Sitting Pressure Measurements in Wheelchair Users-Can the Effects of Daily Relief Activities Be Depicted?

Seat pressure measurements in wheelchair users have been available for some time; however, repeated measurements from a commercially available pressure mat over 90 min did not differ in the pressure-loaded measurement area or the coordinates of the center of pressure, even in participants who were able to reposition themselves in the wheelchair. The question therefore arises: to what extent are there other parameters that reflect the activity of wheelchair users with the pressure mat? To investigate this, a commercial pressure mat (BodiTrak®) was used to perform the measurements of pressure of 33 adult wheelchair-dependent people with spinal cord injury after 30 and 90 min sitting on the cushion. In addition to the standard output of the pressure mat, graph-based surface analyses (calculation of the area of maximum pressure, calculation of the pressure-loaded measurement area, and pressure-area ratio) was performed retrospectively using Python 3.7. The analysis of the measurements after 30 and 90 min was performed by distinguishing the participants between those who could actively change their position (N = 24) and those who could not (N = 9). The parameters of the pressure mat and the graph-based analyses remained unchanged for active participants. In participants who were unable to actively change their position, the area of maximum pressure and the pressure-area ratio (ratio of maximum pressure area and total pressure-loaded area) increased. Significant differences between minutes 30 and 90 are only found for the pressure-area ratio. Thus, when measuring the seat pressure of wheelchair users, the pressure-area ratio should be taken into account as it reflects the daily relief activities of wheelchair users.

Anatomical Registration of Implanted Sensors Improves Accuracy of Trunk Tilt Estimates with a Networked Neuroprosthesis.

For individuals with spinal cord injuries (SCIs) above the midthoracic level, a common complication is the partial or complete loss of trunk stability in the seated position. Functional neuromuscular stimulation (FNS) can restore seated posture and other motor functions after paralysis by applying small electrical currents to the peripheral motor nerves. In particular, the Networked Neuroprosthesis (NNP) is a fully implanted, modular FNS system that is also capable of capturing information from embedded accelerometers for measuring trunk tilt for feedback control of stimulation. The NNP modules containing the accelerometers are located in the body based on surgical constraints. As such, their exact orientations are generally unknown and cannot be easily assessed. In this study, a method for estimating trunk tilt that employed the Gram-Schmidt method to reorient acceleration signals to the anatomical axes of the body was developed and deployed in individuals with SCI using the implanted NNP system. An anatomically realistic model of a human trunk and five accelerometer sensors was developed to verify the accuracy of the reorientation algorithm. Correlation coefficients and root mean square errors (RMSEs) were calculated to compare target trunk tilt estimates and tilt estimates derived from simulated accelerometer signals under a variety of conditions. Simulated trunk tilt estimates with correlation coefficients above 0.92 and RMSEs below 5° were achieved. The algorithm was then applied to accelerometer signals from implanted sensors installed in three NNP recipients. Error analysis was performed by comparing the correlation coefficients and RMSEs derived from trunk tilt estimates calculated from implanted sensor signals to those calculated via motion capture data, which served as the gold standard. NNP-derived trunk tilt estimates exhibited correlation coefficients between 0.80 and 0.95 and RMSEs below 13° for both pitch and roll in most cases. These findings suggest that the algorithm is effective at estimating trunk tilt with the implanted sensors of the NNP system, which implies that the method may be appropriate for extracting feedback signals for control systems for seated stability with NNP technology for individuals who have reduced control of their trunk due to paralysis.

Research progress of microRNA in spinal cord injury.

Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.

Pyroptosis in Spinal Cord Injury: Implications for Pathogenesis and Therapeutic Approaches.

Traumatic spinal cord injury (SCI) is a serious disease of the central nervous system. Aside from the limited intrinsic regenerative capacity of neurons, complex microenvironmental disturbances can also lead to further cellular damage and growth inhibition. Programmed cell death regulated by pyroptosis has an important role in the pathogenesis of SCI. While there has been a wealth of new knowledge regarding cellular pyroptosis, a detailed understanding of its role in SCI and possible therapeutic strategies is still lacking. This review summarizes current advances in the regulatory role of pyroptosis-regulated cell death and inflammasome components in the inhibitory microenvironment following SCI, as well as recent therapeutic advances.

Peripheral nerve transfers for dysfunctions in central nervous system injuries: a systematic review.

