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Background The gut microbiome is a diverse network of bacteria which inhabit our digestive tract and is crucial for efficient cellular metabolism, nutrient absorption, and immune system development. Spinal cord injury (SCI) disrupts autonomic function below the level of injury and can alter the composition of the gut microbiome. Studies in rodent models have shown that SCI-induced bacterial imbalances in the gut can exacerbate the spinal cord damage and impair recovery. In this study we, for the first time, characterized the composition of the gut microbiome in a Yucatan minipig SCI model. We compared the relative abundance of the most dominant bacterial phyla in control samples to those collected from animals who underwent a contusion-compression SCI at the 2nd or 10th Thoracic level. Results We identify specific bacterial fluctuations that are unique to SCI animals, which were not found in uninjured animals given the same dietary regimen or antibiotic administration. Further, we identified a specific time-frame, “SCI-acute stage”, during which many of these bacterial fluctuations occur before returning to “baseline” levels. Conclusion This work presents a dynamic view of the microbiome changes that accompany SCI, establishes a resource for future studies and to understand the changes that occur to gut microbiota after spinal cord injury and may point to a potential therapeutic target for future treatment.

Spinal cord injury (SCI) impairs the cardiovascular responses to postural challenge, leading to the development of orthostatic hypotension (OH). Here, we apply lower body negative pressure (LBNP) to rodents with high-level SCI to demonstrate the usefulness of LBNP as a model for experimental OH studies, and to explore the effect of simulated OH on cardiovascular and cerebrovascular function following SCI. Male Wistar rats (

In this paper, we investigate the forelimbs somatosensory evoked potential (SSEP) signals, which are representative of the integrity of ascending sensory pathways and their stability as well as function, recorded from corresponding cortices, post thoracic spinal cord injury (SCI). We designed a series of distinctive transection SCI to investigate whether forelimbs SSEPs change after right T10 hemi-transection, T8 and T10 double hemi-transection and T8 complete transection in rat model of SCI. We used electrical stimuli to stimulate median nerves and recorded SSEPs from left and right somatosensory areas of both cortices. We monitored pre-injury baseline and verified changes in forelimbs SSEP signals on Days 4, 7, 14, and 21 post-injury. We previously characterized hindlimb SSEP changes for the abovementioned transection injuries. The focus of this article is to investigate the quality and quantity of changes that may occur in the forelimb somatosensory pathways post-thoracic transection SCI. It is important to test the stability of forelimb SSEPs following thoracic SCI because of their potential utility as a proxy baseline for the traumatic SCIs in clinical cases wherein there is no opportunity to gather baseline of the lower extremities. We observed that the forelimb SSEP amplitudes increased following thoracic SCI but gradually returned to the baseline. Despite changes found in the raw signals, statistical analysis found forelimb SSEP signals become stable relatively soon. In summary, though there are changes in value (with p > 0.05), they are not statistically significant. Therefore, the null hypothesis that the mean of the forelimb SSEP signals are the same across multiple days after injury onset cannot be rejected during the acute phase.

OBJECTIVE The aim of this study was to evaluate whether the investigational Neuro-Spinal Scaffold (NSS), a highly porous bioresorbable polymer device, demonstrates probable benefit for safety and neurological recovery in patients with complete (AIS grade A) T2–12 spinal cord injury (SCI) when implanted ≤ 96 hours postinjury. METHODS This was a prospective, open-label, multicenter, single-arm study in patients with a visible contusion on MRI. The NSS was implanted into the epicenter of the postirrigation intramedullary spinal cord contusion cavity with the intention of providing structural support to the injured spinal cord parenchyma. The primary efficacy endpoint was the proportion of patients who had an improvement of ≥ 1 AIS grade (i.e., conversion from complete paraplegia to incomplete paraplegia) at the 6-month follow-up visit. A preset objective performance criterion established for the study was defined as an AIS grade conversion rate of ≥ 25%. Secondary endpoints included change in neurological level of injury (NLI). This analysis reports on data through 6-month follow-up assessments. RESULTS Nineteen patients underwent NSS implantation. There were 3 early withdrawals due to death, which were all determined by investigators to be unrelated to the NSS or the implantation procedure. Seven of 16 patients (43.8%) who completed the 6-month follow-up visit had conversion of neurological status (AIS grade A to grade B [n = 5] or C [n = 2]). Five patients showed improvement in NLI of 1 to 2 levels compared with preimplantation assessment, 3 patients showed no change, and 8 patients showed deterioration of 1 to 4 levels. There were no unanticipated or serious adverse device effects or serious adverse events related to the NSS or the implantation procedure as determined by investigators. CONCLUSIONS In this first-in-human study, implantation of the NSS within the spinal cord appeared to be safe in the setting of surgical decompression and stabilization for complete (AIS grade A) thoracic SCI. It was associated with a 6-month AIS grade conversion rate that exceeded historical controls. The INSPIRE study data demonstrate that the potential benefits of the NSS outweigh the risks in this patient population and support further clinical investigation in a randomized controlled trial. Clinical trial registration no.: NCT02138110 (clinicaltrials.gov)

