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The present study reveals intraepithelial capillaries in the olfactory neuroepithelium of human fetuses aged between 12 and 24 weeks of gestation, which disappear at birth. The area occupied by the intraepithelial capillaries increases significantly with fetal age (0.047 ± 0.014 μm[sup 2] /μm[sup 2] at 12 weeks and 0.101 ± 0.025 μm[sup 2] /μm[sup 2] at 24 weeks) and with the thickness of the epithelium (45.00 ± 6.74 μm at 8 weeks and 64.10 ± 8.51 μm at 24 weeks). The vascularization of the developing neuroepithelium may suggest increased metabolic demand during development and maturation of the olfactory neuroepithelium, and postnatal retreat of capillaries to the underlying lamina propria may suggest diffusion of nutrients and gases from blood vessels into the lamina propria and direct gaseous exchange from the atmosphere.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Most individuals with cervical spinal cord injury (SCI) show increased muscle weakness in the elbow extensor compared to elbow flexor muscles. Although this is a well-known functional deficit, the underlying neural mechanisms remain poorly understood. To address this question, we measured the suppression of voluntary electromyographic activity (svEMG; a measurement thought to reflect changes in intracortical inhibition) by applying low-intensity transcranial magnetic stimulation over the arm representation of the primary motor cortex during 10% of isometric maximal voluntary contraction (MVC) into elbow flexion or extension in individuals with and without chronic cervical SCI. We found that the svEMG latency and duration were not different between the biceps and triceps brachii in controls but prolonged in the triceps in individuals with SCI. The svEMG area was larger in the triceps compared to the biceps in both groups and further increased in SCI participants, suggesting a pronounced intracortical inhibitory input during elbow extension. A negative correlation was found between svEMG area and MVCs indicating that control and SCI participants with lower svEMG area had larger MVCs. The svEMG area was not different between 5% and 30% of MVC, making it less probable that differences in muscle strength between groups contributed to our results. These findings support the existence of strong inhibitory input to corticospinal projections controlling elbow extensor compared to flexor muscles, which is more pronounced after chronic cervical SCI. KEY POINTS: After cervical spinal cord injury (SCI), people often recover function in elbow flexor, but much less in elbow extensor muscles. The neural mechanisms contributing to this difference remain unknown. We measured the suppression of voluntary electromyographic activity (svEMG) elicited through low-intensity transcranial magnetic stimulation of the primary motor cortex (assumed to reflect changes in intracortical inhibition) in the biceps and triceps muscles in controls and individuals with cervical chronic incomplete SCI. We found increased svEMG area in the triceps compared to the biceps in controls and SCI participants, with this measurement being even more pronounced in the triceps after SCI. The svEMG area correlated with maximal voluntary contraction values in both groups, suggesting the people with lesser inhibition had larger motor output. Our results support the presence of strong cortical inhibitory input to corticospinal projections controlling elbow extensor compared to elbow flexors muscles after cervical SCI., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Changes in Hoffmann reflex (H-reflex) exhibit heterogeneity among patients with amyotrophic lateral sclerosis (ALS), likely due to phenotype diversity. Current knowledge primarily focuses on soleus H-reflex, which may demonstrate an initial increase before subsequent decline throughout the disease course. The main objective was to investigate other muscles, to determine whether H-reflex changes could be associated with patient phenotype (onset site, functional disabilities). Additional experiments were performed to elucidate the neurophysiological mechanisms underlying H-reflex modifications. In age- and sex-matched groups of control subjects and patients, we compared H-reflex recruitment curves in soleus, quadriceps, and forearm flexors. Additionally, we examined H-reflex and motor evoked potential (MEP) recruitment curves in quadriceps. Last, to assess potential changes in monosynaptic excitatory postsynaptic potentials (EPSPs) of both peripheral and cortical origins, we analyzed peristimulus time histograms (PSTHs) and peristimulus frequencygrams (PSFs) of single motor units, along with H-reflex occurrence after paired-pulse stimuli. The ratio between maximal amplitudes of H-reflex and direct motor response increased in all muscles, irrespective of disease onset, and was found positively correlated with exaggerated osteotendinous reflexes and spasticity but depressed in patients on riluzole. This finding was accompanied by a reduction in MEP size and no changes in PSTH, PSF, and paired-pulse H-reflex probability. It is speculated that spinal interneurons may compensate for potential depression of monosynaptic EPSPs in ALS. From a clinical perspective, although the added value of H-reflex to osteotendinous reflex evaluation may be limited, it can serve as a valuable quantitative biomarker of pyramidal dysfunction in clinical trials. NEW & NOTEWORTHY Without significant evidence of peripheral denervation, H-reflex enhancement appears to be a widespread phenomenon, regardless of disease onset site. This increase is likely associated with a decrease in inhibitory control over presynaptic transmission of the synapse between muscle group Ia afferents and motoneurons. Although the link to exaggerated osteotendinous reflexes and spasticity implies a restricted role in identifying a pyramidal syndrome, its quantitative aspect positions the H-reflex as a valuable biomarker in clinical trials.

