Locomotor Outcome Research Articles

The Locomotor Movement Abilities of Children Aged 5-6 Years in Terms of Geographical Aspects (Coastal and Mountain Areas)

This study examines the differences in locomotor abilities of children aged 5-6 years in two locations, namely coastal and mountainous areas in Kebumen City, Indonesia. This is important because children's locomotor outcomes are still poor and there has been no identification of locomotor abilities judging from previous studies that only examined manipulative movement abilities. Overall, this study contributes greatly to future research by providing important insights into how environmental and geographical factors interact with children's physical development, which in turn can aid in the creation of more effective policies and interventions to support holistic child development. Using descriptive research methods, the population was 40 schools specifically for coastal and mountainous areas, then sampling was carried out in 2 stages, namely using cluster random sampling techniques and then purposive sampling. The sample size was 130 with details of 65 children in coastal areas and 65 in mountainous regions. This instrument has been validated and reliable on 135 children in Indonesia with a validity result of 2.27 > t table 1.65 and reliability of 0.765. The statistical test results showed a p value = 0.013 which means that there is a relationship between children's locomotor abilities with geography in the two different locations, namely mountains and coasts. The average child's locomotor ability in coastal areas was found to be superior compared to mountainous areas.

Looking back over the shoulder: New insights on the unique scapular anatomy of the tapir (Perissodactyla: Tapiridae).

The musculoskeletal anatomy of the shoulder of many ungulates has been inferred from veterinary model taxa, with uniformity in muscle arrangements and attachment sites often assumed. In this study, I investigated the muscular and osteological anatomy of tapirs and their relatives (Perissodactyla: Tapiroidea), using a combination of gross dissection and digital imaging (photography and laser surface scanning). Dissections of three modern tapir species revealed that the m. infraspinatus originates from both supraspinous and infraspinous fossae for all species, lying on both sides of the distal scapular spine. The epimysial border between the m. supraspinatus and m. infraspinatus origin sites are marked in all species by an ossified ridge, sometimes extending the length of the scapular spine. This "supraspinous ridge" is clearly visible on the scapular surface of both modern and extinct Tapirus scapulae; however, the ridge does not appear present in any non-Tapirus tapiroids examined (e.g., Helaletes, Nexuotapirus), nor in other perissodactyls or artiodactyls. Moreover, the ridge exhibits a clearly distinct morphology in Tapirus indicus compared to all other Tapirus species examined. Combined, these findings indicate that the presence and position of the "supraspinous ridge" may represent a robust phylogenetic character for reconstructing relationships within tapiroids. Unfortunately, any functional locomotor outcomes or benefits of the m. infraspinatus straddling the scapular spine remains elusive. This study represents a firm reminder for anatomists, veterinarians, and paleontologists to (where possible) look beyond veterinary model systems when inferring musculoskeletal form or function in non-model organisms.

Influence of surgical masks on the avoidance of virtual pedestrians

To combat the COVID-19 pandemic, governments around the world have proposed a series of mitigation strategies. While responses varied across different governing bodies, recommendations such as social distancing and the use of surgical masks were nearly universal. These recommendations, as well as the social anxiety that emerged during the pandemic, are likely to have influenced pedestrian interactions. In this study, we have examined the effect of surgical masks on locomotor circumvention strategies in response to virtual pedestrians. We further explored the relationship between measures of obstacle clearance and feelings of anxiety related to community ambulation in the context of the pandemic. Using virtual reality, locomotor circumvention strategies in response to approaching pedestrians with and without surgical masks were measured in a sample of 11 healthy young individuals. Additionally, a questionnaire was developed and used to gain insights into participants’ behaviours during and after a strict period of restrictions that were in effect before the summer of 2020. Results showed that participants maintained a larger clearance when virtual pedestrians wore a surgical mask. Furthermore, clearance was positively associated with anxiety toward community ambulation in the context of the pandemic. Our findings provide evidence that mask-wearing elicits an increase in physical distancing during pedestrian interactions. Furthermore, results indicate that social context and mental health status influence locomotor outcomes measured in the context of a pedestrian interaction task and highlight the potential of virtual reality simulations to study locomotion in the community setting.

Unintentional Effects from Housing Enhancement Resulting in Functional Improvement in Spinal Cord-Injured Mice.