The results of kinesiotherapy treatment in patients after incomplete spinal cord injury (iSCI) are inconclusive, mostly due to different, subjective evaluation methods. The study aims to evaluate the range of functional regeneration in long-term 13 months follow-up using comparative neurophysiological tests after uniform kinesiotherapy in patients with thoracic iSCI.Comparative tests were performed of sensory perception in dermatomes Th1-S1, electromyography (at rest-rEMG and during maximal contraction-mcEMG) in the muscles of the trunk and lower extremities, electroneurography (ENG) of the motor fibres of the lower extremities, and motor-evoked potential induced transcranially (MEP) before and after treatment in 25 iSCI patients. All subjects were treated with the same kinesiotherapeutic procedures.A moderate increase was found in amplitudes in rEMG and mcEMG recordings fromthe rectus abdominis and rectus femoris muscles, MEPs amplitudes, and amplitudes after peroneal nerve stimulations in ENG studies. There was no improvement in sensory perception.Following the proposed kinesiotherapy algorithm, patients after thoracic iSCI presented a moderate more motor than sensory functions improvement. Applied neurorehabilitation evoked normalization of muscle tension, moderate improvement of rectus abdominis and rectus femoris muscles motor units activity, and motor central and peripheral neural impulses transmission. The comparative neurophysiological assessment provide a more precise and objective insight into the functional status of afferent and efferent systems than the classical clinical approach in iSCI patients.

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Activitat física; Lesió medul·lar Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Actividad física; Lesión de la médula espinal Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Physical activity; Spinal cord injury Context The emergence of COVID-19 caused a new public health crisis, leading to major changes in daily life routines, often including physical activity (PA) levels. The main goal of this study was to analyze the differences in self-reported physical activity of people with complete spinal cord injuries between the time prior to the COVID-19 lockdown and the lockdown period itself. Methods A sample of 20 participants with complete thoracic spinal cord injuries completed the Physical Activity Scale for Individuals with Physical Disabilities before and during the COVID-19 lockdown. Results The results showed differences between the pre-lockdown and lockdown measurements in total self-reported PA (z=−3.92; P

Gut microbiota are the candidate biomarkers for neurogenic bowel dysfunction (NBD) in patients with spinal cord injury (SCI). We aimed to identify the common features between patients with varying degree of thoracic SCI and healthy individuals and subpopulations of microbiota correlated with the serum biomarkers. Twenty-one patients with complete thoracic SCI (CTSCI), 24 with incomplete thoracic SCI (ITSCI), and 24 healthy individuals (HC) were enrolled in this study. Fresh stool samples and clinical data were collected from all participants, and their bowel functions with SCI were assessed. Microbial diversity and composition were analyzed by sequencing the 16S rRNA gene. The features of gut microbiota correlated with the serum biomarkers and their functions were investigated. The mean NBD score of patients with CTSCI was higher than that of patients with ITSCI. Diversity of the gut microbiota in SCI group was reduced, and with an increase in the degree of damage, alpha diversity had decreased gradually. The composition of gut microbiota in patients with SCI was distinct from that in healthy individuals, and CTSCI group exhibited further deviation than ITSCI group compared to healthy individuals. Four serum biomarkers were found to be correlated with most differential genera. Patients with thoracic SCI present gut dysbiosis, which is more pronounced in patients with CTSCI than in those with ITSCI. Therefore, the gut microbiota profile may serve as the signatures for bowel and motor functions in patients with thoracic SCI., GRAPHICAL ABSTRACT

There is accumulating evidence of a potential beneficial effect of early surgical intervention after acute cervical spinal cord injury (SCI). However, around one third of all SCIs affect the thoracic spine. This cohort has not been extensively investigated, mainly because of less sensitive clinical readout measures. Apart from regaining full sensorimotor function, improvements in bladder and bowel management remain of the highest priority for patients with chronic paraplegia. Therefore, this study investigates the effect of early decompression (here defined as8 hours) versus delayed management on neurologic and functional outcome.We retrospectively analyzed data from the institutional database, in which follow-up data were collected prospectively according to the European Multicenter Study about Spinal Cord Injury standards. Within a 13-year period, we identified 43 patients who met inclusion and exclusion criteria. Of these, 32 (74%) were managed surgically within the first 8 hours. There was a trend toward a higher rate of patients with clinically complete SCI in the early group at baseline.After 1 year, we did not observe a benefit on the neurologic outcome as assessed via the American Spinal Injury Association Impairment Scale grade. Functional outcome was evaluated using the Spinal Cord Independence Measure (SCIM). The early decompressed group demonstrated significantly improved SCIM 6 (i.e., bladder management) (P0.045) and SCIM 9-11 subitems (i.e., mobility, transfer) (P0.019).Early decompression was an independent predictor for improved functional bladder outcome and mobility after 1 year. This effect needs to be studied in future prospective, multicenter studies.