Electrophysiological studies in nonhuman primates reported the existence of strong corticospinal output from the primary motor cortex to distal compared with proximal hindlimb muscles. The extent to which corticospinal output differs across muscles in the leg in humans remains poorly understood. Using transcranial magnetic stimulation over the leg representation of the primary motor cortex, we constructed motor evoked potential (MEP) recruitment curves to measure the resting motor threshold (RMT), maximum MEP amplitude (MEP-max), and slope in the biceps femoris, rectus femoris, tibialis anterior, soleus, and a foot muscle (i.e., abductor hallucis) in intact humans. We found that the RMT was lower and the MEP-max and slope were larger in the abductor hallucis compared with most other muscles tested. In contrast, the RMT was higher and the MEP-max and slope were lower in the biceps femoris compared to all other muscles tested. Corticospinal responses in the rectus femoris, tibialis anterior, and soleus were in between those obtained from other leg muscles, with the soleus having a higher RMT and lower MEP-max and slope than the rectus femoris and tibialis anterior. To examine the origin of increases in corticospinal excitability in the abductor hallucis, we compared short-interval intracortical inhibition (SICI) and F -waves between the abductor hallucis and tibialis anterior. SICI was similar across muscles while the F -wave amplitude was larger in the abductor hallucis compared with the tibialis anterior. These results support a nonuniform distribution of corticospinal output to leg muscles, highlighting that increases in corticospinal excitability in a foot muscle could be related to a spinal origin. NEW & NOTEWORTHY We provide evidence on how corticospinal output differs across muscles in the leg in intact humans. We found that corticospinal responses were larger in a distal intrinsic foot muscle and were smaller in the biceps femoris compared to all other muscles in the leg. Increases in corticospinal excitability to an intrinsic foot muscle could have a spinal origin.

Objective: A motor complete spinal cord injury (SCI) results in the loss of voluntary motor control below the point of injury. Some of these patients can regain partial motor function through inpatient rehabilitation; however, there is currently no biomarker to easily identify which patients have this potential. Evidence indicates that spasticity could be that marker. Patients with motor complete SCI who exhibit spasticity show preservation of descending motor pathways, the pathways necessary for motor signals to be carried from the brain to the target muscle. We hypothesized that the presence of spasticity predicts motor recovery after subacute motor complete SCI., Methods: Spasticity (Modified Ashworth Scale and pendulum test) and descending connectivity (motor evoked potentials) were tested in the rectus femoris muscle in patients with subacute motor complete (n = 36) and motor incomplete (n = 30) SCI. Motor recovery was assessed by using the International Standards for Neurological Classification of Spinal Cord Injury and the American Spinal Injury Association Impairment Scale (AIS). All measurements were taken at admission and discharge from inpatient rehabilitation., Results: We found that motor complete SCI patients with spasticity improved in motor scores and showed AIS conversion to either motor or sensory incomplete. Conversely, patients without spasticity showed no changes in motor scores and AIS conversion. In incomplete SCI patients, motor scores improved and AIS conversion occurred regardless of spasticity., Interpretation: These findings suggest that spasticity represents an easy-to-use clinical outcome that might help to predict motor recovery after severe SCI. This knowledge can improve inpatient rehabilitation effectiveness for motor complete SCI patients. ANN NEUROL 2023., (© 2023 American Neurological Association.)