It is well established that both positive and negative housing conditions of laboratory animals can affect behavioral, biochemical, and physiological responses. Housing enhancements have been shown to have beneficial effects on locomotor outcomes in rodents with spinal cord injury (SCI). Subsequent to an unplanned housing enhancement of the addition of a balcony to home cages by animal care personnel at a research facility, a retrospective analysis of multiple SCI studies was performed to determine whether outcomes differed before (four studies, N = 28) and after (four studies, N = 23) the addition of the balcony. Locomotor and morphological differences were compared after a mild-moderate T9 spinal cord contusion injury in wild-type mice. Post-injury assessments of locomotor function for 6 weeks included Basso Mouse Scale (BMS) and treadmill kinematic assessments (week 6). Balcony-housed mice showed greater improvements not only in basic locomotor functions (weight-supported stepping, balance) compared to those in standard housing, but also surpassed mice in standard housing without the balcony in higher-order locomotor recovery outcomes, including BMS late-stage recovery measures (paw, tail, and trunk indices). Additionally, balcony-housed mice had overall higher BMS scores, consistently attained more BMS subscores, and had better treadmill track width and stride length compared to those with no balcony. The housing enhancement of a balcony led to unforeseen consequences and unexpected higher recovery outcomes compared to mice in standard housing. This retrospective study highlights the importance of housing conditions in the key outcomes of locomotor recovery after incomplete contusive SCIs in mice.

Differential Trajectory of Diffusion and Perfusion Magnetic Resonance Imaging of Rat Spinal Cord Injury.

Traumatic spinal cord injury causes rapid neuronal and vascular injury, and predictive biomarkers are needed to facilitate acute patient management. This study examined the progression of magnetic resonance imaging (MRI) biomarkers after spinal cord injury and their ability to predict long-term neurological outcomes in a rodent model, with an emphasis on diffusion-weighted imaging (DWI) markers of axonal injury and perfusion-weighted imaging of spinal cord blood flow (SCBF). Adult Sprague-Dawley rats received a cervical contusion injury of varying severity (injured = 30, sham = 9). MRI at 4 h, 48-h, and 12-weeks post-injury included T1, T2, perfusion, and DWI. Locomotor outcome was assessed up to 12 weeks post-injury. At 4 h, the deficit in SCBF was larger than the DWI lesion, and although SCBF partially recovered by 48 h, the DWI lesion expanded. At 4 h, the volume of the SCBF deficit (R2 = 0.56, padj < 0.01) was significantly correlated with 12-week locomotor outcome, whereas DWI (R2 = 0.30, padj < 0.01) was less predictive of outcome. At 48 h, SCBF (R2 = 0.41, padj < 0.01) became less associated with outcome, and DWI (R2 = 0.38, padj < 0.01) lesion volume became more closely related to outcome. Spinal cord perfusion has unique spatiotemporal dynamics compared with diffusion measures of axonal damage and highlights the importance of acute perfusion abnormalities. Perfusion and diffusion offer complementary and clinically relevant insight into physiological and structural abnormalities following spinal cord injury beyond those afforded by T1 or T2 contrasts.

Effect of Acute Physical Interventions on Pathophysiology and Recovery After Spinal Cord Injury: A Comprehensive Review of the Literature.

Physical rehabilitation is essential for enhancing recovery in individuals with spinal cord injury (SCI); however, aside from early surgical intervention and hemodynamic management, there are no proven interventions for promoting recovery in the acute phase. In general, early rehabilitation is considered beneficial, but optimal parameters and potential contraindications for implementing rehabilitation at very early time points are unclear. Moreover, clinical trials to date are limited to studies initiating rehabilitation 2 weeks after injury and later. To address these gaps, this article reviews the preclinical literature on physical interventions initiated within the first 8 days postinjury. Effects of early rehabilitation on molecular and structural nervous system changes, behavioral function, and body systems are considered. Most studies utilized treadmill or cycle training as the primary intervention. Treadmill training initiated within the first 3 days and terminated by 1 week after injury worsened autonomic function, inflammation, and locomotor outcomes, while swim training during this period increased microvascular dysfunction. In contrast, lower-intensity rehabilitation such as reach training, ladder training, or voluntary wheel or ball training showed benefits when implemented during the first 3 days. Rehabilitation initiated at 4 days postinjury was also associated with enhanced motor recovery. Cycling appears to have the greatest risk-benefit ratio; however, the effects of cycle training in the first 3 days were not investigated. Overall, research suggests that lower intensity or voluntary rehabilitation during the hyperacute phase is more appropriate until at least 4 days postinjury, at which point higher-intensity activity becomes safer and more beneficial for recovery.

