in the corticomotoneuronal system. A variety of iterations of this concept date back to over 150 years. Recently, the hallmark TAR DNA-binding protein 43 (TDP-43) pathology, seen in >95% of patients with ALS, has been shown to be largely restricted to corticofugal projecting neurons (“dying forward”). Possibly, soluble but toxic cytoplasmic TDP-43 could enter the axoplasm of Betz cells, subsequently causing dysregulation of nuclear protein in the lower brainstem and spinal cord anterior horn cells. As the disease progresses, cortical involvement in ALS becomes widespread, including or starting with frontotemporal dementia, implying a broader view of ALS as a brain disease. The onset at the motor and premotor cortices should be considered a nidus at the edge of multiple cortical networks which eventually become disrupted, causing failure of a widespread cortical connectome.

Tetanic stimulation of the peripheral nerve augments motor evoked potentials by re-exciting spinal anterior horn cells.

Tetanic stimulation of the peripheral nerve, immediately prior to conducting transcranial electrical stimulation motor evoked potential (TES-MEP), increases MEP amplitudes in both innervated and uninnervated muscles by the stimulated peripheral nerve; this is known as the remote augmentation of MEPs. Nevertheless, the mechanisms underlying the remote augmentation of MEPs remain unclear. Although one hypothesis was that remote augmentation of MEPs results from increased motoneuronal excitability at the spinal cord level, the effect of spinal anterior horn cells has not yet been investigated. We aimed to investigate the effect of tetanic stimulation of the peripheral nerve on spinal cord anterior horn cells by analyzing the F-wave. We included 34 patients who underwent elective spinal surgeries and compared the changes in F-waves and TES-MEPs pre- and post-tetanic stimulation of the median nerve. F-wave analyses were recorded by stimulating the median and tibial nerves. TES-MEPs and F-wave analyses were compared between baseline and post-tetanic stimulation time periods using Wilcoxon signed-rank tests. A significant augmentation of MEPs, independent of the level corresponding to the median nerve, was demonstrated. Furthermore, F-wave persistence was significantly increased not only in the median nerve but also in the tibial nerve after tetanic stimulation of the median nerve. The increased F-wave persistence indicates an increase of re-excited motor units in spinal anterior horn cells. These results confirm the hypothesis that tetanic stimulation of the peripheral nerve may cause remote augmentation of MEPs, primarily by increasing the excitability of the anterior horn cells.

Effect of different pressure stimulation of muscle on the excitability of the spinal anterior horn cells

Effect of different pressure stimulation of muscle on the excitability of the spinal anterior horn cells

Changes in the excitability of the spinal anterior horn cells of the abductor digiti minimi muscle during hand mental rotation tasks: a study of viewpoints

Changes in the excitability of the spinal anterior horn cells of the abductor digiti minimi muscle during hand mental rotation tasks: a study of viewpoints

Ultrastructure of spinal anterior horn cells in human Niemann‐Pick type C (NPC) patient and mouse model of NPC with retroposon insertion in NPC1 genes

Niemann-Pick disease type C (NPC) is a neurovisceral lipid-storage disease. Although NPC patients show lipid storage in anterior horn cells of the spinal cord, little information is available regarding the electron microscopic analyses of the morphologies of intra-endosomal lipid like-materials in the anterior horn cells of NPC patients. In this study, we elucidated the intra-endosomal ultrastructures in spinal anterior horn cells in an NPC patient, as well as in mutant BALB/c NPC1-/- mice with a retroposon insertion in the NPC1 gene. These morphologies were classified into four types: vesicle, multiple concentric sphere (MCS), membrane, and rose flower. The percentages of the composition in the NPC patient and NPC1-/- mice were: vesicle (55.5% and 14.9%), MCS (15.7% and 3.4%), membrane (23.6% and 57.1%), and rose flower (5.2% and 24.6%), respectively. Formation of the intra-endosomal structures could proceed as follows: (i) a vesicle or MCS buds off the endosome into the lumen; (ii) when a vesicle breaks down, a membrane is formed; and (iii) after an MCS breaks down, a rose flower structure is formed. Our new finding in this study is that ultrastructural morphology is the same between the NPC patient and NPC1-/- mice, although there are differences in the composition.