Introduction: Spinal cord injuries (SCI) are major conditions that usually determine severe and permanent dysfunctions, or even important loss of basic functions, generating severe or rather permanent sequels. They can have important chronic consequences such as: tetraplegia or paraplegia.(1). Materials and Methods: This paper presents the case of a young 19-year-old patient who suffered in March 2019, a car accident (passenger) with spinal cord injury (SCI) at cervical and thoracic level in a politraumatic context, hospitalized at the Neurosurgery Clinic (NS) II of TEHBA in a severe condition, for complete AIS/Frankel A tetraplegia, with a C7 fracture, T3, T4, T5 cominutive fractures with fragments in the medullary channel, minor traumatic brain injury, multiple costal fractures, abdominal trauma and respiratory failure. When the patient became hemodynamic and respiratory stable it was decided a neuro-surgical intervention, initially at cervical level through an anterior approach, with mixed osteo-sinthesis and C7 discectomy. Because of the spine instability, thoracic surgical treatment was delayed with 11 days, when he suffers a neurosurgery for medullary decompression, drainage and stabilization of the spine. In our clinical division, the patient was admitted with an incomplete AIS/Frankel B tetraplegia and initially followed a rehabilitation nursing program and subsequently continued with a recovery therapy according to clinical stages. The patient was assessed functionally using the following scales: AIS/Frankel, modified Ashworth, Functional Independence Measure (FIM), Life Quality Assessment (QOL), FAC International Scale, Independence Assessment Scale in Daily Activities (ADL / IADL), Walking Scale for Spinal Cord Injury (WISCI). Results: The patient benefited from a complex neuro-muscular rehabilitation program, having a favorable evolution, with an increase in the evaluated scales scores – passing from AIS/Frankel B classification to a severe AIS/Frankel C stage, and thus, at the moment he is performing walking on short distances, through parallel bars, with long left leg orthosis and support from another person. It was tried a sphincter re-education, but, after urologic examination, because of the important spasticity in the lower limbs and of the urinary catheterization discomfort, it was decided that for a while the patient to remain with fixed urinary catheterization. Conclusions: Even if there is still no cure for SCI sequels, the accurate clinical-functional evaluation, the neurosurgical prompt therapeutic approach, adding complex nursing measures, personalized rehabilitative and kinetotherapy programs, in a young patient with SCI by car accident, determined neuro-locomotor improvements with an increase in patient’s quality of life.(1),(2). Keywords: spinal cord injuries, tetraplegia, traumatism, rehabilitation

Control of voluntary limb movement is predominantly attributed to the contralateral motor cortex. Nevertheless, increasing evidence suggests the involvement of ipsilateral cortical networks in this process. Ipsilateral control particularly emerges in motor tasks requiring bilateral coordination, which is an essential characteristic of locomotion. Here, we combined a unilateral thoracic spinal cord injury (SCI) with a cortical neuroprosthetic intervention that uncovered a functional role of the ipsilateral cortex in rat movement. In all rats, after SCI, ipsilesional cortex excitation promoted a bilateral synergy, whereby the elevation of the contralateral foot was complemented by ipsilateral hindlimb extension. In two animals, we found that stimulation of a medial cortical sub-region modulated ipsilateral hindlimb flexion. Ipsilateral cortical stimulation delivered after SCI alleviated multiple locomotor and postural deficits. These results establish a causal link between cortical activation and a remarkably fine and proportional ipsilateral control of hindlimb movement, a potential target for future neuroprosthetic technology.

Autonomic dysreflexia (AD) is a potentially life-threatening condition that occurs in patients with cervical and high thoracic spinal cord injury (SCI). AD is not completely understood and has a high incidence that increases proportional to the level and severity of the SCI. The signs and symptoms can vary, but severe hypertension is a dominant feature and may be fatal. This condition can be precipitated by a wide range of triggers occurring below the level of the injury, several of which are common to both diagnostic and interventional radiology, such as manipulation or distention of the genitourinary or gastrointestinal tract, patient positioning, or the use of certain anesthetic techniques. There is little guidance in the radiology literature specific to risk stratification or the use of premedication in this population. The incidence and pathophysiology of AD are discussed, along with pragmatic tips to aid the radiologist in selecting patients who may require a higher level of care or anesthesiologist involvement, with instructions for the conservative and medical management of acute episodes of AD.Awareness of AD is essential for all health care practitioners involved in the care of patients with SCI. A variety of procedures in the radiology department, both diagnostic and interventional, may precipitate AD. Planning, monitoring procedures, knowledge of the relevant pathophysiology and pharmacology, and communication with clinical colleagues are essential to ensure safe practice. Clinicians ordering procedures and radiologists selecting protocols for those procedures should identify at-risk patients before booking a procedure to ensure appropriate supervision and anesthesiology support. Education of radiologists, interventional nursing staff, and technical staff can assist in prevention, early recognition, and successful management of AD.

Available online 25 October 2016

Objective The objective was to track and compare the progression of neuroplastic changes in a large animal model and humans with spinal cord injury. Methods A total of 37 individuals with acute traumatic spinal cord injury were followed over time (1, 3, 6, and 12 months post‐injury) with repeated neurophysiological assessments. Somatosensory and motor evoked potentials were recorded in the upper extremities above the level of injury. In a reverse‐translational approach, similar neurophysiological techniques were examined in a porcine model of thoracic spinal cord injury. Twelve Yucatan mini‐pigs underwent a contusive spinal cord injury at T10 and tracked with somatosensory and motor evoked potentials assessments in the fore‐ and hind limbs pre‐ (baseline, post‐laminectomy) and post‐injury (10 min, 3 h, 12 weeks). Results In both humans and pigs, the sensory responses in the cranial coordinates of upper extremities/forelimbs progressively increased from immediately post‐injury to later time points. Motor responses in the forelimbs increased immediately after experimental injury in pigs, remaining elevated at 12 weeks. In humans, motor evoked potentials were significantly higher at 1‐month (and remained so at 1 year) compared to normative values. Conclusions Despite notable differences between experimental models and the human condition, the brain's response to spinal cord injury is remarkably similar between humans and pigs. Our findings further underscore the utility of this large animal model in translational spinal cord injury research.