Increasing the Amount and Intensity of Stepping Training During Inpatient Stroke Rehabilitation Improves Locomotor and Non-Locomotor Outcomes

Background The efficacy of traditional rehabilitation interventions to improve locomotion post-stroke, including providing multiple exercises targeting impairments and activity limitations, is uncertain. Emerging evidence rather suggests attempts to prioritize stepping practice at higher cardiovascular intensities may facilitate greater locomotor outcomes. Objective The present study was designed to evaluate the comparative effectiveness of high-intensity training (HIT) to usual care during inpatient rehabilitation post-stroke. Methods Changes in stepping activity and functional outcomes were compared over 9 months during usual-care (n = 131 patients < 2 months post-stroke), during an 18-month transition phase with attempts to implement HIT (n = 317), and over 12 months following HIT implementation (n = 208). The transition phase began with didactic and hands-on education, and continued with meetings, mentoring, and audit and feedback. Fidelity metrics included percentage of sessions prioritizing gait interventions and documenting intensity. Demographics, training measures, and outcomes were compared across phases using linear or logistic regression analysis, Kruskal-Wallis tests, or χ2 analysis. Results Across all phases, admission scores were similar except for balance (usual-care>HIT; P < .02). Efforts to prioritize stepping and achieve targeted intensities during HIT vs transition or usual-care phases led to increased steps/day (P < .01). During HIT, gains in 10-m walk [HIT median = 0.13 m/s (interquartile range: 0-0.35) vs usual-care = 0.07 m/s (0-0.24), P = .01] and 6-min walk [50 (9.3-116) vs 2.1 (0-56) m, P < .01] were observed, with additional improvements in transfers and stair-climbing. Conclusions Greater efforts to prioritize walking and reach higher intensities during HIT led to increased steps/day, resulting in greater gains in locomotor and non-locomotor outcomes.

Ultrasound Measurements of Rectus Femoris and Locomotor Outcomes in Patients with Spinal Cord Injury.

Patients with incomplete spinal cord injury have decreased mobility, and many do not recover walking ability. The purpose of this study was to investigate rectus femoris muscle thickness and echo intensity on ultrasound and functional outcomes in these patients. This was a prospective cohort study in an inpatient rehabilitation center, which recruited 40 consecutive patients with incomplete spinal cord injury. The patients underwent an ultrasound assessment at 6 weeks post-injury. Ultrasound measurements were performed using B-mode ultrasound scanning and standardized protocols. Functional outcomes on discharge, including Lower Extremity Muscle Score (LEMS), Functional Independence Measure (FIM), and Walking Index for Spinal Cord Injury II (WISCI II), were measured. Rectus femoris muscle thickness was significantly correlated with discharge LEMS (Spearman’s rho = 0.448; p = 0.004), FIM motor subscale (Spearman’s rho = 0.595; p < 0.001), FIM walk subscale (Spearman’s rho = 0.621; p < 0.001) and WISCI II (Spearman’s rho = 0.531; p < 0.001). The rectus femoris echo intensity was also significantly correlated with discharge LEMS (Spearman’s rho = −0.345; p = 0.029), FIM motor subscale (Spearman’s rho = −0.413; p = 0.008), FIM walk subscale (Spearman’s rho = −0.352; p = 0.026), and WISCI II (Spearman’s rho = −0.355; p = 0.025). We report that a relationship exists between rectus femoris muscle ultrasonographic characteristics and muscle function and ambulatory outcomes after inpatient rehabilitation. Ultrasound muscle measurements are potentially useful in assessing muscle wasting and function in patients with spinal cord injury.

Early Care and Education Center Environmental Factors Associated with Product- and Process-Based Locomotor Outcomes in Preschool-Age Children.

Environmental characteristics of early care and education centers (ECECs) are an important context for preschool-aged children’s development, but few studies have examined their relationship with children’s locomotor skills. We examined the association between characteristics of the ECEC environment with quantitatively (i.e., product-based) and qualitatively (i.e., process-based) measured locomotor skills, using the Progressive Aerobic Cardiovascular Endurance Run (PACER) and the locomotor portion of the Children’s Activity and Movement in Preschool Study (CHAMPS) motor skills protocol (CMSP), respectively. ECEC characteristics included outdoor and indoor play environment quality, outdoor and indoor play equipment, screen-time environment quality, and policy environment quality. Mean (SD) scores for the PACER (n = 142) and CSMP (n = 91) were 3.7 ± 2.3 laps and 19.0 ± 5.5 criteria, respectively, which were moderately correlated with each other (Pearson r = 0.5; p < 0.001). Linear regression models revelated that a better policy environment score was associated with fewer PACER laps. Better outdoor play and screen-time environment quality scores and more outdoor play equipment were positively associated with higher CMSP scores. ECEC environments that reflect best practice guidelines may be opportunities for locomotor skills development in preschool-aged children. ClinicalTrials.gov Identifier: NCT03261492 (8/25/17).

