Traumatic Brain Injury and Traumatic Spinal Cord Injury.

OBJECTIVE: This article reviews the mechanisms of primary traumatic injury to the brain and spinal cord, with an emphasis on grading severity, identifying surgical indications, anticipating complications, and managing secondary injury. LATEST DEVELOPMENTS: Serum biomarkers have emerged for clinical decision making and prognosis after traumatic injury. Cortical spreading depolarization has been identified as a potentially modifiable mechanism of secondary injury after traumatic brain injury. Innovative methods to detect covert consciousness may inform prognosis and enrich future studies of coma recovery. The time-sensitive nature of spinal decompression is being elucidated. ESSENTIAL POINTS: Proven management strategies for patients with severe neurotrauma in the intensive care unit include surgical decompression when appropriate, the optimization of perfusion, and the anticipation and treatment of complications. Despite validated models, predicting outcomes after traumatic brain injury remains challenging, requiring prognostic humility and a model of shared decision making with surrogate decision makers to establish care goals. Penetrating injuries, especially gunshot wounds, are often devastating and require public health and policy approaches that target prevention.

Risk factors of video urodynamics and bladder management for long-term complications in patients with chronic spinal cord injury.

This study explores 15-year urological complications in chronic spinal cord injury (SCI) patients and investigates the predictive factors from video-urodynamic study (VUDS) and bladder management. Analyzing 864 SCI patients with a mean 15.6-year follow-up, we assessed complications and utilized multivariate logistic regression for risk evaluation. VUDS factors such as autonomic dysreflexia, detrusor sphincter dyssynergia, vesicourethral reflux (VUR), contracted bladder, and high voiding detrusor pressure significantly increased the likelihood of recurrent urinary tract infections (rUTI). Low bladder compliance, VUR, and contracted bladder notably raised the risk of hydronephrosis, while contracted bladder and detrusor overactivity with detrusor underactivity heightened chronic kidney disease risk. Volitional voiding reduced rUTI and VUR risk, whereas Valsalva maneuver-assisted voiding increased hydronephrosis risk. In conclusion, a contracted bladder identified in VUDS is associated with long-term urological complications in SCI, we propose that patients already experiencing a contracted bladder should prioritize volitional voiding as their preferred bladder management strategy to minimize the risk of additional complications such as rUTI and VUR. These findings unveil previously unexplored aspects in research, emphasizing the need for proactive management strategies in this patient population.

A Multimodal Assistive-Robotic-Arm Control System to Increase Independence After Tetraplegia.

Following tetraplegia, independence for completing essential daily tasks, such as opening doors and eating, significantly declines. Assistive robotic manipulators (ARMs) could restore independence, but typically input devices for these manipulators require functional use of the hands. We created and validated a hands-free multimodal input system for controlling an ARM in virtual reality using combinations of a gyroscope, eye-tracking, and heterologous surface electromyography (sEMG). These input modalities are mapped to ARM functions based on the user's preferences and to maximize the utility of their residual volitional capabilities following tetraplegia. The two participants in this study with tetraplegia preferred to use the control mapping with sEMG button functions and disliked winking commands. Non-disabled participants were more varied in their preferences and performance, further suggesting that customizability is an advantageous component of the control system. Replacing buttons from a traditional handheld controller with sEMG did not substantively reduce performance. The system provided adequate control to all participants to complete functional tasks in virtual reality such as opening door handles, turning stove dials, eating, and drinking, all of which enable independence and improved quality of life for these individuals.

Temporal dynamics of gait function in acute cervical spinal cord injury.

BACKGROUND: Following spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity. METHODS: This retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2-4 months, 4-6 months, and 6-8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau. RESULTS: In the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period. CONCLUSIONS: The plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group.

Prediction of gait recovery using machine learning algorithms in patients with spinal cord injury.

With advances in artificial intelligence, machine learning (ML) has been widely applied to predict functional outcomes in clinical medicine. However, there has been no attempt to predict walking ability after spinal cord injury (SCI) based on ML. In this situation, the main purpose of this study was to predict gait recovery after SCI at discharge from an acute rehabilitation facility using various ML algorithms. In addition, we explored important variables that were related to the prognosis. Finally, we attempted to suggest an ML-based decision support system (DSS) for predicting gait recovery after SCI. Data were collected retrospectively from patients with SCI admitted to an acute rehabilitation facility between June 2008 to December 2021. Linear regression analysis and ML algorithms (random forest [RF], decision tree [DT], and support vector machine) were used to predict the functional ambulation category at the time of discharge (FAC_DC) in patients with traumatic or non-traumatic SCI (n = 353). The independent variables were age, sex, duration of acute care and rehabilitation, comorbidities, neurological information entered into the International Standards for Neurological Classification of SCI worksheet, and somatosensory-evoked potentials at the time of admission to the acute rehabilitation facility. In addition, the importance of variables and DT-based DSS for FAC_DC was analyzed. As a result, RF and DT accurately predicted the FAC_DC measured by the root mean squared error. The root mean squared error of RF and the DT were 1.09 and 1.24 for all participants, 1.20 and 1.06 for those with trauma, and 1.12 and 1.03 for those with non-trauma, respectively. In the analysis of important variables, the initial FAC was found to be the most influential factor in all groups. In addition, we could provide a simple DSS based on strong predictors such as the initial FAC, American Spinal Injury Association Impairment Scale grades, and neurological level of injury. In conclusion, we provide that ML can accurately predict gait recovery after SCI for the first time. By focusing on important variables and DSS, we can guide early prognosis and establish personalized rehabilitation strategies in acute rehabilitation hospitals.