After acute traumatic spinal cord injury (SCI), the spinal cord can swell to fill the subarachnoid space and become compressed by the surrounding dura. In a porcine model of SCI, we performed a duraplasty to expand the subarachnoid space around the injured spinal cord and evaluated how this influenced acute intraparenchymal hemodynamic and metabolic responses, in addition to histological and behavioral recovery. Female Yucatan pigs underwent a T10 SCI, with or without duraplasty. Using microsensors implanted into the spinal cord parenchyma, changes in blood flow (ΔSCBF), oxygenation (ΔPO

Reproducció del document publicat a: https://doi.org/10.1088/1741-2552/ac19d3, Objective. Impaired trunk stability is frequent in spinal cord injury (SCI), but there is a lack of quantitative measures for assessing trunk function. Our objectives were to: (a) evaluate trunk muscle activity and movement patterns during a reaching task in SCI patients, (b) compare the impact of cervical (cSCI) and thoracic (tSCI) injuries in trunk function, and (c) investigate the effects of a startling acoustic stimulus (SAS) in these patients. Approach. Electromyographic (EMG) and smartphone accelerometer data were recorded from 15 cSCI patients, nine tSCI patients, and 24 healthy controls, during a reaching task requiring trunk tilting. We calculated the response time (RespT) until pressing a target button, EMG onset latencies and amplitudes, and trunk tilt, lateral deviation, and other movement features from accelerometry. Statistical analysis was applied to analyze the effects of group (cSCI, tSCI, control) and condition (SAS, non-SAS) in each outcome measure. Main results. SCI patients, especially those with cSCI, presented significantly longer RespT and EMG onset latencies than controls. Moreover, in SCI patients, forward trunk tilt was accompanied by significant lateral deviation. RespT and EMG latencies were remarkably shortened by the SAS (the so-called StartReact effect) in tSCI patients and controls, but not in cSCI patients, who also showed higher variability. Significance. The combination of EMG and smartphone accelerometer data can provide quantitative measures for the assessment of trunk function in SCI. Our results show deficits in postural control and compensatory strategies employed by SCI patients, including delayed responses and higher lateral deviations, possibly to improve sitting balance. This is the first study investigating the StartReact responses in trunk muscles in SCI patients and shows that the SAS significantly accelerates RespT in tSCI, but not in cSCI, suggesting an increased cortical control exerted by these patients., This work was developed in the framework of the joint project 'Biomedical signal interpretation to study motor impairment, neurological disorders and novel personalised neurorehabilitation therapies', between the Fundación Institut Guttmann and the Institute for Bioengineering of Catalonia. This work was supported in part by a fellowship from 'La Caixa' Foundation (ID 100010434) with fellowship code LCF/BQ/DE18/11670019, in part by the Secretaria d'Universitats i Recerca de la Generalitat de Catalunya under Grant GRC 2017 SGR 01770, in part by the Agencia Estatal de Investigación, the Spanish Ministry of Science, Innovation and Universities, and the European Regional Development Fund under Grant RTI2018 098472-B-I00, in part by the CERCA Program/Generalitat de Catalunya, in part by H2020-ERA-NET Neuron under Grant AC16/00034, in part by La Marató de TV3 2017 under Grant 201713.31, and in part by Premi Beca 'Mike Lane' 2019—Castellers de la Vila de Gràcia. The authors declare no competing interests.

The peak rate of fat oxidation (PFO) achieved during a graded exercise test is an important indicator of metabolic health. In healthy individuals, there is a significant positive association between PFO and total daily fat oxidation (FO). However, conditions resulting in metabolic dysfunction may cause a disconnect between PFO and non-exercise FO. Ten adult men with chronic thoracic spinal cord injury (SCI) completed a graded arm exercise test. On a separate day following an overnight fast (≥ 10 h), they rested for 60 min before ingesting a liquid mixed meal (600 kcal; 35% fat, 50% carbohydrate, 15% protein). Expired gases were collected and indirect calorimetry data used to determine FO at rest, before and after feeding, and during the graded exercise test. Participants had “good” cardiorespiratory fitness (VO2peak: 19.2 ± 5.2 ml/kg/min) based on normative reference values for SCI. There was a strong positive correlation between PFO (0.30 ± 0.08 g/min) and VO2peak (r = 0.86, p = 0.002). Additionally, postabsorptive FO at rest was significantly and positively correlated with postprandial peak FO (r = 0.77, p = 0.01). However, PFO was not significantly associated with postabsorptive FO at rest (0.08 ± 0.02 g/min; p = 0.97), postprandial peak FO (0.10 ± 0.03 g/min; p = 0.43), or incremental area under the curve postprandial FO (p = 0.22). It may be advantageous to assess both postabsorptive FO at rest and PFO in those with SCI to gain a more complete picture of their metabolic flexibility and long-term metabolic health.

There is an increasing need to develop approaches that will not only improve the clinical management of neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI), but also advance therapeutic interventions aimed at recovering bladder function. Although pre-clinical research frequently employs rodent SCI models, large animals such as the pig may play an important translational role in facilitating the development of devices or treatments. Therefore, the objective of this study was to develop a urodynamics protocol to characterize NLUTD in a porcine model of SCI. An iterative process to develop the protocol to perform urodynamics in female Yucatan minipigs began with a group of spinally intact, anesthetized pigs. Subsequently, urodynamic studies were performed in a group of awake, lightly restrained pigs, before and after a contusion-compression SCI at the T2 or T9-T11 spinal cord level. Bladder tissue was obtained for histological analysis at the end of the study. All anesthetized pigs had bladders that were acontractile, which resulted in overflow incontinence once capacity was reached. Uninjured, conscious pigs demonstrated appropriate relaxation and contraction of the external urethral sphincter during the voiding phase. SCI pigs demonstrated neurogenic detrusor overactivity and a significantly elevated post-void residual volume. Relative to the control, SCI bladders were heavier and thicker. The developed urodynamics protocol allows for repetitive evaluation of lower urinary tract function in pigs at different time points post-SCI. This technique manifests the potential for using the pig as an intermediary, large animal model for translational studies in NLUTD.