Step Monitor Accuracy During PostStroke Physical Therapy and Simulated Activities.

The amount of stepping activity during rehabilitation post-stroke can predict walking outcomes, although the most accurate methods to evaluate stepping activity are uncertain with conflicting findings on available stepping monitors during walking assessments. Rehabilitation sessions also include non-stepping activities and the ability of activity monitors to differentiate these activities from stepping is unclear. The objective of this study was to examine the accuracy of different activity monitors worn by individuals post-stroke with variable walking speeds during clinical physical therapy (PT) and research interventions focused on walking. In Part I, 28 participants post-stroke wore a StepWatch, ActiGraph with and without a Low Frequency Extension (LFE) filter, and Fitbit on paretic and non-paretic distal shanks at or above the ankle during clinical PT or research interventions with steps simultaneously hand counted. Mean absolute percent errors were compared between limbs and tasks performed. In Part II, 12 healthy adults completed 8 walking and 9 non-walking tasks observed during clinical PT or research. Data were descriptively analyzed and used to assist interpretation of Part I results. Part I results indicate most devices did not demonstrate an optimal limb configuration during research sessions focused on walking, with larger errors during clinical PT on the non-paretic limb. Using the limb that minimized errors for each device, the StepWatch had smaller errors than the ActiGraph and Fitbit (p<0.01), particularly in those who walked < 0.8 m/s. Conversely, errors from the ActiGraph-LFE demonstrated inconsistent differences in step counts between Fitbit and ActiGraph. Part II results indicate that errors observed during different stepping and non-stepping activities were often device-specific, with non-stepping tasks frequently detected as stepping. The StepWatch and ActiGraph-LFE had smaller errors than the Fitbit or ActiGraph, with greater errors in those walking at slower speeds. Inclusion of non-stepping activities affected step counts and should be considered when measuring stepping activity in individuals post-stroke to predict locomotor outcomes following rehabilitation.

Split-Belt Training but Not Cerebellar Anodal tDCS Improves Stability Control and Reduces Risk of Fall in Patients with Multiple Sclerosis.

The objective of this study was to examine the therapeutic potential of multiple sessions of training on a split-belt treadmill (SBT) combined with cerebellar anodal transcranial direct current stimulation (tDCS) on gait and balance in People with Multiple Sclerosis (PwMS). Twenty-two PwMS received six sessions of anodal (PwMSreal, n = 12) or sham (PwMSsham, n = 10) tDCS to the cerebellum prior to performing the locomotor adaptation task on the SBT. To evaluate the effect of the intervention, functional gait assessment (FGA) scores and distance walked in 2 min (2MWT) were measured at the baseline (T0), day 6 (T5), and at the 4-week follow up (T6). Locomotor performance and changes of motor outcomes were similar in PwMSreal and PwMSsham independently from tDCS mode applied to the cerebellum (anodal vs. sham, on FGA, p = 0.23; and 2MWT, p = 0.49). When the data were pooled across the groups to investigate the effects of multiple sessions of SBT training alone, significant improvement of gait and balance was found on T5 and T6, respectively, relative to baseline (FGA, p < 0.001 for both time points). The FGA change at T6 was significantly higher than at T5 (p = 0.01) underlining a long-lasting improvement. An improvement of the distance walked during the 2MWT was also observed on T5 and T6 relative to T0 (p = 0.002). Multiple sessions of SBT training resulted in a lasting improvement of gait stability and endurance, thus potentially reducing the risk of fall as measured by FGA and 2MWT. Application of cerebellar tDCS during SBT walking had no additional effect on locomotor outcomes.

Corticospinal Motor Circuit Plasticity After Spinal Cord Injury: Harnessing Neuroplasticity to Improve Functional Outcomes.