Circulating MicroRNAs as Diagnostic Biomarkers for Motor Neuron Disease.

Motor neuron disease (MND) is a kind of neurodegenerative disease that selectively invades spinal cord anterior horn cells, brainstem motor neurons, cortical pyramidal cells and the pyramidal tract. The main clinical features are the symptoms and signs of impaired upper and lower motor neurons, manifested as muscle weakness, atrophy and pyramidal tract signs. Histopathology has shown the disappearance of pyramidal cells in the motor cortex, loss of motor neurons in the anterior horn of the spinal cord and brainstem, and degeneration of the corticospinal tract. Due to the lack of effective treatment methods, the prognosis is generally poor, so it is of great significance to confirm the diagnosis early by various means. However, the current diagnosis of MND mainly relies on the combination of clinical manifestations and neurophysiological examinations, lacking effective means of early diagnosis. Circulating microRNA (CmiRNA) is a kind of stable miRNA molecule in serum, plasma and other body fluids, which has the characteristics of distinct differential expression, sensitive detection and convenient sample collection. As a possible new biomarker of MND, CmiRNA can not only reveal the pathophysiological process of MND, but also monitor disease progression and response to drug therapy. With the development of miRNA detection technology, more and more CmiRNAs as biomarkers with potential diagnostic value have been investigated. In this review, we explored the possibility of circulating samples as different sources of biomarkers for the diagnosis of MND, analyzing the progress of CmiRNA detection techniques, and presenting potential diagnostic MND biomarkers that have been reported.

Clinical diagnosis and surgical treatment of cervical spondylosis with distal upper extremity amyotrophy

Objective To summarize the clinical features of cervical spondylosis with distal upper extremity amyotrophy; and further analyze the clinical efficacy of cervical anterior decompression and fusion on cervical spondylosis with distal upper extremity amyotrophy. Methods Thirty cases of cervical spondylosis with distal upper extremity amyotrophy were analyzed retrospectively from June 2006 to June 2015. nineteen males and eleven females with an average age of 55.20±9.08 years (41 to 72 years) were included. The preoperative course was 1 to 108 months with a median of 6 months. The muscle extent of the affected group, the segmentation and location of spinal canal stenosis, and the results of neurophysiological examination were analyzed. The muscular strength recovery of atrophic muscles was evaluated by Manual Muscle Testing (MMT), and the clinical satisfaction was assessed at the last followed up. Results The muscles involved in patients of cervical spondylosis with distal upper extremity amyotrophy are mainly the thenar muscle (17 cases, 56.7%), interosseous muscle (15 cases, 50.0%), and shypothenar muscles (13 cases, 43.3%). Most cases of imaging findings showed multi-segmental degeneration, of which C5, 6 (24 cases, 80.0%), C6,7 (21 cases, 70.0%) segments were most common, and the types of anterior compression: 23 segments (33.5%) of the central type, 37 segments (54.4%) of the lateral-central type, and 8 segments (11.8%) of the foramen type. Neuroelectrophysiological examination showed that cervical spinal cord anterior horn cells or nerve root damage, the most commonly involved segments of C7, C8, T1(18 cases, 60.0%). The average follow-up time was 36.8 months. At the last follow-up, MMT assessment showed that thirteen patients (43.3%) in this group had muscle strength recovery for more than one grade at the last follow-up. The average clinical satisfaction was 73.4%. Conclusion The clinical diagnosis of cervical spondylosis with distal upper extremity amyotrophy requires a combination of clinical symptoms, imaging findings and neurophysiological examination results for comprehensive judgment. Cervical anterior decompression and fusion can effectively prevent the progression of cervical spondylosis in distal upper extremity amyotrophy patients, and some patients can get a good muscle recovery. Key words: Cervical vertebrae; Spinal cord compression; Muscular atrophy; Spinal fusion

P1-16-03. The influence of motor imagery and practice time on the accuracy and excitability of spinal anterior horn cells

P1-16-03. The influence of motor imagery and practice time on the accuracy and excitability of spinal anterior horn cells

Reinnervation of spinal cord anterior horn cells after median nerve repair using transposition with other nerves.

