Flexible circumferential bioelectronics to enable 360-degree recording and stimulation of the spinal cord.

The spinal cord is crucial for transmitting motor and sensory information between the brain and peripheral systems. Spinal cord injuries can lead to severe consequences, including paralysis and autonomic dysfunction. We introduce thin-film, flexible electronics for circumferential interfacing with the spinal cord. This method enables simultaneous recording and stimulation of dorsal, lateral, and ventral tracts with a single device. Our findings include successful motor and sensory signal capture and elicitation in anesthetized rats, a proof-of-concept closed-loop system for bridging complete spinal cord injuries, and device safety verification in freely moving rodents. Moreover, we demonstrate potential for human application through a cadaver model. This method sees a clear route to the clinic by using materials and surgical practices that mitigate risk during implantation and preserve cord integrity.

An evaluation of the effects of localised skin cooling on microvascular, inflammatory, structural, and perceptual responses to sustained mechanical loading of the sacrum: A study protocol.

This study protocol aims to investigate how localised cooling influences the skin's microvascular, inflammatory, structural, and perceptual tolerance to sustained mechanical loading at the sacrum, evaluating factors such as morphology, physiology, and perceptual responses. The protocol will be tested on individuals of different age, sex, skin tone and clinical status, using a repeated-measure design with three participants cohorts: i) young healthy (n = 35); ii) older healthy (n = 35); iii) spinal cord injured (SCI, n = 35). Participants will complete three testing sessions during which their sacrum will be mechanically loaded (60 mmHg; 45 min) and unloaded (20 min) with a custom-built thermal probe, causing pressure-induced ischemia and post-occlusive reactive hyperaemia. Testing sessions will differ by the probe's temperature, which will be set to either 38°C (no cooling), 24°C (mild cooling), or 16°C (strong cooling). We will measure skin blood flow (via Laser Doppler Flowmetry; 40 Hz); pro- and anti-inflammatory biomarkers in skin sebum (Sebutape); structural skin properties (Optical Coherence Tomography); and ratings of thermal sensation, comfort, and acceptance (Likert Scales); throughout the loading and unloading phases. Changes in post-occlusive reactive hyperaemia will be considered as the primary outcome and data will be analysed for the independent and interactive effects of stimuli's temperature and of participant group on within- and between-subject mean differences (and 95% Confidence Intervals) in peak hyperaemia, by means of a 2-way mixed model ANOVA (or Friedman). Regression models will also be developed to assess the relationship between absolute cooling temperatures and peak hyperaemia. Secondary outcomes will be within- and between-subject mean changes in biomarkers' expression, skin structural and perceptual responses. This analysis will help identifying physiological and perceptual thresholds for the protective effects of cooling from mechanically induced damage underlying the development of pressure ulcers in individuals varying in age and clinical status.

Contribution of mechanoreceptors to spinal cord injury-induced mechanical allodynia.

ABSTRACT: Evidence from previous studies supports the concept that spinal cord injury (SCI)-induced neuropathic pain (NP) has its neural roots in the peripheral nervous system. There is uncertainty about how and to which degree mechanoreceptors contribute. Sensorimotor activation-based interventions (eg, treadmill training) have been shown to reduce NP after experimental SCI, suggesting transmission of pain-alleviating signals through mechanoreceptors. The aim of the present study was to understand the contribution of mechanoreceptors with respect to mechanical allodynia in a moderate mouse contusion SCI model. After genetic ablation of tropomyosin receptor kinase B expressing mechanoreceptors before SCI, mechanical allodynia was reduced. The identical genetic ablation after SCI did not yield any change in pain behavior. Peptidergic nociceptor sprouting into lamina III/IV below injury level as a consequence of SCI was not altered by either mechanoreceptor ablation. However, skin-nerve preparations of contusion SCI mice 7 days after injury yielded hyperexcitability in nociceptors, not in mechanoreceptors, which makes a substantial direct contribution of mechanoreceptors to NP maintenance unlikely. Complementing animal data, quantitative sensory testing in human SCI subjects indicated reduced mechanical pain thresholds, whereas the mechanical detection threshold was not altered. Taken together, early mechanoreceptor ablation modulates pain behavior, most likely through indirect mechanisms. Hyperexcitable nociceptors seem to be the main drivers of SCI-induced NP. Future studies need to focus on injury-derived factors triggering early-onset nociceptor hyperexcitability, which could serve as targets for more effective therapeutic interventions.

