Motor Performance Research Articles

Darts fast-learning reduces theta power but is not affected by Hf-tRNS: A behavioral and electrophysiological investigation

Sports trainers have recently shown increasing interest in innovative methods, including transcranial electric stimulation, to enhance motor performance and boost the acquisition of new skills during training. However, studies on the effectiveness of these tools on fast visuomotor learning and brain activity are still limited. In this randomized single-blind, sham-controlled, between-subjects study, we investigated whether a single training session, either coupled or not with 2 mA online high-frequency transcranial random noise stimulation (hf-tRNS) over the bilateral primary motor cortex (M1), would affect dart-throwing performance (i.e., radial error, arm range of motion, and movement variability) in 37 healthy volunteers. In addition, potential neurophysiological correlates were monitored before and after the training through a 32-electrode portable electroencephalogram (EEG). Results revealed that a single training session improved radial error and arm range of motion during the dart-throwing task, but not movement variability. Furthermore, after the training, resting state-EEG data showed a decrease in theta power. Radial error, arm movement, and EEG were not further modulated by hf-tRNS. This indicates that a single training session, regardless of hf-tRNS administration, improves dart-throwing precision and movement accuracy. However, it does not improve movement variability, which might require multiple training sessions (expertise resulting in slow learning). Theta power decrease could describe a more efficient use of cognitive resources (i.e., attention and visuomotor skills) due to the fast dart-throwing learning. Further research could explore different sports by applying longer stimulation protocols and evaluating other EEG variables to enhance our understanding of the lasting impacts of multi-session hf-tRNS on the sensorimotor cortex within the framework of slow learning and training assistance.

Epilepsy Research in the Institute of Physiology of the Czech Academy of Sciences in Prague.

Starting from simple clinical statistics, the spectrum of methods used in epilepsy research in the Institute of Physiology of the Czechoslovak (now Czech) Academy of Sciences progressively increased. Professor Servít used electrophysiological methods for study of brain activity in lower vertebrates, neuropathology was focused on electronmicroscopic study of cortical epileptic focus and ion-sensitive microelectrodes were used for studies of cortical direct current potentials. Developmental studies used electrophysiological methods (activity and projection of cortical epileptic foci, EEG under the influence of convulsant drugs, hippocampal, thalamic and cortical electrical stimulation for induction of epileptic afterdischarges and postictal period). Extensive pharmacological studies used seizures elicited by convulsant drugs (at first pentylenetetrazol but also other GABA antagonists as well as agonists of glutamate receptors). Motor performance and behavior were also studied during brain maturation. The last but not least molecular biology was included into the spectrum of methods. Many original data were published making a background of position of our laboratory in the first line of laboratories interested in brain development.

Carry-Over Effect of Deep Cerebellar Stimulation-Mediated Motor Recovery in a Rodent Model of Traumatic Brain Injury

Background We previously demonstrated that deep brain stimulation (DBS) of lateral cerebellar nucleus (LCN) can enhance motor recovery and functional reorganization of perilesional cortex in rodent models of stroke or TBI. Objective Considering the treatment-related neuroplasticity observed at the perilesional cortex, we hypothesize that chronic LCN DBS-enhanced motor recovery observed will carry-over even after DBS has been deactivated. Methods Here, we directly tested the enduring effects of LCN DBS in male Long Evans rats that underwent controlled cortical impact (CCI) injury targeting sensorimotor cortex opposite their dominant forepaw followed by unilateral implantation of a macroelectrode into the LCN opposite the lesion. Animals were randomized to DBS or sham treatment for 4 weeks during which the motor performance were characterize by behavioral metrics. After 4 weeks, stimulation was turned off, with assessments continuing for an additional 2 weeks. Afterward, all animals were euthanized, and tissue was harvested for further analyses. Results Treated animals showed significantly greater motor improvement across all behavioral metrics relative to untreated animals during the 4-week treatment, with functional gains persisting across 2-week post-treatment. This motor recovery was associated with the increase in CaMKIIα and BDNF positive cell density across perilesional cortex in treated animals. Conclusions LCN DBS enhanced post-TBI motor recovery, the effect of which was persisted up to 2 weeks beyond stimulation offset. Such evidence should be considered in relation to future translational efforts as, unlike typical DBS applications, treatment may only need to be provided until such time as a new function plateau is achieved.