STUDY DESIGN: Retrospective, case-control study. OBJECTIVES: In a traumatic spinal injury (TSI) cohort from Tanzania, we sought to: (1) describe potential risk factors for pressure ulcer development, (2) present an illustrative case, and (3) propose a low-cost outpatient protocol for prevention and treatment. SETTING: Tertiary referral hospital. METHODS: All patients admitted for TSI over a 33-month period were reviewed. Variables included demographics, time to hospital, injury characteristics, operative management, length of hospitalization, and mortality. Pressure ulcer development was the primary outcome. Regressions were used to report potential predictors, and international guidelines were referenced to construct a low-cost outpatient protocol. RESULTS: Of 267 patients that met the inclusion criteria, 51 developed a pressure ulcer. Length of stay was greater for patients with pressure ulcers compared with those without (45 vs. 30 days, p

Purpose. This study is aimed at investigating brain structural changes and structural network properties in complete spinal cord injury (SCI) patients, as well as their relationship with clinical variables. Materials and Methods. Structural MRI of brain was acquired in 24 complete thoracic SCI patients ( 38.50 ± 11.19 years, 22 males) within the first postinjury year, while 26 age- and gender-matched healthy participants ( 38.38 ± 10.63 years, 24 males) were enrolled as control. The voxel-based morphometry (VBM) approach and graph theoretical network analysis based on cross-subject grey matter volume- (GMV-) based structural covariance networks (SCNs) were conducted to investigate the impact of SCI on brain structure. Partial correlation analysis was performed to explore the relationship between the GMV of structurally changed brain regions and SCI patients’ clinical variables, including injury duration, injury level, Visual Analog Scale (VAS), American Spinal Injury Association Impairment Scale (AIS), International Classification of Functioning, Disability and Health (ICF) scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), after removing the effects of age and gender. Results. Compared with healthy controls, SCI patients showed higher SDS score ( t = 4.392 and p < 0.001 ). In the VBM analysis, significant GMV reduction was found in the left middle frontal cortex, right superior orbital frontal cortex (OFC), and left inferior OFC. No significant difference was found in global network properties between SCI patients and healthy controls. In the regional network properties, significantly higher betweenness centrality (BC) was noted in the right anterior cingulum cortex (ACC) and left inferior OFC and higher nodal degree and efficiency in bilateral middle OFCs, while decreased BC was noted in the right putamen in SCI patients. Only negative correlation was found between GMV of right middle OFC and SDS score in SCI patients ( r = − 0.503 and p = 0.017 ), while no significant correlation between other abnormal brain regions and any of the clinical variables (all p > 0.05 ). Conclusions. SCI patients would experience depressive and/or anxious feelings at the early stage. Their GMV reduction mainly involved psychology-cognition related rather than sensorimotor brain regions. The efficiency of regional information transmission in psychology-cognition regions increased. Greater GMV reduction in psychology region was related with more severe depressive feelings. Therefore, early neuropsychological intervention is suggested to prevent psychological and cognitive dysfunction as well as irreversible brain structure damage.

Individuals living with chronic spinal cord injury (SCI) often exhibit impairments in cognitive function, which impede their rehabilitation and transition into the community. Although a number of clinical studies have demonstrated the impact of impaired cardiovascular control on cognitive impairment, the mechanistic understanding of this deleterious relationship is still lacking. The present study investigates whether chronic disruption of cardiovascular control following experimental SCI results in cerebrovascular decline and vascular cognitive impairment. Fourteen weeks following a high thoracic SCI (at the third thoracic segment), rats were subjected to a battery of in vivo and in vitro physiological assessments, cognitive-behavioral tests, and immunohistochemical approaches to investigate changes in cerebrovascular structure and function in the middle cerebral artery (MCA). We show that in the MCA of rats with SCI, there is a 55% (SCI vs. control: 13.4 ± 1.9% vs. 29.63 ± 2.8%, respectively) reduction in the maximal vasodilator response to carbachol, which is associated with reduced expression of endothelial marker cluster of differentiation 31 (CD31) and transient receptor potential cation channel 4 (TRPV 4) channels. Compared with controls, MCAs in rats with SCI were found to have 50% (SCI vs. control: 1.5 ± 0.2 vs. 1 ± 0.1 a.u., respectively) more collagen 1 in the media of vascular wall and 37% (SCI vs. control: 30.5 ± 2.9% vs. 42.0 ± 4.0%, respectively) less distensibility at physiological intraluminal pressure. Further, the cerebral blood flow (CBF) in the hippocampus was reduced by 32% in the SCI group (SCI vs. control: 44.3 ± 4.5 mL/100 g/min vs. 65.0 ± 7.2 mL/100 g/min, respectively) in association with impairment of short-term memory based on a novel object recognition test. There were no changes in the sympathetic innervation of the vasculature and passive structure in the SCI group. Chronic experimental SCI is associated with structural alterations and endothelial dysfunction in cerebral arteries that likely contribute to significantly reduced CBF and vascular cognitive impairment.