BACKGROUND: The review highlights recent advancements and innovative uses of nerve transfer surgery in treating dysfunctions caused by central nervous system (CNS) injuries, with a particular focus on spinal cord injury (SCI), stroke, traumatic brain injury, and cerebral palsy. METHODS: A comprehensive literature search was conducted regarding nerve transfer for restoring sensorimotor functions and bladder control following injuries of spinal cord and brain, across PubMed and Web of Science from January 1920 to May 2023. Two independent reviewers undertook article selection, data extraction, and risk of bias assessment with several appraisal tools, including the Cochrane Risk of Bias Tool, the JBI Critical Appraisal Checklist, and SYRCLE's ROB tool. The study protocol has been registered and reported following PRISMA and AMSTAR guidelines. RESULTS: Nine hundred six articles were retrieved, of which 35 studies were included (20 on SCI and 15 on brain injury), with 371 participants included in the surgery group and 192 in the control group. These articles were mostly low-risk, with methodological concerns in study types, highlighting the complexity and diversity. For SCI, the strength of target muscle increased by 3.13 of Medical Research Council grade, and the residual urine volume reduced by more than 100 ml in 15 of 20 patients. For unilateral brain injury, the Fugl-Myer motor assessment (FMA) improved 15.14-26 score in upper extremity compared to 2.35-26 in the control group. The overall reduction in Modified Ashworth score was 0.76-2 compared to 0-1 in the control group. Range of motion (ROM) increased 18.4-80° in elbow, 20.4-110° in wrist and 18.8-130° in forearm, while ROM changed -4.03°-20° in elbow, -2.08°-10° in wrist, -2.26°-20° in forearm in the control group. The improvement of FMA in lower extremity was 9 score compared to the presurgery. CONCLUSION: Nerve transfer generally improves sensorimotor functions in paralyzed limbs and bladder control following CNS injury. The technique effectively creates a 'bypass' for signals and facilitates functional recovery by leveraging neural plasticity. It suggested a future of surgery, neurorehabilitation and robotic-assistants converge to improve outcomes for CNS.

DTI-MRI at 2 days after spinal cord injury accurately predicts long-term locomotor function recovery in rats.

OBJECTIVE: Spinal cord injury (SCI) damages an individual's sensory, motor, and autonomic functions and represents a social emergency, mostly in developed countries. Accurate and timely diagnosis of the severity of SCI must be carried out as quickly as possible to allow time for drug and therapy testing in the early stages after injury. MATERIALS AND METHODS: Male Dark Agouti (DA) rats underwent spinal cord cryoinjury at the T13 level of the spine. Under typical conditions, in vivo magnetic resonance imaging (MRI) T2 and echo-planar imaging - diffusion tensor imaging (EPI-DTI) examinations were conducted. This involved the reconstruction of nerve tracts and the measurement of the fractional anisotropy (FA) index, as well as measurements of the ratio of Hyper/Hypo intensive areas and spinal cord injury severity scores. RESULTS: Our study shows that, after cryoinjury, the FA significantly decreased in all animals. An increase in FA level, derived from EPI-DTI within 2 days after SCI, accurately predicts long-term locomotor function recovery. In rats with higher FA, recorded on day 2 after injury, complete restoration of locomotor function was observed, while at low FA values, the animals maintained stable monoplegia. CONCLUSIONS: Our results, though validating the T2 10-grade MRI scale for SCI, indicate that FA would represent the MRI technical instrument, which would better monitor the evolution of SCI and, accordingly, better objectively evaluate the impact of potentially therapeutic protocols for spinal cord traumatic injury. Despite the results achieved, significant difficulties must be overcome on the way to successful clinical implementation of the findings in humans.

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.

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.

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.

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.

Bimanual coordination and spinal cord neuromodulation: how neural substrates of bimanual movements are altered by transcutaneous spinal cord stimulation.