Spinal cord injury (SCI) is a devastating condition that affects approximately 294,000 people in the USA and several millions worldwide. The corticospinal motor circuitry plays a major role in controlling skilled movements and in planning and coordinating movements in mammals and can be damaged by SCI. While axonal regeneration of injured fibers over long distances is scarce in the adult CNS, substantial spontaneous neural reorganization and plasticity in the spared corticospinal motor circuitry has been shown in experimental SCI models, associated with functional recovery. Beneficially harnessing this neuroplasticity of the corticospinal motor circuitry represents a highly promising therapeutic approach for improving locomotor outcomes after SCI. Several different strategies have been used to date for this purpose including neuromodulation (spinal cord/brain stimulation strategies and brain-machine interfaces), rehabilitative training (targeting activity-dependent plasticity), stem cells and biological scaffolds, neuroregenerative/neuroprotective pharmacotherapies, and light-based therapies like photodynamic therapy (PDT) and photobiomodulation (PMBT). This review provides an overview of the spontaneous reorganization and neuroplasticity in the corticospinal motor circuitry after SCI and summarizes the various therapeutic approaches used to beneficially harness this neuroplasticity for functional recovery after SCI in preclinical animal model and clinical human patients' studies.

Addition of angled rungs to the horizontal ladder walking task for more sensitive probing of sensorimotor changes.

One method for the evaluation of sensorimotor therapeutic interventions, the horizontal ladder walking task, analyzes locomotor changes that may occur after disease, injury, or by external manipulation. Although this task is well suited for detection of large effects, it may overlook smaller changes. The inability to detect small effect sizes may be due to a neural compensatory mechanism known as “cross limb transfer”, or the contribution of the contralateral limb to estimate an injured or perturbed limb’s position. The robust transfer of compensation from the contralateral limb may obscure subtle locomotor outcomes that are evoked by clinically relevant therapies, in the early onset of disease, or between higher levels of recovery. Here, we propose angled rungs as a novel modification to the horizontal ladder walking task. Easily-adjustable angled rungs force rats to locomote across a different locomotion path for each hindlimb and may therefore make information from the contralateral limb less useful. Using hM3Dq (excitatory) Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) expressed in large diameter peripheral afferents of the hindlimb in the intact animal, we characterized the sensitivity of our design to detect stepping differences by comparing locomotor changes observed on angled rungs to those observed on a standard horizontal ladder. On our novel asymmetrical ladder, activation of DREADDs resulted in significant differences in rung misses (p = 0.000011) and weight-supporting events (p = 0.049). By comparison, on a standard ladder, we did not observe differences in these parameters (p = 0.86 and p = 0.98, respectively). Additionally, no locomotor differences were detected in baseline and inactivated DREADDs trials when we compared ladder types, suggesting that the angled rungs do not change animal gait behavior unless intervention or injury is introduced. Significant changes observed with angled rungs may demonstrate more sensitive probing of locomotor changes due to the decoupling of cross limb transfer.

Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study

BackgroundTraumatic brain injury (TBI) is a major cause of morbidity and mortality, but there are no clinically proven treatments that specifically target neuronal loss and secondary injury development following TBI. In this study, we evaluate the effect of xenon treatment on functional outcome, lesion volume, neuronal loss and neuroinflammation after severe TBI in rats.MethodsYoung adult male Sprague Dawley rats were subjected to controlled cortical impact (CCI) brain trauma or sham surgery followed by treatment with either 50% xenon:25% oxygen balance nitrogen, or control gas 75% nitrogen:25% oxygen. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24 h after injury. Histological outcomes were assessed following perfusion fixation at 15 min or 24 h after injury or sham procedure.ResultsXenon treatment reduced lesion volume, reduced early locomotor deficits, and attenuated neuronal loss in clinically relevant cortical and subcortical areas. Xenon treatment resulted in significant increases in Iba1-positive microglia and GFAP-positive reactive astrocytes that was associated with neuronal preservation.ConclusionsOur findings demonstrate that xenon improves functional outcome and reduces neuronal loss after brain trauma in rats. Neuronal preservation was associated with a xenon-induced enhancement of microglial cell numbers and astrocyte activation, consistent with a role for early beneficial neuroinflammation in xenon’s neuroprotective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma.

Intensive Locomotor Training Provides Sustained Alleviation of Chronic Spinal Cord Injury-Associated Neuropathic Pain: A Two-Year Pre-Clinical Study.