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.

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.

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.

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.

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.

Acute Hyperoxia Improves Spinal Cord Oxygenation and Circulatory Function Following Cervical Spinal Cord Injury in Rats.

Spinal cord injury is associated with spinal vascular disruptions that result in spinal ischemia and tissue hypoxia. This study evaluated the therapeutic efficacy of normobaric hyperoxia on spinal cord oxygenation and circulatory function at the acute stage of cervical spinal cord injury. Adult male Sprague Dawley rats underwent dorsal cervical laminectomy or cervical spinal cord contusion. At 1-2 days after spinal surgery, spinal cord oxygenation was monitored in anesthetized and spontaneously breathing rats through optical recording of oxygen sensor foils placed on the cervical spinal cord and pulse oximetry. The arterial blood pressure, heart rate, blood gases, and peripheral oxyhemoglobin saturation were also measured under hyperoxic (50% O2) and normoxic (21% O2) conditions. The results showed that contused animals had significantly lower spinal cord oxygenation levels than uninjured animals during normoxia. Peripheral oxyhemoglobin saturation, arterial oxygen partial pressure, and mean arterial blood pressure are significantly reduced following cervical spinal cord contusion. Notably, spinal oxygenation of contused rats could be improved to a level comparable to uninjured animals under hyperoxia. Furthermore, acute hyperoxia elevated blood pressure, arterial oxygen partial pressure, and peripheral oxyhemoglobin saturation. These results suggest that normobaric hyperoxia can significantly improve spinal cord oxygenation and circulatory function in the acute phase after cervical spinal cord injury. We propose that adjuvant normobaric hyperoxia combined with other hemodynamic optimization strategies may prevent secondary damage after spinal cord injury and improve functional recovery.

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 .

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.

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.

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.

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.

Alpha-tocopherol inhibits ferroptosis and promotes neural function recovery in rats with spinal cord injury via downregulating Alox15.

Spinal cord injury (SCI) is a type of central nervous system (CNS) injury in which ferroptosis is becoming a promising target for treatment. Alpha-tocopherol (Vitamin E, Vit E) is a compound with anti-ferroptosis activity. The mechanism of alpha-tocopherol in regulating ferroptosis after SCI has not been deeply studied. In this study, rats with SCI were treated by Alpha-tocopherol based on bioinformatic analysis and molecular docking prediction. Behavioral tests and histological findings showed that Alpha-tocopherol promoted neural function recovery and tissue repairment in rats with SCI. Subsequently, regulatory effects of Alpha-tocopherol on Alox15 and ferroptosis were detected and then localized by immunofluorescence. In vitro, alpha-tocopherol improved the ROS accumulation, iron overload, lipid peroxidation and mitochondrial dysfunction. The effects of Alpha-tocopherol on the expression of Alox15, Ptgs2 and 4Hne were validated in vitro. Finally, the inhibitory effects of Alpha-tocopherol on Alox15 and ferroptosis were weakened by the mutation of 87th residue of Alox15. In summary, alpha-tocopherol could alleviate SCI-induced ferroptosis by downregulating Alox15 to promote neural function recovery in rats with SCI. Findings in this study could help further our understanding on SCI-induced ferroptosis and provide a novel insight for treating SCI.

The effects of acteoside on locomotor recovery after spinal cord injury - The role of autophagy and apoptosis signaling pathway.