Objective: Spinal cord injury (SCI) damages synaptic connections between corticospinal axons and motoneurons of many muscles, resulting in devastating paralysis. We hypothesized that strengthening corticospinal-motoneuronal synapses at multiple spinal cord levels through Hebbian plasticity (i.e., "neurons that fire together, wire together") promotes recovery of leg and arm function., Methods: Twenty participants with chronic SCI were randomly assigned to receive 20 sessions of Hebbian or sham stimulation targeting corticospinal-motoneuronal synapses of multiple leg muscles followed by exercise. Based on the results from this study, in a follow-up prospective study, 11 more participants received 40 sessions of Hebbian stimulation targeting corticospinal-motoneuronal synapses of multiple arm and leg muscles followed by exercise. During Hebbian stimulation sessions, 180 paired pulses elicited corticospinal action potentials by magnetic (motor cortex) and/or electrical (thoracic spine) stimulation allowing volleys to arrive at the spinal cord 1-2 milliseconds before motoneurons were activated retrogradely via bilateral electrical stimulation (brachial plexus, ulnar, femoral, and common peroneal nerves) for biceps brachii, first dorsal interosseous, quadriceps femoris, and tibialis anterior muscles as needed., Results: We found in our randomized study that participants receiving Hebbian stimulation improved their walking speed and corticospinal function to a greater extent than individuals receiving sham stimulation. In agreement, prospective study participants improved their grasping and walking, corticospinal function, and quality of life metrics, exhibiting greater improvements with more sessions that persisted 9-month post-therapy., Interpretation: Our findings suggest that multisite Hebbian stimulation, informed by the physiology of the corticospinal system, represents an effective strategy to promote functional recovery following SCI. ANN NEUROL 2023;93:1198-1213., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Spasticity is one of the most common symptoms manifested following spinal cord injury (SCI). The aim of this study was to assess spasticity in individuals with subacute and chronic SCI with different injury severity, standardizing the time and assessments of spasticity. We tested 110 individuals with SCI classified by the American Spinal Injury Association Impairment Scale (AIS) as either motor complete (AIS A and B; subacute, n = 25; chronic, n = 33) or motor incomplete (AIS C and D; subacute, n = 23; chronic, n = 29) at a similar time after injury (subacute, ∼1 mo after injury during inpatient rehabilitation and chronic, ≥1 yr after injury) using clinical (modified Ashworth scale) and kinematic (pendulum test) outcomes to assess spasticity in the quadriceps femoris muscle. Using both methodologies, we found that among individuals with subacute motor complete injuries, only a minority showed spasticity, whereas the majority exhibited no spasticity. This finding stands in contrast to individuals with subacute motor incomplete injury, where both methodologies revealed that a majority exhibited spasticity, whereas a minority exhibited no spasticity. In chronic injuries, most individuals showed spasticity regardless of injury severity. Notably, when spasticity was present, its magnitude was similar across injury severity in both subacute and chronic injuries. Our results suggest that the prevalence, not the magnitude, of spasticity differs between individuals with motor complete and incomplete SCI in the subacute and chronic stages of the injury. We thus argue that considering the "presence of spasticity" might help the stratification of participants with motor complete injuries for clinical trials. NEW & NOTEWORTHY The prevalence of spasticity in humans with SCI remains poorly understood. Using kinematic and clinical outcomes, we examined spasticity in individuals with subacute and chronic injuries of different severity. We found that spasticity in the quadriceps femoris muscle was more prevalent among individuals with subacute motor incomplete than in those with motor complete injuries. However, in a different group of individuals with chronic injuries, no differences were found in the prevalence of spasticity across injury severity.