Dissecting Genetic Mechanisms of Differential Locomotion, Depression, and Allodynia after Spinal Cord Injury in Three Mouse Strains.

Strain differences have been reported for motor behaviors, and only a subset of spinal cord injury (SCI) patients develop neuropathic pain, implicating genetic or genomic contribution to this condition. Here, we evaluated neuropsychiatric behaviors in A/J, BALB/c, and C57BL/6 male mice and tested genetic or genomic alterations following SCI. A/J and BALB/c naive mice showed significantly less locomotor activity and greater anxiety-like behavior than C57BL/6 mice. Although SCI elicited locomotor dysfunction, C57BL/6 and A/J mice showed the best and the worst post-traumatic recovery, respectively. Mild (m)-SCI mice showed deficits in gait dynamics. All moderate/severe SCI mice exhibited similar degrees of anxiety/depression. mSCI in BALB/c and A/J mice resulted in depression, whereas C57BL/6 mice did not exhibit depression. mSCI mice had significantly lower mechanical thresholds than their controls, indicating high cutaneous hypersensitivity. C57BL/6, but not A/J and BLAB/c mice, showed significantly lower heat thresholds than their controls. C57BL/6 mice exhibited spontaneous pain. RNAseq showed that genes in immune responses and wound healing were upregulated, although A/J mice showed the largest increase. The cell cycle and the truncated isoform of trkB genes were robustly elevated in SCI mice. Thus, different genomics are associated with post-traumatic recovery, underscoring the likely importance of genetic factors in SCI.

Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial.

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472 .

Injectable conductive hydrogel remodeling microenvironment and mimicking neuroelectric signal transmission after spinal cord injury.

Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo, SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments.

Clustering index analysis on EMG-Torque relation-based representation of complex neuromuscular changes after spinal cord injury.

Spinal cord injury (SCI) resulting in complex neuromuscular pathology is not sufficiently well understood. To better quantify neuromuscular changes after SCI, this study uses a clustering index (CI) method for surface electromyography (sEMG) clustering representation to investigate the relation between sEMG and torque in SCI survivors. The sEMG signals were recorded from 13 subjects with SCI and 13 gender-age matched able-bodied subjects during isometric contraction of the biceps brachii muscle at different torque levels using a linear electrode array. Two torque representations, maximum voluntary contraction (MVC%) and absolute torque, were used. CI values were calculated for sEMG. Regression analyses were performed on CI values and torque levels of elbow flexion, revealing a strong linear relationship. The slopes of regressions between SCI survivors and control subjects were compared. The findings indicated that the range of distribution of CI values and slopes was greater in subjects with SCI than in control subjects (p < 0.05). The increase or decrease in slope was also observed at the individual level. This suggests that the CI and its sEMG clustering-torque relation may serve as valuable quantitative indicators for determining neuromuscular lesions after SCI, contributing to the development of effective rehabilitation strategies for improving motor performance.

Gait Training-Based Motor Imagery and EEG Neurofeedback in Lokomat: A Clinical Intervention With Complete Spinal Cord Injury Individuals.

Robotic systems, such as Lokomat® have shown promising results in people with severe motor impairments, who suffered a stroke or other neurological damage. Robotic devices have also been used by people with more challenging damages, such as Spinal Cord Injury (SCI), using feedback strategies that provide information about the brain activity in real-time. This study proposes a novel Motor Imagery (MI)-based Electroencephalogram (EEG) Visual Neurofeedback (VNFB) system for Lokomat® to teach individuals how to modulate their own µ (8-12 Hz) and ß (15-20 Hz) rhythms during passive walking. Two individuals with complete SCI tested our VNFB system completing a total of 12 sessions, each on different days. For evaluation, clinical outcomes before and after the intervention and brain connectivity were analyzed. As findings, the sensitivity related to light touch and painful discrimination increased for both individuals. Furthermore, an improvement in neurogenic bladder and bowel functions was observed according to the American Spinal Injury Association Impairment Scale, Neurogenic Bladder Symptom Score, and Gastrointestinal Symptom Rating Scale. Moreover, brain connectivity between different EEG locations significantly ( [Formula: see text]) increased, mainly in the motor cortex. As other highlight, both SCI individuals enhanced their µ rhythm, suggesting motor learning. These results indicate that our gait training approach may have substantial clinical benefits in complete SCI individuals.

Multifunctional Hierarchical Nanoplatform with Anisotropic Bimodal Mesopores for Effective Neural Circuit Reconstruction after Spinal Cord Injury.