Our previous studies have confirmed that during nerve transposition repair to injured peripheral nerves, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively repair distal nerve and target muscle tissue and restore muscle motor function. To observe the effect of nerve regeneration and motor function recovery after several types of nerve transposition for median nerve defect (2 mm), 30 Sprague-Dawley rats were randomly divided into sham operation group, epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group. Three months after nerve repair, the wrist flexion test was used to evaluate the recovery of wrist flexion after regeneration of median nerve in the affected limbs of rats. The number of myelinated nerve fibers, the thickness of myelin sheath, the diameter of axons and the cross-sectional area of axons in the proximal and distal segments of the repaired nerves were measured by osmic acid staining. The ratio of newly produced distal myelinated nerve fibers to the number of proximal myelinated nerve fibers was calculated. Wet weights of the flexor digitorum superficialis muscles were measured. Muscle fiber morphology was detected using hematoxylin-eosin staining. The cross-sectional area of muscle fibers was calculated to assess the recovery of muscles. Results showed that wrist flexion function was restored, and the nerve grew into the distal effector in all three nerve transposition groups and the epineurial neurorrhaphy group. There were differences in the number of myelinated nerve fibers in each group. The magnification of proximal to distal nerves was 1.80, 3.00, 2.50, and 3.12 in epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group, respectively. Nevertheless, axon diameters of new nerve fibers, cross-sectional areas of axons, thicknesses of myelin sheath, wet weights of flexor digitorum superficialis muscle and cross-sectional areas of muscle fibers of all three groups of donor nerves from different anterior horn motor neurons after nerve transposition were similar to those in the epineurial neurorrhaphy group. Our findings indicate that donor nerve translocation from different anterior horn motor neurons can effectively repair the target organs innervated by the median nerve. The corresponding spinal anterior horn motor neurons obtain functional reinnervation and achieve some degree of motor function in the affected limbs.

Influence of Expiration and Inspiration during Motor Imagery on the Excitability of the Spinal Anterior Horn Cell

Influence of Expiration and Inspiration during Motor Imagery on the Excitability of the Spinal Anterior Horn Cell

The influence of motor imagery and practice time on the accuracy and excitability of spinal anterior horn cells

The influence of motor imagery and practice time on the accuracy and excitability of spinal anterior horn cells

Effects of motor imagery on accuracy, expeditiously and excitability of spinal anterior horn cell

Effects of motor imagery on accuracy, expeditiously and excitability of spinal anterior horn cell

Downregulation of Neuronal and Dendritic Connexin36-Made Electrical Synapses Without Glutamatergic Axon Terminals in Spinal Anterior Horn Cells From the Early Stage of Amyotrophic Lateral Sclerosis.

Connexin36 (Cx36) forms gap junctions between neurons, which are called electrical synapses, enabling adjacent neurons to communicate directly. The participation of chemical synapses in neurodegeneration in amyotrophic lateral sclerosis (ALS) has long been indicated, but it remains unclear whether electrical synapses are involved in the pathogenesis of ALS. We performed extensive immunopathological analyses using mutant superoxide dismutase 1 (SOD1G93A) transgenic mice and their littermates to investigate whether Cx36-made electrical synapses are affected in motor neuron diseases. We found that in the lamina IX of the lumbar spinal cord from wild type mice, about half of the Cx36 puncta existed independently of chemical synapse markers, while the rest coexisted with chemical synapse markers, such as vesicular glutamate transporter 1 (VGLUT1), which is a glutamatergic axon terminal marker, and/or glutamate decarboxylase 65 (GAD65), which is a GABAergic axon terminal marker. Cx36 single or Cx36/GAD65 double positive puncta, but not VGLUT1-containing puncta, were preferentially decreased on neuronal and dendritic surfaces of the anterior horn cells in the early stage of SOD1G93A ALS mice. Moreover, in five human autopsied sporadic ALS cases with bulbar or upper limb onset, Cx36 immunoreactivity was diminished in the proximal dendrites and neuropils of well-preserved large motor neurons in the lumbar anterior horns. These findings suggest that downregulation of neuronal and dendritic Cx36 in the spinal anterior horns commonly occurs from the early stage of hereditary and sporadic ALS. Cx36-made electrical synapses without glutamatergic signaling appear to be more vulnerable than other chemical synapses and electrical synapses with glutamatergic signaling in the early stage of motor neuron degeneration, suggesting involvement of Cx36-made electrical synapses in the pathogenesis of human ALS.