Empirical Advancements in Field Oriented Control for Enhanced Induction Motor Performance in Electric Vehicle

Empirical Advancements in Field Oriented Control for Enhanced Induction Motor Performance in Electric Vehicle

Properties of layer V pyramidal neurons in the primary motor cortex that represent acquired motor skills

Layer V neurons in primary motor cortex (M1) are required for motor skill learning. We analyzed training-induced plasticity using a whole-cell slice patch-clamp technique with a rotor rod task, and found that training induces diverse changes in intrinsic properties and synaptic plasticity in M1 layer V neurons. Although the causal relationship between specific cellular changes and motor performance is unclear, by linking individual motor performance to cellular/synaptic functions, we identified several cellular and synaptic parameters that represent acquired motor skills. With respect to cellular properties, motor performance was positively correlated with resting membrane potential and fast afterhyperpolarization, but not with the membrane resistance, capacitance, or threshold. With respect to synaptic function, the performance was positively correlated with AMPA receptor-mediated postsynaptic currents, but not with GABAA receptor-mediated postsynaptic currents. With respect to live imaging analysis in Thy1-YFP mice, we further demonstrated a cross-correlation between motor performance, spine head volume, and self-entropy per spine. In the present study, we identified several changes in M1 layer V pyramidal neurons after motor training that represent acquired motor skills. Furthermore, training increased extracellular acetylcholine levels known to promote synaptic plasticity, which is correlated with individual motor performance. These results suggest that systematic control of specific intracellular parameters and enhancement of synaptic plasticity in M1 layer V neurons may be useful for improving motor skills.

Effects of muscle energy technique overhold relax on pain and range of motion in patients with post-surgical elbow stiffness

Background. An elbow joint that can move and is stable is important for work, play, and sports. Stiffness in the elbow after surgery is common and can make it difficult to perform daily activities. This is a significant problem for therapy. Therapeutic exercises, especially stretching exercises, are a crucial part of physiotherapy for alleviating elbow stiffness. Muscle Energy Technique (MET) is a manual therapy that uses mild isometric contractions to utilize the muscles’ energy to help with limited limb movement. On the other hand, Proprioceptive Neuromuscular Facilitation (PNF) is one of the best ways to improve motor performance and speed up recovery by increasing the range of motion and flexibility. The goal is to determine how MET over Hold‑Relax affects pain and range of motion when rehabilitating stiffness in the elbow after surgery. Methods. A quasi-experimental study was conducted on 12 patients post-elbow fracture fixation. Group A was given MET, while Group B received the Hold-Relax Technique three times a week for three consecutive weeks after the immobilization period. As baseline treatment, both groups received active ROM exercises. Pain (Visual Analog Scale) and ROM (goniometer) were assessed pre- and post-3 weeks. Results. In the third week, the two treatment groups showed a statistically significant difference in all parametric values (P < 0.05). However, Group B Hold-Relax’s mean difference and paired and unpaired t-test values were greater compared to Group A MET at the end of the third week. Conclusion. This study concludes that implementing PNF stretch (Hold-Relax) in conjunction with conventional treatment techniques in post-surgical stiffness is beneficial in enhancing the subject’s quality of life by reducing pain and restoring ROM. Hence, PNF (Hold-Relax) can be the best treatment option in physiotherapy practice.

Participation Patterns in Leisure Activities of 6- to 8-Year-Old Typically Developing Children in Relation to Their Motor Performance

ABSTRACT The average level of children’s motor performance has decreased in the past decades. Therefore, it is important to identify risk- or enabling factors for motor performance. One such factor could be children’s participation in leisure activities (LA). LA are non-obligatory and intrinsically motivated activities performed during free time. They include physical activities, such as individual and team sports and other types of activities, such as doing crafts, hanging out with friends, and playing musical instruments. The present study explores how participating in different combinations of LA (i.e. participation patterns) are related to children’s motor performance using a person-centered approach. Ninety 6- to 8-year-old typically developing children (57.8% boys) were recruited from six Dutch primary schools. LA participation and motor performance were measured with the Children’s Assessment of Participation and Enjoyment questionnaire and the Movement Assessment Battery for Children-2, respectively. Children were grouped in patterns using Cluster Analysis. Comparisons among patterns were performed with one-way multivariate analysis of variance. As hypothesized, children who participated in a greater variety of LA (i.e., higher participation diversity) and who engaged more frequently in each LA (i.e., higher participation intensity) scored better on manual dexterity, balance, and total motor performance compared to those with lower participation diversity and intensity. Based on these findings, coaches, physical educators, and parents should create opportunities for children to participate in a broad range of LA and to engage in these LA frequently.