A persistent inflammatory response, intrinsic limitations in axonal regenerative capacity, and widespread presence of extrinsic axonal inhibitors impede the restoration of motor function after a spinal cord injury (SCI). A versatile treatment platform is urgently needed to address diverse clinical manifestations of SCI. Herein, we present a multifunctional nanoplatform with anisotropic bimodal mesopores for effective neural circuit reconstruction after SCI. The hierarchical nanoplatform features of a Janus structure consist of dual compartments of hydrophilic mesoporous silica (mSiO2) and hydrophobic periodic mesoporous organosilica (PMO), each possessing distinct pore sizes of 12 and 3 nm, respectively. Unlike traditional hierarchical mesoporous nanomaterials with dual-mesopores interlaced with each other, the two sets of mesopores in this Janus nanoplatform are spatially independent and possess completely distinct chemical properties. The Janus mesopores facilitate controllable codelivery of dual drugs with distinct properties: the hydrophilic macromolecular enoxaparin (ENO) and the hydrophobic small molecular paclitaxel (PTX). Anchoring with CeO2, the resulting mSiO2&PMO-CeO2-PTX&ENO nanoformulation not only effectively alleviates ROS-induced neuronal apoptosis but also enhances microtubule stability to promote intrinsic axonal regeneration and facilitates axonal extension by diminishing the inhibitory effect of extracellular chondroitin sulfate proteoglycans. We believe that this functional dual-mesoporous nanoplatform holds significant potential for combination therapy in treating severe multifaceted diseases.

Optimizing assessment of low frequency H-reflex depression in persons with spinal cord injury.

Considering the growing interest in clinical applications of neuromodulation, assessing effects of various modulatory approaches is increasingly important. Monosynaptic spinal reflexes undergo depression following repeated activation, offering a means to quantify neuromodulatory influences. Following spinal cord injury (SCI), changes in reflex modulation are associated with spasticity and impaired motor control. To assess disrupted reflex modulation, low-frequency depression (LFD) of Hoffman (H)-reflex excitability is examined, wherein the amplitudes of conditioned reflexes are compared to an unconditioned control reflex. Alternatively, some studies utilize paired-pulse depression (PPD) in place of the extended LFD train. While both protocols induce similar amounts of H-reflex depression in neurologically intact individuals, this may not be the case for persons with neuropathology. We compared the H-reflex depression elicited by PPD and by trains of 3-10 pulses to an 11-pulse LFD protocol in persons with incomplete SCI. The amount of depression produced by PPD was less than an 11-pulse train (mean difference = 0.137). When compared to the 11-pulse train, the 5-pulse train had a Pearson's correlation coefficient (R) of 0.905 and a coefficient of determination (R2) of 0.818. Therefore, a 5-pulse train for assessing LFD elicits modulation similar to the 11-pulse train and thus we recommend its use in lieu of longer trains.

The effects of music combined to paired associative stimulation on motor-evoked potentials and alertness in spinal cord injury patients and healthy subjects.

Paired associative stimulation (PAS) consisting of high-intensity transcranial magnetic stimulation (TMS) and high-frequency peripheral nerve stimulation (known as high-PAS) induces plastic changes and improves motor performance in patients with incomplete spinal cord injury (SCI). Listening to music during PAS may potentially improve mood and arousal and facilitate PAS-induced neuroplasticity via auditory-motor coupling, but the effects have not been explored. This pilot study aimed to determine if the effect of high-PAS on motor-evoked potentials (MEPs) and subjective alertness can be augmented with music. Ten healthy subjects and nine SCI patients received three high-PAS sessions in randomized order (PAS only, PAS with music synchronized to TMS, PAS with self-selected music). MEPs were measured before (PRE), after (POST), 30 min (POST30), and 60 min (POST60) after stimulation. Alertness was evaluated with a questionnaire. In healthy subjects, MEPs increased at POST in all sessions and remained higher at POST60 in PAS with synchronized music compared with the other sessions. There was no difference in alertness. In SCI patients, MEPs increased at POST and POST30 in PAS only but not in other sessions, whereas alertness was higher in PAS with self-selected music. More research is needed to determine the potential clinical effects of using music during high-PAS.

Potential Roles of Specific Subclasses of Premotor Interneurons in Spinal Cord Function Recovery after Traumatic Spinal Cord Injury in Adults.