Does the duration of motor imagery affect the excitability of spinal anterior horn cells?

Purpose: Motor imagery, the process of imagining a physical action, has been shown to facilitate the excitability of spinal anterior horn cells. In the acute phase after a stroke, the excitability of spinal anterior horn cells is significantly reduced, which leads to motor deficits. This loss of movement can be prevented by increasing the excitability of spinal anterior horn cells immediately following an injury. Motor imagery is an effective method for facilitating the excitability of spinal anterior horn cells in patients with impaired movement; however, the optimal duration for motor imagery is unclear.Materials and Methods: To investigate time-dependent changes in spinal anterior horn cell excitability during motor imagery, healthy adult participants were recruited to measure the F-wave, an indicator of anterior horn cell excitability. F-waves were measured from participants at baseline, during motor imagery, and post-motor imagery. During motor imagery, participants imagined isometric thenar muscle activity at 50% maximum voluntary contraction for 5 min. F-waves were measured at 1, 3, and 5 min after beginning motor imagery and analysed for persistence and F/M amplitude ratio.Results: Persistence and F/M amplitude ratios at 1- and 3-min after motor imagery initiation were significantly greater than at baseline. The persistence and F/M amplitude ratio at 5-min after motor imagery initiation, however, was comparable to baseline levels.Conclusion: Therefore, 1 to 3 min of motor imagery is likely sufficient to facilitate the excitability of spinal anterior horn cells.

Acute Flaccid Paralysis and Enteroviral Infections.

The focus of this review is on enterovirus (EV)-associated acute flaccid paralysis (AFP) due to spinal cord anterior horn cell disease. Emphasis is placed on the epidemiology, pathogenesis, diagnosis, treatment, and outcome of AFP caused by polioviruses, vaccine-derived polioviruses, EV-D68, and EV-A71. Since the launch of The Global Polio Eradication Initiative in 1988, the worldwide incidence of polio has been reduced by 99.9%, with small numbers of poliomyelitis cases being reported only in Afghanistan, Pakistan, and Nigeria. With the planned phaseout of oral polio vaccine, vaccine-associated poliomyelitis is also expected to be eliminated. In their place, other EVs, chiefly EV-D68 and EV-A71, have emerged as the principal causes of AFP. There is evidence that the emergence of EV-D68 as a cause of severe respiratory disease and AFP was due to recent genetic virus evolution. Antiviral medications targeting EV-D68, EV-A71, and other EVs will likely be available in the near future. An effective EV-A71 vaccine has been developed, and preliminary investigations suggest an EV-D68 vaccine could be on the horizon. The eradication of poliomyelitis and vaccine-associated poliomyelitis is near, after which other EVs, presently EV-D68 and EV-A71, will be the principle viral causes of AFP. Moving forward, it is essential that EV outbreaks, in particular those associated with neurologic complications, be investigated carefully and the causal strains identified, so that treatment and prevention efforts can be rapidly developed and implemented.

Phosphorylated MTOR in the spinal anterior horn cells of patients with sporadic amyotrophic lateral sclerosis

Phosphorylated MTOR in the spinal anterior horn cells of patients with sporadic amyotrophic lateral sclerosis