Aim: Adaptive mechanisms in spinal circuits are likely involved in homeostatic responses to maintain motor output in amyotrophic lateral sclerosis. Given the role of Renshaw cells in regulating the motoneuron input/output gain, we investigated the modulation of heteronymous recurrent inhibition., Methods: Electrical stimulations were used to activate recurrent collaterals resulting in the Hoffmann reflex depression. Inhibitions from soleus motor axons to quadriceps motoneurons, and vice versa, were tested in 38 patients and matched group of 42 controls., Results: Compared with controls, the mean depression of quadriceps reflex was larger in patients, while that of soleus was smaller, suggesting that heteronymous recurrent inhibition was enhanced in quadriceps but reduced in soleus. The modulation of recurrent inhibition was linked to the size of maximal direct motor response and lower limb dysfunctions, suggesting a significant relationship with the integrity of the target motoneuron pool and functional abilities. No significant link was found between the integrity of motor axons activating Renshaw cells and the level of inhibition. Enhanced inhibition was particularly observed in patients within the first year after symptom onset and with slow progression of lower limb dysfunctions. Normal or reduced inhibitions were mainly observed in patients with motor weakness first in lower limbs and greater dysfunctions in lower limbs., Conclusion: We provide the first evidence for enhanced recurrent inhibition and speculate that Renshaw cells might have transient protective role on motoneuron by counteracting hyperexcitability at early stages. Several mechanisms likely participate including cortical influence on Renshaw cell and reinnervation by slow motoneurons., (© 2022 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Key Points: Damage to corticospinal axons has implications for the development of spasticity following spinal cord injury (SCI). Here, we examined to what extent residual corticospinal connections and spasticity are present in muscles below the injury (quadriceps femoris and soleus) in humans with motor complete thoracic SCI. We found three distinct subgroups of people: participants with spasticity and corticospinal responses in the quadriceps femoris and soleus; participants with spasticity and corticospinal responses in the quadriceps femoris only; and participants with no spasticity or corticospinal responses in either muscle. Spasticity and corticospinal responses were present in the quadriceps but never only in the soleus muscle, suggesting a proximal to distal gradient of symptoms of hyperreflexia. These results suggest that concomitant patterns of residual corticospinal connectivity and spasticity exist in humans with motor complete SCI and that a clinical examination of spasticity might be a good predictor of residual descending motor pathways in people with severe paralysis., Abstract: The loss of corticospinal axons has implications for the development of spasticity following spinal cord injury (SCI). However, the extent to which residual corticospinal connections and spasticity are present across muscles below the injury remains unknown. To address this question, we tested spasticity using the Modified Ashworth Scale and transmission in the corticospinal pathway by examining motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the leg motor cortex (cortical MEPs) and by direct activation of corticospinal axons by electrical stimulation over the thoracic spine (thoracic MEPs), in the quadriceps femoris and soleus muscles, in 30 individuals with motor complete thoracic SCI. Cortical MEPs were also conditioned by thoracic electrical stimulation at intervals allowing their summation or collision. We found three distinct subgroups of participants: 47% showed spasticity in the quadriceps femoris and soleus muscles; 30% showed spasticity in the quadriceps femoris muscle only; and 23% showed no spasticity in either muscle. Although cortical MEPs were present only in the quadriceps in participants with spasticity, thoracic MEPs were present in both muscles when spasticity was present. Thoracic electrical stimulation facilitated and suppressed cortical MEPs, showing that both forms of stimulation activated similar corticospinal axons. Cortical and thoracic MEPs correlated with the degree of spasticity in both muscles. These results provide the first evidence that related patterns of residual corticospinal connectivity and spasticity exist in muscles below the injury after motor complete thoracic SCI and highlight that a clinical examination of spasticity can predict residual corticospinal connectivity after severe paralysis., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)

Humans with cervical spinal cord injury (SCI) often recover voluntary control of elbow flexors and, to a much lesser extent, elbow extensor muscles. The neural mechanisms underlying this asymmetrical recovery remain unknown. Anatomical and physiological evidence in animals and humans indicates that corticospinal and reticulospinal pathways differentially control elbow flexor and extensor motoneurons; therefore, it is possible that reorganization in these pathways contributes to the asymmetrical recovery of elbow muscles after SCI. To test this hypothesis, we examined motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the arm representation of the primary motor cortex, maximal voluntary contractions, the StartReact response (a shortening in reaction time evoked by a startling stimulus), and the effect of an acoustic startle cue on MEPs elicited by cervicomedullary stimulation (CMEPs) on biceps and triceps brachii in males and females with and without chronic cervical incomplete SCI. We found that SCI participants showed similar MEPs and maximal voluntary contractions in biceps but smaller responses in triceps compared with controls, suggesting reduced corticospinal inputs to elbow extensors. The StartReact and CMEP facilitation was larger in biceps but similar to controls in triceps, suggesting enhanced reticulospinal inputs to elbow flexors. These findings support the hypothesis that the recovery of biceps after cervical SCI results, at least in part, from increased reticulospinal inputs and that the lack of these extra inputs combined with the loss of corticospinal drive contribute to the pronounced weakness found in triceps. SIGNIFICANCE STATEMENT Although a number of individuals with cervical incomplete spinal cord injury show limited functional recovery of elbow extensors compared with elbow flexor muscles, to date, the neural mechanisms underlying this asymmetrical recovery remain unknown. Here, we provide for the first time evidence for increased reticulospinal inputs to biceps but not triceps brachii and loss of corticospinal drive to triceps brachii in humans with tetraplegia. We propose that this reorganization in descending control contributes to the asymmetrical recovery between elbow flexor and extensor muscles after cervical spinal cord injury., (Copyright © 2020 the authors.)