The differential expression of transcription factors during embryonic development has been selected as the main feature to define the specific subclasses of spinal interneurons. However, recent studies based on single-cell RNA sequencing and transcriptomic experiments suggest that this approach might not be appropriate in the adult spinal cord, where interneurons show overlapping expression profiles, especially in the ventral region. This constitutes a major challenge for the identification and direct targeting of specific populations that could be involved in locomotor recovery after a traumatic spinal cord injury in adults. Current experimental therapies, including electrical stimulation, training, pharmacological treatments, or cell implantation, that have resulted in improvements in locomotor behavior rely on the modulation of the activity and connectivity of interneurons located in the surroundings of the lesion core for the formation of detour circuits. However, very few publications clarify the specific identity of these cells. In this work, we review the studies where premotor interneurons were able to create new intraspinal circuits after different kinds of traumatic spinal cord injury, highlighting the difficulties encountered by researchers, to classify these populations.

The Impact of Light Touch and Pin Prick on Functional Outcomes in Patients with Traumatic Spinal Cord Injury.

A spinal cord injury (SCI) can cause severe lifelong functional disability and profoundly affect an individual's daily life. We investigated the prediction of patients' post-SCI functional outcomes by evaluating sensory scores rather than motor scores, as the latter's association with functional outcomes is well established. We examined patients' responses to a light touch (LT) and pin prick (PP) at admission and the response data's usefulness as predictors of functional outcomes (i.e., ability to perform activities of daily living) at discharge. This exploratory observational study used data from the Japanese National Spinal Cord Injury Database (SCI-J). Data from 3,676 patients who met the inclusion criteria and were admitted for an SCI between 1997 and 2020 were analyzed. The motor score of the Functional Independence Measure (mFIM) at discharge was used as an index of functional outcome. A multiple regression analysis revealed that the mFIM was associated with both the LT response (ß=0.07 (0.01), p<0.001) and the PP response (ß=0.07 (0.01), p<0.001) at admission. The false discovery rate log-worth values for LT and PP were 6.6 and 8.5, respectively. Our findings demonstrate that LT and PP scores at admission can help predict patients' functional outcomes after an SCI, although the magnitude of their contributions is not high.

Efficacy of Walking Adaptability Training on Walking Capacity in Ambulatory People With Motor Incomplete Spinal Cord Injury: A Multicenter Pragmatic Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Balance and walking capacity are often impaired in people with motor incomplete spinal cord injury (iSCI), frequently resulting in reduced functional ambulation and participation. This study aimed to assess the efficacy of walking adaptability training compared to similarly dosed conventional locomotor and strength training for improving walking capacity, functional ambulation, balance confidence, and participation in ambulatory people with iSCI. METHODS: We conducted a 2-center, parallel-group, pragmatic randomized controlled trial. Forty-one people with iSCI were randomized to 6 weeks of (i) walking adaptability training (11 hours of Gait Real-time Analysis Interactive Lab (GRAIL) training-a treadmill in a virtual reality environment) or (ii) conventional locomotor and strength training (11 hours of treadmill training and lower-body strength exercises). The primary measure of walking capacity was maximal walking speed, measured with an overground 2-minute walk test. Secondary outcome measures included the Spinal Cord Injury Functional Ambulation Profile (SCI-FAP), the Activities-specific Balance Confidence (ABC) scale, and the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P). RESULTS: No significant difference in maximal walking speed between the walking adaptability (n = 17) and conventional locomotor and strength (n = 18) training groups was found 6 weeks after training at follow-up (-0.05 m/s; 95% CI = -0.12-0.03). In addition, no significant group differences in secondary outcomes were found. However, independent of intervention, significant improvements over time were found for maximal walking speed, SCI-FAP, ABC, and USER-P restrictions scores. Conclusions. Our findings suggest that walking adaptability training may not be superior to conventional locomotor and strength training for improving walking capacity, functional ambulation, balance confidence, or participation in ambulatory people with iSCI. TRIAL REGISTRATION: Dutch Trial Register; Effect of GRAIL training in iSCI.

Changes in intra- and interlimb reflexes from hindlimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats.