Persons with paraplegia (PA) from thoracic spinal cord injury (T1-T12) are prone to thermal stress during exercise due to impaired thermoregulation. This study evaluates the effectiveness of phase change material (PCM) cooling vests on persons with PA of different levels of injury during exercise in hot exposure. Sixteen participants were recruited and divided to three groups based on injury level; high-thoracic T1-T3, mid-thoracic T4-T8, and low thoracic T9-T12 to perform a 30-min arm-crank exercise at a 30 °C room condition. Two types of PCM vests at melting temperature of 20 °C were tested: i) V1 with PCM covering the trunk of 3.4 kg overall vest mass and ii) V2 with PCM covering chest and upper back of 2.17 kg overall vest mass. High thoracic and low-thoracic groups performed NV and V1 tests; whereas, mid-thoracic group performed NV, V1, and V2 tests. Heart rate, core, and skin temperatures were monitored during 15-min preconditioning, 30-min exercise, and 15-min recovery. In addition, thermal comfort, sensation, skin wettedness, and perceived exertion were recorded during exercise only. The main findings were that the effectiveness of the cooling vest was dependent on injury level and portion of sensate skin of trunk covered by the PCM packets. Rise in core temperature ( Δ T c r ) was reduced significantly for the low-thoracic group during exercise and recovery ( Δ T c r = 0.41 °C , 0.26 °C for NV and V1; respectively, p Δ T c r compared to the NV test at the end of the recovery period ( 0.74 °C , 0.42 °C , 0.56 °C , for NV, V1 and V2; respectively). For the high-thoracic group, V1 was not effective in reducing core temperature (p>0.05). For the mid-thoracic group, V2 at 36% lower mass significantly improved thermal comfort (p = 0.0004) compared to the NV test and was as effective compared to V1 in reducing core temperature.

A mid-thoracic spinal cord injury (SCI) severely impairs activation of the lower limb sensorimotor spinal networks, leading to paralysis. Various neuromodulatory techniques including electrical and pharmacological activation of the spinal networks have been successful in restoring locomotor function after SCI. We hypothesized that the combination of self-training in a natural environment with epidural stimulation (ES), quipazine (Quip), and strychnine (Strych) would result in greater activity in a cage environment after paralysis compared to either intervention alone. To assess this, we developed a method measuring and characterizing the chronic EMG recordings from tibialis anterior (TA) and soleus (Sol) muscles while rats were freely moving in their home cages. We then assessed the relationship between the change in recorded activity over time and motor-evoked potentials (MEPs) in animals receiving treatments. We found that the combination of ES, Quip, and Strych (sqES) generated the greatest level of recovery followed by ES + Quip (qES) while ES + Strych (sES) and ES alone showed least improvement in recorded activity. Further, we observed an exponential relationship between late response (LR) component of the MEPs and spontaneously generated step-like activity. Our data demonstrate the feasibility and potential importance of quantitatively monitoring mechanistic factors linked to activity-dependence in response to combinatorial interventions compared to individual therapies after SCI.

The course, treatment response, and recovery potential after acute traumatic spinal cord injury (SCI) have been shown to differ depending on the neurological level of injury. There are lim...

Spinal cord injury (SCI) leads to the impairment of impulse conduction and subsequently to an abnormality of limbs function. To regain locomotor performance in SCI cases, we establish a robust combinatorial regenerative and rehabilitative approach to enhance axonal regeneration in the Sprague-Dawley rat with complete thoracic SCI. This system consists of a body weight support system, five-bar linkage for driving the rat's ankles, and treadmill for training motor functions. This system is tested in a rat which is totally transected at T9 and T10 of the spinal cord. A nanofiber scaffold is implanted in a gap between T9 and T10 of the spinal cord in a spinalized rat for stimulating axonal regrowth. The position errors are quantified under five static load conditions (no load, 10, 30, 60, and 100 g) and dynamic load condition. Average root mean square (RMS) position errors in x - and y- axes of the manipulator are 2.1% and 5.3%, respectively. According to a preliminary test, this system can provide the constant force to support the body weight and can drive the rat's hindlimbs without inducing anxiety or irritation. From our experiment, average RMS position errors in x - and y- axes of the manipulator are 10% and 11.7%, respectively. The contribution of this research is the developmental rehabilitation robotic system for a rat with complete thoracic SCI in quadruped posture which can provide more natural walking posture. The scope of this letter is a developmental rehabilitation robotic system.

The safety and efficacy of pharmacological and cellular transplantation strategies are currently being evaluated in people with spinal cord injury (SCI). In studies of people with chronic SCIs, it is thought that functional recovery will be best achieved when drug or cell therapies are combined with rehabilitation protocols. However, any functional recovery attributed to the therapy may be confounded by the conditioned state of the body and by training-induced effects on neuroplasticity. For this reason, we sought to investigate the effects of a multi-modal training program on several body systems. The training program included body-weight–supported treadmill training for locomotion, circuit resistance training for upper body conditioning, functional electrical stimulation for activation of sublesional muscles, and wheelchair skills training for overall mobility. Eight participants with chronic, thoracic-level, motor-complete SCI completed the 12-week training program. After 12 weeks, upper extremity muscular strength improved significantly for all participants, and some participants experienced improvements in function, which may be explained by increased strength. Neurological function did not change. Changes in pain and spasticity were highly variable between participants. This is the first demonstration of the effect of this combination of four training modalities. However, balancing participant and study-site burden with capturing meaningful outcome measures is also an important consideration.