Spasticity is one of the most common symptoms present in humans with spinal cord injury (SCI); however, its clinical assessment remains underdeveloped. The purpose of the study was to examine the contribution of passive muscle stiffness and active spinal reflex mechanisms to clinical outcomes of spasticity after SCI. It is important that passive and active contributions to increased muscle stiffness are distinguished to make appropriate decisions about antispastic treatments and to monitor its effectiveness. To address this question, we combined biomechanical and electrophysiological assessments of ankle plantarflexor muscles bilaterally in individuals with and without chronic SCI. Spasticity was assessed using the Modified Ashworth Scale (MAS) and a self-reported questionnaire. We performed slow and fast dorsiflexion stretches of the ankle joint to measure passive muscle stiffness and reflex-induced torque using a dynamometer and the soleus H reflex using electrical stimulation over the posterior tibial nerve. All SCI participants reported the presence of spasticity. While 96% of them reported higher spasticity on one side compared with the other, the MAS detected differences across sides in only 25% of the them. Passive muscle stiffness and the reflex-induced torque were larger in SCI compared with controls more on one side compared with the other. The soleus stretch reflex, but not the H reflex, was larger in SCI compared with controls and showed differences across sides, with a larger reflex in the side showing a higher reflex-induced torque. MAS scores were not correlated with biomechanical and electrophysiological outcomes. These findings provide evidence for bilateral and asymmetric contributions of passive and active ankle plantar flexors stiffness to spasticity in humans with chronic SCI and highlight a poor agreement between a self-reported questionnaire and the MAS for detecting asymmetries in spasticity across sides. NEW & NOTEWORTHY Spasticity affects a number of people with spinal cord injury (SCI). Using biomechanical, electrophysiological, and clinical assessments, we found that passive muscle properties and active spinal reflex mechanisms contribute bilaterally and asymmetrically to spasticity in ankle plantarflexor muscles in humans with chronic SCI. A self-reported questionnaire had poor agreement with the Modified Ashworth Scale in detecting asymmetries in spasticity. The nature of these changes might contribute to the poor sensitivity of clinical exams.

Objective: The excitability of the lower motoneurone pool is traditionally tested using the H reflex and a constant-stimulus paradigm, which measures changes in the amplitude of the reflex response. This technique has limitations because reflex responses of different size must involve the recruitment or inhibition of different motoneurones. The threshold-tracking technique ensures that the changes in excitability occur for an identical population of motoneurones. We aimed to assess this technique and then apply it in patients with motor neurone disease (MND)., Methods: The threshold-tracking approach was assessed in 17 healthy subjects and 11 patients with MND. The soleus H reflex was conditioned by deep peroneal nerve stimulation producing reciprocal Ia and so-called D1 and D2 inhibitions, which are believed to reflect presynaptic inhibition of soleus Ia afferents., Results: Threshold tracking was quicker than the constant-stimulus technique and reliable, properties that may be advantageous for clinical studies. D1 inhibition was significantly reduced in patients with MND., Conclusions: Threshold tracking is useful and may be preferable under some conditions for studying the excitability of the motoneurone pool. The decreased D1 inhibition in the patients suggests that presynaptic inhibition may be reduced in MND., Significance: Reduced presynaptic inhibition could be evidence of an interneuronopathy in MND. It is possible that the hyperreflexia is a spinal pre-motoneuronal disorder, and not definitive evidence of corticospinal involvement in MND., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. All rights reserved.)

Damage to the corticospinal and reticulospinal tract has been associated with spasticity in humans with upper motor neuron lesions. We hypothesized that these descending motor pathways distinctly contribute to the control of a spastic muscle in humans with incomplete spinal cord injury (SCI). To test this hypothesis, we examined motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the leg representation of the primary motor cortex, maximal voluntary contractions (MVCs), and the StartReact response (shortening in reaction time evoked by a startling stimulus) in the quadriceps femoris muscle in male and females with and without incomplete SCI. A total of 66.7% of the SCI participants showed symptoms of spasticity, whereas the other 33.3% showed no or low levels of spasticity. We found that participants with spasticity had smaller MEPs and MVCs and larger StartReact compared with participants with no or low spasticity and control subjects. These results were consistently present in spastic subjects but not in the other populations. Clinical scores of spasticity were negatively correlated with MEP-max and MVC values and positively correlated with shortening in reaction time. These findings provide evidence for lesser corticospinal and larger reticulospinal influences to spastic muscles in humans with SCI and suggest that these imbalanced contributions are important for motor recovery. SIGNIFICANCE STATEMENT Although spasticity is one of the most common symptoms manifested in humans with spinal cord injury (SCI) to date, its mechanisms of action remain poorly understood. We provide evidence, for the first time, of imbalanced contributions of the corticospinal and reticulospinal tract to control a spastic muscle in humans with chronic incomplete SCI. We found that participants with SCI with spasticity showed small corticospinal responses and maximal voluntary contractions and larger reticulospinal gain compared with participants with no or low spasticity and control subjects. These results were consistently present in spastic subjects but not in the other populations. We showed that imbalanced corticospinal and reticulospinal tract contributions are more pronounced in participants with chronic incomplete SCI with lesser recovery., (Copyright © 2019 the authors.)