Pathology reduction and motor behavior improvement associated with ultrasound-mediated delivery of arctiin to the motor cortex in a mutant SOD1 mouse model of amyotrophic lateral sclerosis

BackgroundAmyotrophic lateral sclerosis (ALS) is marked by the deterioration of both cortical and spinal cord motor neurons. Despite the underlying causes of the disease remain elusive, there has been a growing attention on the well-being of cortical motor neurons in recent times. Focused ultrasound combined with microbubbles (FUS/MB) for opening the blood–brain barrier (BBB) provides a means for drug delivery to specific brain regions, holding significant promise for the treatment of neurological disorders. ObjectivesWe aim to explore the outcomes of FUS/MB-mediated delivery of arctiin (Arc), a natural compound with anti-inflammatory activities, to the cerebral motor cortex area by using a transgenic ALS mouse model. MethodsThe ALS mouse model with the SOD1G93A mutation was used and subjected to daily Arc administration with FUS/MB treatment twice a week. After six-week treatments, the motor performance was assessed by grip strength, wire hanging, and climbing-pole tests. Mouse brains, spinal cords and gastrocnemius muscle were harvested for histological staining. ResultsCompared with the mice given Arc administration only, the combined treatments of FUS/MB with Arc induced further mitigation of the motor function decline, accompanied by improved health of the gastrocnemius muscle. Furthermore, notable neuroprotective effect was evidenced by the amelioration of motor neuron failure in the cortex and lumbar spinal cord. ConclusionThese preliminary results indicated that the combined treatment of FUS/MB and arctiin exerted a potentially beneficial effect on neuromuscular function in the ALS disease.

Residual and enduring effects of cannabis use on cognitive and psychomotor function: A study of adults during unrestricted cannabis use, short-term abstinence, and protracted abstinence.

The impact of cannabis on cognitive and psychomotor function is important to understand, given the role of the endocannabinoid system in these critical processes. The literature has shown robust acute negative effects of cannabis on cognition and psychomotor skills during intoxication, and to a lesser degree, persisting effects following short-term abstinence up to 4 weeks. However, whether these decrements resolve after long-term cessation of use remains unclear. We evaluated cognitive and psychomotor function in 31 adults with current cannabis use during unrestricted use (UNR) and after a 3-day abstinence (RES), 23 adults with former cannabis use (> 90 days abstinent; FU), and 58 nonusing controls (CON) using the cognition and motor batteries of the National Institutes of Health Toolbox. Linear mixed models showed no significant differences in cognitive and motor performance between UNR, RES, and FU groups. Group effects emerged such that CON outperformed UNR on the Oral Reading Recognition Test, and CON outperformed both UNR and RES on the Picture Vocabulary Test. In terms of psychomotor function, FU, RES, and UNR performed better than CON on the Grip Strength Test. In this comprehensive examination of cognitive and psychomotor performance in adults with cannabis use with 3 days to > 90 days of abstinence, our results indicated that the cognitive impacts of chronic, heavy cannabis use are observable during short-term abstinence but remit after > 90 days of abstinence. This highlights widespread impacts of cannabis use abstinence across cognitive and psychomotor domains. Future studies are needed to evaluate whether these effects are also observable with use reduction, as opposed to abstinence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinical correlates of obstructive sleep apnoea in idiopathic normal pressure hydrocephalus.

The pathogenesis of idiopathic normal pressure hydrocephalus (iNPH) remains controversial. Limited studies have indicated a high prevalence of obstructive sleep apnoea (OSA) amongst iNPH patients. The aim was to investigate the clinical correlates of OSA in iNPH patients. In this cross-sectional observational study, consecutive iNPH patients were prospectively enrolled. Evaluations included the iNPH Rating Scale, the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III, the time and number of steps to walk 10 m, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, a complete neuropsychological evaluation, 3-T brain MRI, full-night video-polysomnography, tap test and cerebrospinal fluid (CSF) neurodegeneration biomarkers. Fifty-one patients were screened, of whom 38 met the inclusion criteria. Amongst the recruited patients, 19/38 (50%) exhibited OSA, with 12/19 (63.2%) presenting moderate to severe disorder. OSA+ iNPH patients required more time (p = 0.02) and more steps (p = 0.04) to complete the 10-m walking test, had lower scores on the gait subitem of the iNPH Rating Scale (p = 0.04) and demonstrated poorer performance on specific neuropsychological tests (Rey Auditory Verbal Learning Test immediate recall, p = 0.03, and Rey-Osterrieth Complex Figure, p = 0.01). Additionally, OSA+ iNPH patients had higher levels of total tau (p = 0.02) and phospho-tau (p = 0.03) in their CSF but no statistically significant differences in beta-amyloid (1-42) levels compared to OSA- iNPH patients. Obstructive sleep apnoea is highly prevalent in iNPH patients, particularly at moderate to severe levels. OSA is associated with worse motor and cognitive performance in iNPH. The CSF neurodegeneration biomarker profile observed in OSA+ iNPH patients may reflect OSA-induced impairment of cerebral fluid dynamics.