Study design Randomized experimental study. Objective Compared to able-bodied people, patients with paraplegia due to thoracic spinal cord injury (SCI) are at an increased risk of heat illnesses during exercise due to impaired thermoregulatory responses. To overcome this limitation, we investigated the performance of three phase change material (PCM) cooling vests of different melting temperatures (Eijsvogels, #49) and coverage area of the trunk. Methods Sixteen participants were divided into three groups according to their injury level. All were tested for V20 full vest (20°C Tm, 75% coverage). Mid-thoracic and high-thoracic groups were tested for V14 vest (14°C Tm, 75% coverage). The mid-thoracic group was tested for V20 half vest (20°C Tm, 50% coverage). The participants performed a 30-min arm-crank exercise followed by a recovery period inside a controlled hot climatic chamber. The heart rate, segmental skin (Tskin), and core temperature (Tcore) values were recorded, and subjective questionnaires were taken. Results Compared to no vest (NV) test, all the vests showed an effective decrease in Tskin values of the trunk. However, the decrease in Tskin was not enough to induce a significant decrease in Tcore in all three groups. Mid-thoracic and low-thoracic groups showed a reduction in the increasing Tcore by the end of the exercise and recovery period. Finally, the level of thermal comfort was enhanced for the three groups. Conclusion The effectiveness of cooling vests for persons with paraplegia is dependent on injury level and thus the ratio of sensate to insensate skin. Future studies necessitate the investigation of the cooling effects of PCM vests at a lower Tm with a larger sample size.

Thoracic spinal cord injury (SCI) can have significant negative consequences, which can affect the ability to maintain unsupported sitting. The objectives of this study were to compare postural control of individuals with high- and low-thoracic SCI to able-bodied people and evaluate the effects of upper-limb support on postural control during quiet sitting. Twenty-five individuals were recruited into: (a) high-thoracic SCI; (b) low-thoracic SCI; and (c) able-body subgroups. Participants were seated and asked to maintain a steady balance in the following postures: (1) both hands resting on thighs; (2) both arms crossed over the chest; and (3) both arms extended. Center of pressure (COP) fluctuations were evaluated to compare postural performance between groups and different postures. Results showed that individuals with high- and low-thoracic SCI swayed more compared to the able-bodied group regardless of upper-limb support. No differences between the two SCI groups were observed, but the neurological level of injury was correlated to postural performance implying that those with higher injuries swayed more and faster. Unsupported sitting was more unstable in comparison to supported sitting posture, especially in the anterior-posterior direction. The velocity of postural sway was not different between groups, but the results suggest that postural regulation had unique effect during different postures in different groups. These results imply reduced postural stability after thoracic SCI. Overall, the way individuals with high-thoracic SCI achieved stability was different from that of individuals with low-thoracic SCI, suggesting different postural regulation strategies.

BACKGROUND The lifetime economic burden of thoracic spinal cord injury (SCI) is known to be high, but evidence of variability of costs in relation to the American Spinal Injury Association Impairment Scale (AIS) grade is limited. OBJECTIVE To estimate lifetime economic costs of hospitalization by AIS grade in thoracic SCI. METHODS Using SCI Model Systems data from January 2000 to March 2016 from the National Spinal Cord Injury Statistical Center, we estimated mean total annual days of all-cause hospitalization by AIS grade among persons with thoracic SCI, based on assessments 1, 5, and 10 yr post-injury. We combined this information with secondary cost data and projections of life expectancy to estimate lifetime economic costs of hospitalization by AIS grade in persons aged 35 yr at time of thoracic SCI. Future costs were discounted to present value at 3% annually. RESULTS One year post-injury, mean total annual days of hospitalization ranged from 2.1 for persons with AIS-D injuries to 5.9 for those who were AIS-A. Similar differences were noted 5 and 10 yr post-SCI. The estimated net present value of expected lifetime costs of hospitalization following thoracic SCI at age 35 yr was $321 534, $249 514, $188 989, and $68 120 (2015 US$) for AIS-A, AIS-B, AIS-C, and AIS-D injuries, respectively. CONCLUSION Persons with less severe thoracic SCI, as reflected in AIS grade, spend fewer days in hospital over their lifetimes, leading to lower costs of inpatient care. Therapies improving AIS grade following thoracic SCI may provide cost savings in addition to addressing substantial unmet need.

Summary We previously showed the efficacy of multiple research cell lines (RCLs) of human CNS neural stem cells (HuCNS-SCs) in mouse and rat models of thoracic spinal cord injury (SCI), supporting a thoracic SCI clinical trial. Experts recommend in vivo preclinical testing of the intended clinical cell lot/line (CCL) in models with validity for the planned clinical target. We therefore tested the efficacy of two HuCNS-SC lines in cervical SCI: one RCL, and one CCL intended for use in the Pathway Study of cervical SCI in man. We assessed locomotor recovery and sensory function, as well as engraftment, migration, and fate. No evidence of efficacy of the CCL was observed; some data suggested a negative impact of the CCL on outcomes. These data raise questions about the development and validation of potency/comparability assays for clinical testing of cell products, and lack of US Food and Drug Administration requirements for in vivo testing of intended clinical cell lines., Graphical Abstract, Highlights • Human CNS stem cells (HuCNS-SCs) have been used in multiple clinical trials • Research cell lines of HuCNS-SCs are efficacious in spinal cord injury (SCI) models • The clinical cell line (CCL) of HuCNS-SC was not efficacious in a cervical SCI model • Despite lack of in vivo efficacy, the CCL was used in the Pathways clinical study, Anderson and colleagues report that preclinical testing of a human neural stem cell line intended for use in a human clinical trial of cervical spinal cord injury (SCI) failed to show efficacy in an animal model of SCI, whereas a research-grade cell line did show efficacy. The human trial proceeded despite the negative data.