When the foot dorsum contacts an obstacle during locomotion, cutaneous afferents signal central circuits to coordinate muscle activity in the four limbs. Spinal cord injury disrupts these interactions, impairing balance and interlimb coordination. We evoked cutaneous reflexes by electrically stimulating left and right superficial peroneal nerves before and after two thoracic lateral hemisections placed on opposite sides of the cord at 9- to 13-week interval in seven adult cats (4 males and 3 females). We recorded reflex responses in ten hindlimb and five forelimb muscles bilaterally. After the first (right T5-T6) and second (left T10-T11) hemisections, coordination of the fore- and hindlimbs was altered and/or became less consistent. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-latency reflex responses in homonymous and crossed hindlimb muscles largely remained unaffected after staggered hemisections. However, mid- and long-latency homonymous and crossed responses in both hindlimbs occurred less frequently after staggered hemisections. In forelimb muscles, homolateral and diagonal mid- and long-latency response occurrence significantly decreased after the first and second hemisections. In all four limbs, however, when present, short-, mid- and long-latency responses maintained their phase-dependent modulation. We also observed reduced durations of short-latency inhibitory homonymous responses in left hindlimb extensors early after the first hemisection and delayed short-latency responses in the right ipsilesional hindlimb after the first hemisection. Therefore, changes in cutaneous reflex responses correlated with impaired balance/stability and interlimb coordination during locomotion after spinal cord injury. Restoring reflex transmission could be used as a biomarker to facilitate locomotor recovery. KEY POINTS: Cutaneous afferent inputs coordinate muscle activity in the four limbs during locomotion when the foot dorsum contacts an obstacle. Thoracic spinal cord injury disrupts communication between spinal locomotor centres located at cervical and lumbar levels, impairing balance and limb coordination. We investigated cutaneous reflexes during quadrupedal locomotion by electrically stimulating the superficial peroneal nerve bilaterally, before and after staggered lateral thoracic hemisections of the spinal cord in cats. We showed a loss/reduction of mid- and long-latency responses in all four limbs after staggered hemisections, which correlated with altered coordination of the fore- and hindlimbs and impaired balance. Targeting cutaneous reflex pathways projecting to the four limbs could help develop therapeutic approaches aimed at restoring transmission in ascending and descending spinal pathways.

Glutathione effect on functional and histological recovery after spinal cord injury in rats.

OBJECTIVE: The aim of this study was to evaluate the GSH effect on functional and histological recovery after experimental spinal cord injury in rats. METHODS: Forty Wistar rats were subjected to spinal cord injury through the Multicenter Animal Spinal Cord Injury Study (MASCIS) Impactor system. The rats were sorted and divided into four groups, as follows: Group 1 ‒ Laminectomy and spinal cord injury; Group 2 ‒ Laminectomy, spinal cord injury and Saline Solution (SS) 0.9%; Group 3 ‒ Laminectomy, spinal cord injury, and GSH; and Group 4 ‒ lLaminectomy without spinal cord injury. GSH and SS were administered intraperitoneally. Groups 1 and 4 received no intervention. RESULTS: The rats were evaluated for locomotor function recovery at seven different times by the Basso, Beattie, and Bresnahan (BBB) scale on days 2, 7, 14, 21, 28, 35, and 42 after the spinal cord injury. On day 42, the rats were sacrificed to analyze the histological findings of the injured spinal cord. In the group submitted to GSH, our experimental study revealed better functional scores on the BBB scale, horizontal ladder scale, and cranial and caudal axon count. The differences found were statistically significant in BBB scores and axonal count analysis. CONCLUSION: This study demonstrated that using glutathione in experimental spinal trauma can lead to better functional recovery and improved axonal regeneration rate in Wistar rats submitted to experimental spinal cord injury.

Inhibition of UHRF1 Improves Motor Function in Mice with Spinal Cord Injury.

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.

Treadmill training improves lung function and inhibits alveolar cell apoptosis in spinal cord injured rats.