Humans use their arms in complex ways that often demand two-handed coordination. Neurological conditions limit this impressive feature of the human motor system. Understanding how neuromodulatory techniques may alter neural mechanisms of bimanual coordination is a vital step towards designing efficient rehabilitation interventions. By non-invasively activating the spinal cord, transcutaneous spinal cord stimulation (tSCS) promotes recovery of motor function after spinal cord injury. A multitude of research studies have attempted to capture the underlying neural mechanisms of these effects using a variety of electrophysiological tools, but the influence of tSCS on cortical rhythms recorded via electroencephalography remains poorly understood, especially during bimanual actions. We recruited 12 neurologically intact participants to investigate the effect of cervical tSCS on sensorimotor cortical oscillations. We examined changes in the movement kinematics during the application of tSCS as well as the cortical activation level and interhemispheric connectivity during the execution of unimanual and bimanual arm reaching movements that represent activities of daily life. Behavioral assessment of the movements showed improvement of movement time and error during a bimanual common-goal movement when tSCS was delivered, but no difference was found in the performance of unimanual and bimanual dual-goal movements with the application of tSCS. In the alpha band, spectral power was modulated with tSCS in the direction of synchronization in the primary motor cortex during unimanual and bimanual dual-goal movements and in the somatosensory cortex during unimanual movements. In the beta band, tSCS significantly increased spectral power in the primary motor and somatosensory cortices during the performance of bimanual common-goal and unimanual movements. A significant increase in interhemispheric connectivity in the primary motor cortex in the alpha band was only observed during unimanual tasks in the presence of tSCS. Our observations provide, for the first time, information regarding the supra-spinal effects of tSCS as a neuromodulatory technique applied to the spinal cord during the execution of bi- and unimanual arm movements. They also corroborate the suppressive effect of tSCS at the cortical level reported in previous studies. These findings may guide the design of improved rehabilitation interventions using tSCS for the recovery of upper-limb function in the future.

Diurnal variation of heart rate variability in individuals with spinal cord injury.

BACKGROUND: Heart rate variability (HRV) may provide objective information about cardiogenic autonomic balance in individuals with spinal cord injury (SCI). The aim of this study was to characterize the diurnal variation of HRV in individuals with SCI at lesion level T6 and above and lesion level below T6. METHODS: This was a retrospective analysis of a prior cross-sectional study. Individuals with chronic SCI underwent 24 h recording of the time between consecutive R waves (RR interval) to derive parameters of HRV as follows: standard deviation of all normal-to-normal R-R intervals (SDNN) and square root of the mean of the squared differences between successive R-R intervals (RMSSD) (time domain); and high frequency power (HF), low-frequency power (LF), very low frequency power (VLF), ultra-low frequency power (ULF) and total power (TP) (frequency domain). Changes in the magnitude of HRV outcomes over the 24 h period were investigated using a novel multi-component cosinor model constrained to the form of a three-harmonic Fourier series. RESULTS: Participants were grouped as lesion level T6 and above (n = 22) or below T6 (n = 36). Most of them were male (n = 40, 69%) and the median age (interquartile range) was 50.5 (28) years. Both groups exhibited similar diurnal patterns in most HRV metrics. The lowest values occurred in the late afternoon (4-6 pm) and gradually increased, peaking around midnight to early morning (1-6 am). Exceptions included RMSSD, which peaked before midnight, and ULF, which showed a double peak pattern that peaked from 11 am to 1 pm and 4-6 am in participants with lesion level at T6 and above. The HRV values in participants with lesion level T6 and above were generally lower than participants with lesion level below T6, except for peak values of RMSSD, HF and LF. CONCLUSION: This study demonstrated substantial diurnal variation of HRV in participants with SCI in both groups of participants. In clinical and research settings, diurnal variations in HRV must be taken into consideration.

Correlation of bilateral M1 hand area excitability and overall functional recovery after spinal cord injury: protocol for a prospective cohort study.

BACKGROUND: After spinal cord injury (SCI), a large number of survivors suffer from severe motor dysfunction (MD). Although the injury site is in the spinal cord, excitability significantly decreases in the primary motor cortex (M1), especially in the lower extremity (LE) area. Unfortunately, M1 LE area-targeted repetitive transcranial magnetic stimulation (rTMS) has not achieved significant motor improvement in individuals with SCI. A recent study reported that the M1 hand area in individuals with SCl contains a compositional code (the movement-coding component of neural activity) that links matching movements from the upper extremities (UE) and the LE. However, the correlation between bilateral M1 hand area excitability and overall functional recovery is unknown. OBJECTIVE: To clarify the changes in the excitability of the bilateral M1 hand area after SCI and its correlation with motor recovery, we aim to specify the therapeutic parameters of rTMS for SCI motor rehabilitation. METHODS: This study is a 12-month prospective cohort study. The neurophysiological and overall functional status of the participants will be assessed. The primary outcomes included single-pulse and paired-pulse TMS. The second outcome included functional near-infrared spectroscopy (fNIRS) measurements. Overall functional status included total motor score, modified Ashworth scale score, ASIA Impairment Scale grade, spinal cord independence measure and modified Barthel index. The data will be recorded for individuals with SCI at disease durations of 1 month, 2 months, 4 months, 6 months and 12 months. The matched healthy controls will be measured during the same period of time after recruitment. DISCUSSION: The present study is the first to analyze the role of bilateral M1 hand area excitability changes in the evaluation and prediction of overall functional recovery (including motor function and activities of daily living) after SCI, which will further expand the traditional theory of the predominant role of M1, optimize the current rTMS treatment, and explore the brain-computer interface design for individuals with SCI. TRIAL REGISTRATION NUMBER: ChiCTR2300068831.