Objective: Spasticity is one of the most common symptoms manifested in humans with spinal cord injury (SCI). The neural mechanisms contributing to its development are not yet understood. Using neurophysiological and imaging techniques, we examined the influence of residual descending motor pathways on spasticity in humans with SCI., Methods: We measured spasticity in 33 individuals with motor complete SCI (determined by clinical examination) without preservation of voluntary motor output in the quadriceps femoris muscle. To examine residual descending motor pathways, we used magnetic and electrical stimulation over the leg motor cortex to elicit motor evoked potentials (MEPs) in the quadriceps femoris muscle and structural magnetic resonance imaging to measure spinal cord atrophy., Results: We found that 60% of participants showed symptoms of spasticity, whereas the other 40% showed no spasticity, demonstrating the presence of 2 clear subgroups of humans with motor complete SCI. MEPs were only present in individuals who had spasticity, and MEP size correlated with the severity of spasticity. Spinal cord atrophy was greater in nonspastic compared with spastic subjects. Notably, the degree of spared tissue in the lateral regions of the spinal cord was positively correlated with the severity of spasticity, indicating preservation of white matter related to motor tracts when spasticity was present., Interpretation: These results support the hypothesis that preservation of descending motor pathways influences spasticity in humans with motor complete SCI; this knowledge might help the rehabilitation and assessment of people with SCI. ANN NEUROL 2019., (© 2019 American Neurological Association.)

The increased contaminants caused by anthropogenic activities in the environment and the importance of finding pathways to reduce pollution caused the silicon application to be considered an important detoxification agent. Silicon, as a beneficial element, plays an important role in amelioration of abiotic stress, such as an extreme dose of heavy metal in plants. There are several mechanisms involved in silicon mediation in plants, including the reduction of heavy metal uptake by plants, changing pH value, formation of Si heavy metals, and stimulation of enzyme activity, which can work by chemical and physical pathways. The aim of this paper is to investigate the major silicon-related mechanisms that reduce the toxicity of heavy metals in plants and then to assess the role of silicon in increasing the antioxidant enzyme and nonenzyme activities to protect the plant cell.