Employing popular heritage in the Iraqi theatrical actor’s performance of the play

In the history of Iraqi theater, popular heritage has always been a rich and abundant source of inspiration for artists. Heritage is considered an integral part of the cultural and social identity of the Iraqi people, as it carries within it values, traditions, and stories that constitute a large part of the collective consciousness. In this research, we will discuss how to employ popular heritage in the Iraqi theatrical actor’s performance of the play “The Thread and the Bird” as a model, as the actor aims to revive the heritage and present it in a way that is consistent with modern times, which helps to enhance cultural identity and connection to the roots, as popular heritage was used in the play The thread and the bird are touched in many ways, such as language, fashion, music, and dances. And motor performance. Through the above, the researcher will attempt to study this research in four chapters. The first chapter represents the methodological framework of the research problem around the following question: Was the Iraqi actor able to employ the popular heritage according to his motor and vocal tools in presenting the play The Thread and the Bird? Then the importance of the research and its goal through revealing and identifying the most important skills. The performance techniques that are compatible with the characters carrying the popular heritage in presenting the play The Thread and the Sparrow 0, then the limits of the research and definition of terminology. The second chapter, the theoretical framework, includes two sections: the first: the popular heritage (a historical view). The second section: the popular heritage and the performance of the theatrical actor, then what resulted from the theoretical framework. Of indicators, the third chapter includes procedures that include the research community, its sample, the research site, and sample analysis, then the fourth chapter includes results, conclusions, recommendations, and proposals, and the research concludes with sources Keywords: employment, popular heritage, actor’s performance.

A robust evaluation of TDP-43, poly GP, cellular pathology and behavior in a AAV-C9ORF72 (G4C2)66 mouse model.

The G4C2 hexanucleotide repeat expansion in C9ORF72 is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 G4C2 hexanucleotide repeats. Despite displaying key molecular ALS pathological markers including RNA foci, dipeptide repeat (DPR) protein aggregation, p62 positive stress granule formation as well as mild gliosis, the AAV-(G4C2)66 mouse model in this study exhibits negligible neuronal loss, no motor deficits, and functionally unimpaired TAR DNA-binding protein-43 (TDP-43). While our findings indicate and support that this is a robust and pharmacologically tractable model for investigating the molecular mechanisms and cellular consequences of (G4C2) repeat driven DPR pathology, it is not suitable for investigating the development of disease associated neurodegeneration, TDP-43 dysfunction, gliosis, and motor performance. Our findings underscore the complexity of ALS pathogenesis involving genetic mutations and protein dysregulation and highlight the need for more comprehensive model systems that reliably replicate the multifaceted cellular and behavioral aspects of C9-ALS.

Model-free decision-making underlies motor errors in rapid sequential movements under threat

Our movements, especially sequential ones, are usually goal-directed, i.e., coupled with task-level goals. Consequently, cognitive strategies for decision-making and motor performance are likely to influence each other. However, evidence linking decision-making strategies and motor performance remains elusive. Here, we designed a modified version of the two-step task, named the two-step sequential movement task, where participants had to conduct rapid sequential finger movements to obtain rewards (n = 40). In the shock session, participants received an electrical shock if they made an erroneous or slow movement, while in the no-shock session, they only received zero reward. We found that participants who prioritised model-free decision-making committed more motor errors in the presence of the shock stimulus (shock sessions) than those who prioritised model-based decision-making. Using a mediation analysis, we also revealed a strong link between the balance of the model-based and the model-free learning strategies and sequential movement performances. These results suggested that model-free decision-making produces more motor errors than model-based decision-making in rapid sequential movements under the threat of stressful stimuli.