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.

Patterns of neurogenic lower urinary tract dysfunction management and associated factors among Chinese community-dwelling individuals with spinal cord injury.

To identify different patterns of neurogenic lower urinary tract dysfunction management among Chinese community-dwelling individuals with spinal cord injury and explore the factors associated with latent classes. This was a cross-sectional study conducted in communities throughout China Mainland. Participants were recruited through the China Association of Persons with Physical Disability and a total of 2582 participants was included in the analysis. The data were collected by a questionnaire consisting of socio-demographic factors, disease-related factors, and a list of 8 bladder management methods. Latent class analysis was used to identify different latent classes of neurogenic lower urinary tract dysfunction management. Then the multinomial logistic regression was applied to analyze the relationship between neurogenic lower urinary tract dysfunction management patterns and socio-demographic and disease-related factors. Neurogenic lower urinary tract dysfunction management pattern among community-dwelling individuals with spinal cord injury was divided into four latent classes: "urinal collecting apparatus dominated pattern" (40.3%), "bladder compression dominated pattern" (30.7%), "intermittent catheterization dominated pattern" (19.3%) and "urethral indwelling catheterization dominated pattern" (9.6%). Multinomial logistic regression analysis found that the employment status, residential region, nursing need, payment method for catheterization products, hand function, time since spinal cord injury, urinary incontinence and concerns about social interaction affected by urination problems were significantly associated with latent classes. Only 19.3% of people used the intermittent catheterization as their main neurogenic lower urinary tract dysfunction management method. More attention needs to be paid to the promotion of the standardization process of intermittent catheterization in community-dwelling individuals with spinal cord injury. The associated factors of the four classes can be used for tailored and targeted interventions to increase the use of intermittent catheterization.

Validation of basal metabolic rate equations in persons with innervated and denervated chronic spinal cord injury.

Basal metabolic rate (BMR) measurement is time consuming and requires specialized equipment. Prediction equations allow clinicians and researchers to estimate BMR; however, their accuracy may vary across individuals with chronic spinal cord injury (SCI). The objective of this study was to investigate the validity of SCI-specific equations as well as able-bodied (AB) prediction equations in individuals with upper motor neuron (UMN), lower motor neuron (LMN), and females with SCI. Twenty-six men and women with chronic SCI (n = 12 innervated males, n = 6 innervated females, n = 8 denervated males) participated in this cross-sectional study. BMR values were measured by indirect calorimetry. Body composition (dual-energy X-ray absorptiometry and anthropometrics) assessment was conducted. AB-prediction equations [Cunningham, Nelson, Owen, Harris and Benedict, Mifflin, Schofield, Henry] and SCI-specific equations [Chun and Nightingale & Gorgey] were used to estimate and validate BMR. The accuracy of AB-specific FFM equations in predicting BMR was evaluated using Bland-Altman plots, paired t-tests, and error metrics. Measured BMR for innervated males, females, and denervated males was 1436 ± 213 kcal/day, 1290 ± 114, and 1597 ± 333 kcal/day, respectively. SCI-specific equations by Chun et al., Nightingale & Gorgey, and AB-specific FFM equations accurately predicted BMR for innervated males. For the denervated males, Model 4 equation by Nightingale & Gorgey was not different (p = 0.18), and Bland-Altman analyses showed negative mean bias but similar limits of agreement between measured and predicted BMR for the SCI-specific equations and AB-specific FFM equations. We demonstrated that SCI-specific equations accurately predicted BMR for innervated males but underpredicted it for denervated males. The Model 4 equation by Nightingale & Gorgey accurately estimated BMR in females with SCI. Findings from the current study will help to determine caloric needs in different sub-groups of SCI.

Microglia promote maladaptive plasticity in autonomic circuitry after spinal cord injury in mice.