Objectives: Infraclinical sensory alterations have been reported at early stages of amyotrophic lateral sclerosis (ALS). While previous studies mainly focused on early somatosensory evoked potentials (SEPs), late SEPs, which reflect on cortical pathways involved in cognitive-motor functions, are relatively underinvestigated. Early and late SEPs were compared to assess their alterations in ALS., Methods: Median and ulnar nerves were electrically stimulated at the wrist, at 9 times the perceptual threshold, in 21 ALS patients without clinical evidence of sensory deficits, and 21 age- and gender-matched controls. SEPs were recorded at the Erb point using surface electrodes and using a needle inserted in the scalp, in front of the primary somatosensory area (with reference electrode on the ear lobe)., Results: Compared to controls, ALS patients showed comparable peripheral (N9) and early cortical component (N20, P25, N30) reductions, while the late cortical components (N60, P100) were more depressed than the early ones., Conclusions: The peripheral sensory alteration likely contributed to late SEP depression to a lesser extent than that of early SEPs., Significance: Late SEPs may provide new insights on abnormal cortical excitability affecting brain areas involved in cognitive-motor functions., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Inhibitory propriospinal neurons with diffuse projections onto upper limb motoneurons have been revealed in humans using peripheral nerve stimulation. This system is supposed to mediate descending inhibition to motoneurons, to prevent unwilling muscle activity. However, the corticospinal control onto inhibitory propriospinal neurons has never been investigated so far in humans. We addressed the question whether inhibitory cervical propriospinal neurons receive corticospinal inputs from primary motor (M1) and ventral premotor areas (PMv) using spatial facilitation method. We have stimulated M1 or PMv using transcranial magnetic stimulation (TMS) and/or median nerve whose afferents are known to activate inhibitory propriospinal neurons. Potential input convergence was evaluated by studying the change in monosynaptic reflexes produced in wrist extensor electromyogram (EMG) after isolated and combined stimuli in 17 healthy subjects. Then, to determine whether PMv controlled propriospinal neurons directly or through PMv-M1 interaction, we tested the connectivity between PMv and propriospinal neurons after a functional disruption of M1 produced by paired continuous theta burst stimulation (cTBS). TMS over M1 or PMv produced reflex inhibition significantly stronger on combined stimulations, compared to the algebraic sum of effects induced by isolated stimuli. The extra-inhibition induced by PMv stimulation remained even after cTBS which depressed M1 excitability. The extra-inhibition suggests the existence of input convergence between peripheral afferents and corticospinal inputs onto inhibitory propriospinal neurons. Our results support the existence of direct descending influence from M1 and PMv onto inhibitory propriospinal neurons in humans, possibly though direct corticospinal or via reticulospinal inputs., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Objective: Subclinical sensory defect can be detected early in ALS. Its impact on spinal excitability was assessed by testing the effects produced by intrinsic hand muscle afferents in triceps brachii motoneurons of patients with distal motor weakness., Methods: TMS was applied over the motor cortex to produce MEP in contralateral triceps during tonic contraction. The intensity varied to compare the full MEP recruitment curve in ALS patients and controls. Then, median and ulnar nerve stimulations at wrist level were combined to TMS to compare the resulting changes in MEP size in both groups., Results: MEP recruitment curves were similar in both groups but MEP threshold was significantly higher in ALS. At sub-threshold intensity for MEP, TMS depressed more EMG activity in ALS than in controls. Nerve stimuli increased MEP size in both groups with similar temporal characteristics but the level of facilitation was stronger in ALS., Conclusion: Cortical hypo-excitability in ALS was accompanied with stronger intra-cortical inhibition in triceps area. While the corticospinal and peripheral inputs were likely depressed, spinal motoneuron response to combined inputs was particularly enhanced in ALS., Significance: Spinal network properties likely compensate for depression of afferent inputs leading to motoneuron hyper-excitability, which may contribute to excito-toxicity., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Reciprocal Ia inhibition constitutes a key segmental neuronal pathway for coordination of antagonist muscles. In this study, we investigated the soleus H-reflex and reciprocal inhibition exerted from flexor group Ia afferents on soleus motoneurons during standing and walking in 15 healthy subjects following transcranial magnetic stimulation (TMS). The effects of separate TMS or deep peroneal nerve (DPN) stimulation and the effects of combined (TMS + DPN) stimuli on the soleus H-reflex were assessed during standing and at mid- and late stance phases of walking. Subthreshold TMS induced short-latency facilitation on the soleus H-reflex that was present during standing and at midstance but not at late stance of walking. Reciprocal inhibition was increased during standing and at late stance but not at the midstance phase of walking. The effects of combined TMS and DPN stimuli on the soleus H-reflex significantly changed between tasks, resulting in an extra facilitation of the soleus H-reflex during standing and not during walking. Our findings indicate that corticospinal inputs and Ia inhibitory interneurons interact at the spinal level in a task-dependent manner, and that corticospinal modulation of reciprocal Ia inhibition is stronger during standing than during walking., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Small RGK GTPases, Rad, Gem, Rem1, and Rem2, are potent inhibitors of high-voltage-activated (HVA) Ca(2+) channels expressed in heterologous expression systems. However, the role of this regulation has never been clearly demonstrated in the nervous system. Using transcriptional analysis, we show that peripheral nerve injury specifically upregulates Gem in mice dorsal root ganglia. Following nerve injury, protein expression was increased in ganglia and peripheral nerve, mostly under its phosphorylated form. This was confirmed in situ and in vitro in dorsal root ganglia sensory neurons. Knockdown of endogenous Gem, using specific small-interfering RNA (siRNA), increased the HVA Ca(2+) current only in the large-somatic-sized neurons. Combining pharmacological analysis of the HVA Ca(2+) currents together with Gem siRNA-transfection of larger sensory neurons, we demonstrate that only the P/Q-type Ca(2+) channels were enhanced. In vitro analysis of Gem affinity to various CaVβx-CaV2.x complexes and immunocytochemical studies of Gem and CaVβ expression in sensory neurons suggest that the specific inhibition of the P/Q channels relies on both the regionalized upregulation of Gem and the higher sensitivity of the endogenous CaV2.1-CaVβ4 pair in a subset of sensory neurons including the proprioceptors. Finally, pharmacological inhibition of P/Q-type Ca(2+) current reduces neurite branching of regenerating axotomized neurons. Taken together, the present results indicate that a Gem-dependent P/Q-type Ca(2+) current inhibition may contribute to general homeostatic mechanisms following a peripheral nerve injury.