Cervical and high thoracic spinal cord injury (SCI) drastically impairs autonomic nervous system function. Individuals with SCI at thoracic spinal level 5 (T5) or higher often present cardiovascular disorders that include resting systemic arterial hypotension. Gastrointestinal (GI) tissues are critically dependent upon adequate blood flow and even brief periods of visceral hypoxia triggers GI dysmotility. The aim of this study was to test the hypothesis that T3-SCI induces visceral hypoperfusion, diminished postprandial vascular reflexes, and concomitant visceral inflammation. We measured in vivo systemic arterial blood pressure and superior mesenteric artery (SMA) and duodenal blood flow in anesthetized T3-SCI rats at 3 days and 3 wk postinjury either fasted or following enteral feeding of a liquid mixed-nutrient meal (Ensure). In separate cohorts of fasted T3-SCI rats, markers of intestinal inflammation were assayed by qRT-PCR. Our results show that T3-SCI rats displayed significantly reduced SMA blood flow under all experimental conditions ( P < 0.05). Specifically, the anticipated elevation of SMA blood flow in response to duodenal nutrient infusion (postprandial hyperemia) was either delayed or absent after T3-SCI. The dysregulated SMA blood flow in acutely injured T3-SCI rats coincides with abnormal intestinal morphology and elevation of inflammatory markers, all of which resolve after 3 wk. Specifically, Icam1, Ccl2 (MCP-1), and Ccl3 (MIP-1α) were acutely elevated following T3-SCI. Our data suggest that arterial hypotension diminishes mesenteric blood flow necessary to meet mucosal demands at rest and during digestion. The resulting GI ischemia and low-grade inflammation may be an underlying pathology leading to GI dysfunction seen following acute T3-SCI.

Studies using rodent models of neuropathic pain use sham surgery control procedures that cause deep tissue damage. Sham surgeries would thus be expected to induce potentially long-lasting postsurgical pain, but little evidence for such pain has been reported. Operant tests of voluntary behavior can reveal negative motivational and cognitive aspects of pain that may provide sensitive tools for detecting pain-related alterations. In a previously described operant mechanical conflict test involving lengthy familiarization and training, rodents freely choose to either escape from a brightly lit chamber by crossing sharp probes or refuse to cross. Here, we describe a brief (2-day) mechanical conflict protocol that exploits rats' innate exploratory response to a novel environment to detect persistently enhanced pain-avoidance behavior after sham surgeries for 2 neural injury models: thoracic spinal cord injury and chronic constriction injury of the sciatic nerve. Pitting the combined motivations to avoid the bright light and to explore the novel device against pain from crossing noxious probes disclosed a conflicting, hyperalgesia-related reluctance to repeatedly cross the probes after injury. Rats receiving standard sham surgeries demonstrated enhanced pain-like avoidance behavior compared with naive controls, and this behavior was similar to that of corresponding chronic constriction injury or spinal cord injury rats weeks or months after injury. In the case of sham surgery for spinal cord injury, video analysis of voluntary exploratory behavior directed at the probes revealed enhanced forepaw withdrawal responses. These findings have important implications for preclinical investigations into behavioral alterations and physiological mechanisms associated with postsurgical and neuropathic pain.

The impact of surgical timing in neurological recovery in thoracic and thoracolumbar traumatic spinal cord injury (tSCI) is still a subject of discussion. While in cervical tSCI one may expect a beneficial effect of early intervention within 24 h, especially in complete cases, this has not yet been demonstrated clearly for thoracic tSCI. This study addresses neurological improvement after early and late surgery for thoracic and thoracolumbar tSCI. A systematic search retrieved 14 publications of observational studies reporting outcome measurements after surgery in 1075 patients with thoracic and thoracolumbar tSCI from PubMed and Embase databases. Surgery was considered early within 24 h and late thereafter. An improvement of at least one and two grades on the American Spinal Injury Association Impairment Scale (ASIA) was evaluated. The Meta-Analyses and Systematic Reviews of Observational Studies guidelines were followed. Improvement rates were summarized using individual patient data in a Bayesian random effects model and compared for those with early and late surgery. In the qualitative analysis, six of seven studies, which investigated the effect of surgical timing, observed a significant effect of early surgery on at least one ASIA grade improvement. Quantitative analysis in 948 patients with thoracic and thoracolumbar tSCI data, however, did not reveal a significant increase in odds of ≥1 ASIA grade recovery in early surgery (66.8% [95% confidence interval (CI): 45.0-87.8%] compared with late surgery (48.9% [95% CI: 25.1-70.7%; odds ratio (OR) 2.2 (95% CI: 0.6-14.0]). This study did not observe a significant beneficial effect of surgical decompression within 24 h in patients with thoracic and thoracolumbar tSCI.

Introduction Cognitive impairment is present in 64% individuals with spinal cord injury (SCI), affecting their attention, memory, learning and studying abilities, which are essential for post-injur...

[Purpose] To investigate the influence of the level of spinal cord injury on the thermic effect of food intake (TEF) in persons with thoracic spinal cord injury. [Subjects and Methods] Seven male subjects with spinal cord injury (SCI; age, 40 ± 6 years) and six able-bodied subjects (AB; age, 37 ± 8 years) volunteered to participate in the present study. The subjects consumed an identical test meal consisting of 7.9 kcal/kg of body weight. Energy expenditure and plasma norepinephrine concentrations were measured over a 3-hour period. [Results] The adjusted TEF at 60 min was almost the same among the three groups [AB, SCI with high thoracic cord (T5–6) injury (HSCI), and SCI with low thoracic cord (T9–12) injury (LSCI)]. Although the LSCI group had almost the same adjusted TEF at 120 min as the AB group, the adjusted TEF at 120 min of the HSCI group was significantly lower than that of the AB group. The changes in plasma norepinephrine concentration and heart rate in response to food intake were similar among the three groups. [Conclusion] SCI at the T5–6 level results in a lower TEF due to sympathetic decentralization.