Does music training improve inhibition control in children? A systematic review and meta-analysis

Inhibition control is an essential executive function during children's development, underpinning self-regulation and the acquisition of social and language abilities. This executive function is intensely engaged in music training while learning an instrument, a complex multisensory task requiring monitoring motor performance and auditory stream prioritization. This novel meta-analysis examined music-based training on inhibition control in children. Records from 1980 to 2023 yielded 22 longitudinal studies with controls (N = 1734), including 8 RCTs and 14 others. A random-effects meta-analysis showed that music training improved inhibition control (moderate-to-large effect size) in the RCTs and the superset of twenty-two longitudinal studies (small-to-moderate effect size). Music training plays a privileged role compared to other activities (sports, visual arts, drama) in improving children's executive functioning, with a particular effect on inhibition control. We recommend music training for complementing education and as a clinical tool focusing on inhibition control remediation (e.g., in autism and ADHD).

The Neuroprotective and Anxiolytic Effects of Magnesium Sulfate on Retinal Dopaminergic Neurons in 6-OHDA-Induced Parkinsonian Rats: A Pilot Study.

This study investigates the protective effects of magnesium sulfate on dopamine neurons in the retinas of rats with 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD). Rapidly progressing cognitive decline often precedes or coincides with the motor symptoms associated with PD. PD patients also frequently exhibit visual function abnormalities. However, the specific mechanisms underlying visual dysfunction in PD patients are not yet fully understood. Therefore, this study aims to investigate whether magnesium homeostasis affects dopaminergic neurons in the retina of PD rats. Thirty-six rats were divided into four groups: (1) control, (2) control with magnesium sulfate (control/MgSO4), (3) Parkinson's disease (PD), and (4) Parkinson's disease with magnesium sulfate (PD/MgSO4). The apomorphine-induced (APO) rotation test assessed the success of the PD models. The open-field experiment measured the rats' anxiety levels. Tyrosine hydroxylase (TH) and glutamate levels, indicators of dopamine neuron survival, were detected using immunofluorescence staining. Protein levels of solute carrier family 41 A1 (SCL41A1), magnesium transporter 1 (MagT1), and cyclin M2 (CNNM2) in the retina were analyzed using Western blot. Results showed that, compared to the PD group, rats in the PD/MgSO4 group had improved psychological states and motor performance at two and four weeks post-surgery. The PD/MgSO4 group also exhibited significantly higher TH fluorescence intensity in the left retinas and lower glutamate fluorescence intensity than the PD group. Additional experiments indicated that the protein levels of SLC41A1, MagT1, and CNNM2 were generally higher in the retinas of the PD/MgSO4 group, along with an increase in retinal magnesium ion content. This suggests that magnesium sulfate may reduce glutamate levels and protect dopamine neurons in the retina. Thus, magnesium sulfate might have therapeutic potential for visual functional impairments in PD patients.

Knowledge over Time of Action Codes for Perceived Objects: An Exploratory Study on Developmental Children.

Over the past 20 years, there has been a growing interest in the processing of tool objects, and in the spatial S-R correspondence effects obtained with pictures of manipulable objects. Beyond the original affordance activation account, a location coding account has been proposed for such behavioral effects, which states that the location of the visually salient portion of an object speeds up spatially aligned motor responses and slows down misaligned ones. Furthermore, an additional action coding account has been proposed, according to which it is the direction of the action of the perceived object (e.g., "pouring tea leftward" when the spout of a teapot is leftward-oriented) that biases motor performance. We investigated this action coding account of S-R correspondence effects by comparing the reaction time (RT) performance of two groups: younger (6 to 9 years old) and older (10 to 13 years old) children. We assumed that knowledge of tool objects and the activation of action codes from object perception is proportional to age. Therefore, a larger correspondence effect was hypothesized for the older relative to the younger children's group. Consistently, a 34 ms correspondence effect was observed in the older children relative to the younger ones (18 ms). The results support the view that action direction is a constitutive feature of tool objects, which is subject to experience, and thus, to increasing knowledge over time.

Effect of Phasic Experimental Pain Applied during Motor Preparation or Execution on Motor Performance and Adaptation in a Reaching Task: A Randomized Trial.