Crossed reflex action mediated by muscle spindle afferent inputs has recently been revealed in humans. This raised the question of whether a complex spinal network involving commissural interneurons receiving inputs from proprioceptors and suprasegmental structures, as described in cats, persists in humans and contributes to the interlimb coordination during movement. First, we investigated the neurophysiological mechanisms underlying crossed reflex action between ankle plantar flexors and its corticospinal control from primary motor cortex. Second, we studied its modulation during motor tasks. We observed crossed inhibition in contralateral soleus motoneurons occurring with about 3 ms central latency, which is consistent with spinal transmission through oligosynaptic pathway. The early phase of inhibition was evoked with lower stimulus intensity than the late phase, suggesting mediation by group I and group II afferents, respectively. The postsynaptic origin of crossed inhibition is confirmed by the finding that both H-reflex and motor-evoked potential were reduced upon conditioning stimulation. Transcranial magnetic stimulation over ipsilateral and contralateral primary motor cortex reduced crossed inhibition, especially its late group II part. Last, late group II crossed inhibition was particularly depressed during motor tasks, especially when soleus was activated during the walking stance phase. Our results suggest that both group I and group II commissural interneurons participate in crossed reflex actions between ankle plantar flexors. Neural transmission at this level is depressed by descending inputs activated by transcranial magnetic stimulation over the primary motor cortex or during movement. The specific modulation of group II crossed inhibition suggests control from monoaminergic midbrain structures and its role for interlimb coordination during locomotion.

Objective: To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients., Materials and Methods: After a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ⊥, λ//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score., Results: At MRI1, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI1, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI1 to MRI2, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change., Conclusion: Atrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs.

The cation-chloride cotransporter NKCC1 plays a fundamental role in the central and peripheral nervous systems by setting the value of intracellular chloride concentration. Following peripheral nerve injury, NKCC1 phosphorylation-induced chloride accumulation contributes to neurite regrowth of sensory neurons. However, the molecules and signaling pathways that regulate NKCC1 activity remain to be identified. Functional analysis of cotransporter activity revealed that inhibition of endogenously produced cytokine interleukin-6 (IL-6), with anti-mouse IL-6 antibody or in IL-6⁻/⁻ mice, prevented chloride accumulation in a subset of axotomized neurons. Nerve injury upregulated the transcript and protein levels of IL-6 receptor in myelinated, TrkB-positive sensory neurons of murine lumbar dorsal root ganglia. Expression of phospho-NKCC1 was observed mainly in sensory neurons expressing IL-6 receptor and was absent from IL-6⁻/⁻ dorsal root ganglia. The use of IL-6 receptor blocking-function antibody or soluble IL-6 receptor, together with pharmacological inhibition of Janus kinase, confirmed the role of neuronal IL-6 signaling in chloride accumulation and neurite growth of a subset of axotomized sensory neurons. Cell-specific expression of interleukin-6 receptor under pathophysiological conditions is therefore a cellular response by which IL-6 contributes to nerve regeneration through neuronal NKCC1 phosphorylation and chloride accumulation.

The afferent innervation of the suprarenal gland was studied by using a fluorescent tract tracer in the adult albino rat. The left suprarenal gland was injected slowly with 5 microl of 2% aqueous suspension of Fast blue. After a survival period of 4-5 days, the dorsal root ganglia were dissected out and 15-microm-thick plastic (JB 4) sections were examined under the fluorescent microscope. The labelled neurons were seen from the third thoracic to second lumbar dorsal root ganglia, ipsilateral to the site of injection with maximum concentration from T6 to T11. These primary sensory neurons were round to oval in shape, varied from 7 microm to 40 microm in size, and were distributed randomly in the dorsal root ganglia. The labelling of the primary sensory neurons in the dorsal root ganglia confirms the presence of sensory nerve endings in the suprarenal gland that may be responsible for the vascular distension and hormonal release.