In the current study, we investigated the effects of acteoside as a phenylpropanoid glycoside on interaction with neurons to assesses locomotor recovery after spinal cord injury (SCI) in rats by focusing on evaluating the factors involved in autophagy, apoptosis, inflammation and oxidative stress processes. 49 Spargue-Dawley rats were prepared and divided into seven healthy and SCI groups receiving different concentrations of acteoside. After 28 days of disease induction and treatment with acteoside, a BBB score test was used to evaluate locomotor activity. Then, by preparing spinal cord cell homogenates, the expression levels of MAP1LC3A, MAP-2, glial fibrillary acidic protein (GFAP), Nrf2, Keap-1, Caspase 3 (Casp3), Bax, Bcl-2, TNF-a, IL-1B, reactive oxygen species (ROS), and malondialdehyde (MDA) were measured. Improvement of locomotor activity in SCI rats receiving acteoside was observed two weeks after the beginning of the experiment and continued until the fourth week. Both MAP1LC3A and MAP-2 were significantly up-regulated in SCI rats treated with acteoside compared to untreated SCI rats, and GFAP levels were significantly decreased in these animals. Pro-apoptotic proteins Bax and Casp3 and anti-apoptotic protein Bcl-2 were down-regulated and up-regulated, respectively, in SCI rats receiving acteoside. In addition, a significant downregulation of iNOS, TNF-α, and IL-1ß and a decrease in contents of both ROS and MDA as well as increases in Nrf2 and Keap-1 were seen in rats receiving acteoside. Furthermore, acteoside strongly interacted with MAP1LC3A, TNF-α, and Casp3 targets with binding affinities of -8.3 kcal/mol, -8.3 kcal/mol, and -8.5 kcal/mol, respectively, determined by molecular docking studies. In general, it can be concluded that acteoside has protective effects in SCI and can be considered as an adjuvant therapy in the treatment of this disease. However, more studies, especially clinical studies, are needed in this field.

Exposure to an enriched environment modulates the synaptic vesicle cycle in a mouse spinal cord injury model.

Spinal cord injury (SCI) leads to motor and sensory impairment below the site of injury, thereby necessitating rehabilitation. An enriched environment (EE) increases social interaction and locomotor activity in a mouse model, similar to human rehabilitation. However, the impact of EE on presynaptic plasticity in gene expression levels remains unclear. Hence, this study aimed to investigate the therapeutic potential of EE in an SCI mouse model. Mice with spinal cord contusion were divided into two groups: those housed in standard cages (control) and those in EE conditions (EE). Each group was housed separately for either 2- or 8-weeks post-injury, after which RNA sequencing was performed and compared to a sham group (receiving only a dorsal laminectomy). The synaptic vesicle cycle (SVC) pathway and related genes showed significant downregulation after SCI at both time points. Subsequently, we investigated whether exposure to EE for 2- and 8-weeks post-SCI could modulate the SVC pathway and its related genes. Notably, exposure to EE for 8 weeks resulted in a marked reversal effect of SVC-related gene expression, along with stimulation of axon regeneration and mitigation of locomotor activity loss. Thus, prolonged exposure to EE increased presynaptic activity, fostering axon regeneration and functional improvement by modulating the SVC in the SCI mouse model. These findings suggest that EE exposure proves effective in inducing activity-dependent plasticity, offering a promising therapeutic approach akin to rehabilitation training in patients with SCI.

Forelimb movements contribute to hindlimb cutaneous reflexes during locomotion in cats.

During quadrupedal locomotion, interactions between spinal and supraspinal circuits and somatosensory feedback coordinate forelimb and hindlimb movements. How this is achieved is not clear. To determine whether forelimb movements modulate hindlimb cutaneous reflexes involved in responding to an external perturbation, we stimulated the superficial peroneal nerve in six intact cats during quadrupedal locomotion and during hindlimb-only locomotion (with forelimbs standing on stationary platform) and in two cats with a low spinal transection (T12-T13) during hindlimb-only locomotion. We compared cutaneous reflexes evoked in six ipsilateral and four contralateral hindlimb muscles. Results showed similar occurrence and phase-dependent modulation of short-latency inhibitory and excitatory responses during quadrupedal and hindlimb-only locomotion in intact cats. However, the depth of modulation was reduced in the ipsilateral semitendinosus during hindlimb-only locomotion. Additionally, longer-latency responses occurred less frequently in extensor muscles bilaterally during hindlimb-only locomotion, whereas short-latency inhibitory and longer-latency excitatory responses occurred more frequently in the ipsilateral and contralateral sartorius anterior, respectively. After spinal transection, short-latency inhibitory and excitatory responses were similar to both intact conditions, whereas mid- or longer-latency excitatory responses were reduced or abolished. Our results in intact cats and the comparison with spinal-transected cats suggest that the absence of forelimb movements suppresses inputs from supraspinal structures and/or cervical cord that normally contribute to longer-latency reflex responses in hindlimb extensor muscles.NEW & NOTEWORTHY During quadrupedal locomotion, the coordination of forelimb and hindlimb movements involves central circuits and somatosensory feedback. To demonstrate how forelimb movement affects hindlimb cutaneous reflexes during locomotion, we stimulated the superficial peroneal nerve in intact cats during quadrupedal and hindlimb-only locomotion as well as in spinal-transected cats during hindlimb-only locomotion. We show that forelimb movement influences the modulation of hindlimb cutaneous reflexes, particularly the occurrence of long-latency reflex responses.