Robust structural remodeling and synaptic plasticity occurs within spinal autonomic circuitry after severe high-level spinal cord injury (SCI). As a result, normally innocuous visceral or somatic stimuli elicit uncontrolled activation of spinal sympathetic reflexes that contribute to systemic disease and organ-specific pathology. How hyperexcitable sympathetic circuitry forms is unknown, but local cues from neighboring glia likely help mold these maladaptive neuronal networks. Here, we used a mouse model of SCI to show that microglia surrounded active glutamatergic interneurons and subsequently coordinated multi-segmental excitatory synaptogenesis and expansion of sympathetic networks that control immune, neuroendocrine, and cardiovascular functions. Depleting microglia during critical periods of circuit remodeling after SCI prevented maladaptive synaptic and structural plasticity in autonomic networks, decreased the frequency and severity of autonomic dysreflexia, and prevented SCI-induced immunosuppression. Forced turnover of microglia in microglia-depleted mice restored structural and functional indices of pathological dysautonomia, providing further evidence that microglia are key effectors of autonomic plasticity. Additional data show that microglia-dependent autonomic plasticity required expression of triggering receptor expressed on myeloid cells 2 (Trem2) and α2δ-1-dependent synaptogenesis. These data suggest that microglia are primary effectors of autonomic neuroplasticity and dysautonomia after SCI in mice. Manipulating microglia may be a strategy to limit autonomic complications after SCI or other forms of neurologic disease.

Recent advances on signaling pathways and their inhibitors in spinal cord injury.

Spinal cord injury (SCI) is a serious and disabling central nervous system injury. Its complex pathological mechanism can lead to sensory and motor dysfunction. It has been reported that signaling pathway plays a key role in the pathological process and neuronal recovery mechanism of SCI. Such as PI3K/Akt, MAPK, NF-κB, and Wnt/ß-catenin signaling pathways. According to reports, various stimuli and cytokines activate these signaling pathways related to SCI pathology, thereby participating in the regulation of pathological processes such as inflammation response, cell apoptosis, oxidative stress, and glial scar formation after injury. Activation or inhibition of relevant pathways can delay inflammatory response, reduce neuronal apoptosis, prevent glial scar formation, improve the microenvironment after SCI, and promote neural function recovery. Based on the role of signaling pathways in SCI, they may be potential targets for the treatment of SCI. Therefore, understanding the signaling pathway and its inhibitors may be beneficial to the development of SCI therapeutic targets and new drugs. This paper mainly summarizes the pathophysiological process of SCI, the signaling pathways involved in SCI pathogenesis, and the potential role of specific inhibitors/activators in its treatment. In addition, this review also discusses the deficiencies and defects of signaling pathways in SCI research. It is hoped that this study can provide reference for future research on signaling pathways in the pathogenesis of SCI and provide theoretical basis for SCI biotherapy.

PTEN inhibition promotes robust growth of bulbospinal respiratory axons and partial recovery of diaphragm function in a chronic model of cervical contusion spinal cord injury.

High spinal cord injury (SCI) leads to persistent and debilitating compromise in respiratory function. Cervical SCI not only causes the death of phrenic motor neurons (PhMNs) that innervate the diaphragm, but also damages descending respiratory pathways originating in the rostral ventral respiratory group (rVRG) located in the brainstem, resulting in denervation and consequent silencing of spared PhMNs located caudal to injury. It is imperative to determine whether interventions targeting rVRG axon growth and respiratory neural circuit reconnection are efficacious in chronic cervical contusion SCI, given that the vast majority of individuals are chronically-injured and most cases of SCI involve contusion-type damage to the cervical region. We therefore employed a rat model of chronic cervical hemicontusion to test therapeutic manipulations aimed at reconstructing damaged rVRG-PhMN-diaphragm circuitry to achieve recovery of respiratory function. At a chronic time point post-injury, we systemically administered: an antagonist peptide directed against phosphatase and tensin homolog (PTEN), a central inhibitor of neuron-intrinsic axon growth potential; an antagonist peptide directed against receptor-type protein tyrosine phosphatase sigma (PTPσ), another important negative regulator of axon growth capacity; or a combination of these two peptides. PTEN antagonist peptide (PAP4) promoted partial recovery of diaphragm motor activity out to nine months post-injury (though this effect depended on the anesthetic regimen used during recording), while PTPσ peptide did not impact diaphragm function after cervical SCI. Furthermore, PAP4 promoted robust growth of descending bulbospinal rVRG axons caudal to the injury within the denervated portion of the PhMN pool, while PTPσ peptide did not affect rVRG axon growth at this location that is critical to control of diaphragmatic respiratory function. In conclusion, we find that, when PTEN inhibition is targeted at a chronic time point following cervical contusion, our non-invasive PAP4 strategy can successfully promote significant regrowth of damaged respiratory neural circuitry and also partial recovery of diaphragm motor function.

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.