Musculoskeletal conditions often involve pain related to specific movements. However, most studies on the impact of experimental pain on motor performance and learning have used tonic pain models. This study aimed to evaluate the effect of experimental phasic pain during the preparation or execution of a reaching task on the acquisition and retention of sensorimotor adaptation. Participants were divided into three groups: no pain, pain during motor preparation, and pain during motor execution. Pain was induced over the scapula with a laser while participants performed a force field adaptation task over two days. To assess the effect of pain on motor performance, two baseline conditions (with or without pain) involving unperturbed pointing movements were also conducted. The results indicated that the timing of the nociceptive stimulus differently affected baseline movement performance. Pain during motor preparation shortened reaction time, while pain during movement execution decreased task performance. However, when these baseline effects were accounted for, no impact of pain on motor adaptation or retention was observed. All groups showed significant improvements in all motor variables for both adaptation and retention. In conclusion, while acute phasic pain during motor preparation or execution can affect the movement itself, it does not interfere with motor acquisition or retention during a motor adaptation task.

Effects of Motor Learning on Corticospinal Tract Excitability During Motor Imagery.

We aimed to examine the effects of motor performance improvements produced by practice on corticospinal tract excitability during motor imagery (MI) of identical movements. Participants performed a motor task with no guidelines displayed on the monitor (performance test); the participants only imagined performing the task without performing the movement (MI test), and the participants performed the power output and then adjusted it (exercise). The output force conditions were 20, 40, and 60% of the maximum voluntary contraction, and the objective was for 21 participants to learn each output force condition. The outcome of the performance test was calculated as the difference between the actual motor output and the target. During the MI test, we applied a single transcranial magnetic stimulation during imagery, assessed the corticospinal tract excitability of the right first dorsal interosseous by motor-evoked potential (MEP) amplitude, and recorded the vividness of the MI in each trial. We evaluated performance and MI before practice (Pre-test), after 150 practice sessions (Post-test 1), and after another 150 practice sessions (Post-test 2). The MEP amplitude was significantly reduced at Post-test 2 compared to Pre-test. The vividness of the MI improved with practice. Corticospinal tract excitability during MI decreased as motor performance improved. Thus, actual motor practice was also reflected in the MI of the exercise. Performance improvement was accompanied by a decrease in redundant activity, enhancing the efficiency and appropriateness of the exercise.

Impacts de l’observation d’actions dans l’amélioration des capacités de performance motrice chez la personne âgée : une revue systématique de littérature

IntroductionAgeing reduced motor performance, which can affect elderly's autonomy. This study aimed to evaluate the impacts of action observation on motor performance in the elderly. MethodsA systematic review was conducted using Pubmed, Cochrane and Science Direct. Participants were healthy or had pathology (neurologic or orthopedic). ResultsTwenty-two articles have been selected (ntotal=666 participants). This review results show that action observation can improve motor performance capacities by changing behavior (+10.91%), by modulating cortico-spinal excitability (+4.84%), and intracerebral neurons activity (+276.47%). ConclusionAction observation can significantly improve motor performance in the elderly. Thus, under certain conditions, it appears to be a relevant adjuvant therapy for the physiotherapist. Further studies seem to be necessary to complete the recommendations about protocol dosage.

Intranasal delivery of small extracellular vesicles reduces the progress of amyotrophic lateral sclerosis and the overactivation of complement-coagulation cascade and NF-ĸB signaling in SOD1G93A mice

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motoneuron degeneration, and effective clinical treatments are lacking. In this study, we evaluated whether intranasal delivery of mesenchymal stem cell–derived small extracellular vesicles (sEVs) is a strategy for ALS therapy using SOD1G93A mice. In vivo tracing showed that intranasally-delivered sEVs entered the central nervous system and were extensively taken up by spinal neurons and some microglia. SOD1G93A mice that intranasally received sEV administration showed significant improvements in motor performances and survival time. After sEV administration, pathological changes, including spinal motoneuron death and synaptic denervation, axon demyelination, neuromuscular junction degeneration and electrophysiological defects, and mitochondrial vacuolization were remarkably alleviated. sEV administration attenuated the elevation of proinflammatory cytokines and glial responses. Proteomics and transcriptomics analysis revealed upregulation of the complement and coagulation cascade and NF-ĸB signaling pathway in SOD1G93A mouse spinal cords, which was significantly inhibited by sEV administration. The changes were further confirmed by detecting C1q and NF-ĸB expression using Western blots. In conclusion, intranasal administration of sEVs effectively delays the progression of ALS by inhibiting neuroinflammation and overactivation of the complement and coagulation cascades and NF-ĸB signaling pathway and is a potential option for ALS therapy.Graphical abstract