Secondary lung injury after SCI is a major cause of patient mortality, with apoptosis playing a key role. This study aimed to explore the impact of treadmill training and miR145-5p on the MAPK/Erk signaling pathway and apoptosis in rats with complete SCI. SD rats were used to establish T10 segmental complete SCI models and underwent treadmill training 3, 7, or 14 days postinjury. Various techniques including arterial blood gas analysis, lung wet/dry weight ratio, HE staining, immunofluorescence staining, immunohistochemical staining, qRT-PCR, and Western blotting were employed to assess alterations in lung function and the expression levels of crucial apoptosis-related factors. In order to elucidate the specific mechanism, the impact of miR145-5p on the MAPK/Erk pathway and its role in apoptosis in lung cells were confirmed through miR145-5p overexpression and knockdown experiments. Following spinal cord injury (SCI), an increase in apoptosis, activation of the MAPK/Erk pathway, and impairment of lung function were observed in SCI rats. Conversely, treadmill training resulted in a reduction in alveolar cell apoptosis, suppression of the MAPK/Erk pathway, and enhancement of lung function. The gene MAP3K3 was identified as a target of miR145-5p. The influence of miR145-5p on the MAPK/Erk pathway and its impact on apoptosis in alveolar cells were confirmed through the manipulation of miR145-5p expression levels. The upregulation of miR145-5p in spinal cord injury (SCI) rats led to a reduction in MAP3K3 protein expression within lung tissues, thereby inhibiting the MAPK/Erk signaling pathway and decreasing apoptosis. Contrarily, rats with miR145-5p knockdown undergoing treadmill training exhibited an increase in miR145-5p expression levels, resulting in the inhibition of MAP3K3 protein expression in lung tissues, suppression of the MAPK/Erk pathway, and mitigation of lung cell apoptosis. Ultimately, the findings suggest that treadmill training may attenuate apoptosis in lung cells post-spinal cord injury by modulating the MAP3K3 protein through miR145-5p to regulate the MAPK/Erk signaling pathway.

Improvement in Motor and Walking Capacity during Multisegmental Transcutaneous Spinal Stimulation in Individuals with Incomplete Spinal Cord Injury.

Transcutaneous multisegmental spinal cord stimulation (tSCS) has shown superior efficacy in modulating spinal locomotor circuits compared to single-site stimulation in individuals with spinal cord injury (SCI). Building on these findings, we hypothesized that administering a single session of tSCS at multiple spinal segments may yield greater enhancements in muscle strength and gait function during stimulation compared to tSCS at only one or two segments. In our study, tSCS was applied at single segments (C5, L1, and Coc1), two segments (C5-L1, C5-Coc1, and L1-Coc1), or multisegments (C5-L1-Coc1) in a randomized order. We evaluated the 6-m walking test (6MWT) and maximum voluntary contraction (MVC) and assessed the Hmax/Mmax ratio during stimulation in ten individuals with incomplete motor SCI. Our findings indicate that multisegmental tSCS improved walking time and reduced spinal cord excitability, as measured by the Hmax/Mmax ratio, similar to some single or two-site tSCS interventions. However, only multisegmental tSCS resulted in increased tibialis anterior (TA) muscle strength. These results suggest that multisegmental tSCS holds promise for enhancing walking capacity, increasing muscle strength, and altering spinal cord excitability in individuals with incomplete SCI.

The effect of craniocervical flexion and neck endurance exercises plus pulmonary rehabilitation on pulmonary function in spinal cord injury: a pilot single-blinded randomised controlled trial.

STUDY DESIGN: Randomised controlled trial with computerised allocation, assessor blinding and intention-to-treat analysis. OBJECTIVE: This study wanted to prove that cervicocranial flexion exercise (CCFE) and superficial neck flexor endurance training combined with common pulmonary rehabilitation is feasible for improving spinal cord injury people's pulmonary function. SETTING: Taoyuan General Hospital, Ministry of Health and Welfare: Department of Physiotherapy, Taiwan. METHOD: Thirteen individuals who had sustained spinal cord injury for less than a year were recruited and randomised assigned into two groups. The experimental group was assigned CCFEs and neck flexor endurance training plus normal cardiopulmonary rehabilitation. The control group was assigned general neck stretching exercises plus cardiopulmonary rehabilitation. Lung function parameters such as forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow rate (PEFR), inspiratory capacity (IC), dyspnoea, pain, and neck stiffness were recorded once a week as short-term outcome measure. RESULT: The experimental group showed significant time effects for FVC (pre-therapy: 80.4 ± 21.4, post-therapy: 86.9 ± 16.9, p = 0.021, 95% CI: 0.00-0.26) and PEFR (pre-therapy: 67.0 ± 33.4; post-therapy: 78.4 ± 26.9, p = 0.042, 95% CI: 0.00-0.22) after the therapy course. Furthermore, the experimental group showed significant time effects for BDI (experimental group: 6.3 ± 3.0; control group: 10.8 ± 1.6, p = 0.012, 95% CI: 0.00-0.21). CONCLUSION: The exercise regime for the experimental group could efficiently increase lung function due to the following three reasons: first, respiratory accessory muscle endurance increases through training. Second, posture becomes less kyphosis resulting increasing lung volume. Third, the ratio between superficial and deep neck flexor is more synchronised. IRB TRIAL REGISTRATION: TYGH108045. CLINICAL TRIAL REGISTRATION: NCT04500223.