Neuropathic pain often accompanies the functional deficits associated with spinal cord injury (SCI) and further reduces a patient's quality of life. Clinical and pre-clinical research is beginning to highlight the beneficial role that rehabilitative therapies such as locomotor training can have not only on functional recovery but also on chronic pain management. Our group has previously developed an intensive locomotor training (ILT) treadmill protocol on rats that reduced SCI neuropathic pain symptoms for at least 3 months. We have extended these findings in the current study to evaluate the ability of regular ILT regimen over a 2 year period post-SCI to maintain neuropathic pain reduction. To assess this, the rat clip compression SCI model (T7/8) was used and treadmill training was initiated starting 4 weeks after SCI and continuing through the duration of the study. Results showed continued suppression of SCI neuropathic pain responses (reduced mechanical, heat, and cold hypersensitivity throughout the entire time course of the study). In contrast, non-exercised rats showed consistent and sustained neuropathic pain responses during this period. In addition, prolonged survival and improved locomotor outcomes were observed in rats undergoing ILT as the study longevity progressed. Potential contributory mechanisms underlying beneficial effects of ILT include reduced inflammation and restoration of anti-nociceptive inhibitory processes as indicated by neurochemical assays in spinal tissue of remaining rats at 2 years post-SCI. The benefits of chronic ILT suggest that long-term physical exercise therapy can produce powerful and prolonged management of neuropathic pain, partly through sustained reduction of spinal pathological processes.

Stepwise Regression and Latent Profile Analyses of Locomotor Outcomes Poststroke.

Previous data suggest patient demographics and clinical presentation are primary predictors of motor recovery poststroke, with minimal contributions of physical interventions. Other studies indicate consistent associations between the amount and intensity of stepping practice with locomotor outcomes. The goal of this study was to determine the relative contributions of these combined variables to locomotor outcomes poststroke across a range of patient demographics and baseline function. Data were pooled from 3 separate trials evaluating the efficacy of high-intensity training, low-intensity training, and conventional interventions. Demographics, clinical characteristics, and training activities from 144 participants >1-month poststroke were included in stepwise regression analyses to determine their relative contributions to locomotor outcomes. Subsequent latent profile analyses evaluated differences in classes of participants based on their responses to interventions. Stepwise regressions indicate primary contributions of stepping activity on locomotor outcomes, with additional influences of age, duration poststroke, and baseline function. Latent profile analyses revealed 2 main classes of outcomes, with the largest gains in those who received high-intensity training and achieved the greatest amounts of stepping practice. Regression and latent profile analyses of only high-intensity training participants indicated age, baseline function, and training activities were primary determinants of locomotor gains. Participants with the smallest gains were older (≈60 years), presented with slower gait speeds (<0.40 m/s), and performed 600 to 1000 less steps/session. Regression and cluster analyses reveal primary contributions of training interventions on mobility outcomes in patients >1-month poststroke. Age, duration poststroke, and baseline impairments were secondary predictors. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02507466 and NCT01789853.

Perforin affects regeneration in a mouse spinal cord injury model

Purpose of study: To study the role of the immune response in spinal cord injury, we previously investigated the effects of genetic deletion of functional T- and B-lymphocytes in recombination activating gene 2 (Rag2)-deficient mice. To dissect out another defined and more restricted component of the immune system, we now analyzed mice deficient in perforin, an enzyme with proteolytic activity expressed mainly by natural killer and cytotoxic lymphocytes. Materials and methods Locomotor outcomes in perforin-deficient (Pfp-/-) mice and wild-type littermate controls were measured after severe compression injury of the lower thoracic spinal cord up to six weeks after injury. Results According to both the Basso mouse scale score and single frame motion analysis, motor recovery of Pfp-/- mice was similar to wild-type controls. Interestingly, immunohistochemical analysis of cell types at six weeks after injury showed enhanced cholinergic reinnervation of spinal motor neurons caudal to the lesion site and neurofilament-positive structures at the injury site in Pfp-/- mice, whereas numbers of microglia/macrophages and astrocytes were decreased compared with controls. Conclusions We conclude that, although, loss of perforin does not change the locomotor outcome after injury, it beneficially affects diverse cellular features, such as number of axons, cholinergic synapses, astrocytes and microglia/macrophages at or caudal to the lesion site. Perforin’s ability to contribute to Rag2’s influence on locomotion was observed in mice doubly deficient in perforin and Rag2 which recovered better than Rag2-/- or Pfp-/- mice, suggesting that natural killer cells can cooperate with T- and B-cells in spinal cord injury.

Variability in Open-Field Locomotor Scoring Following Force-Defined Spinal Cord Injury in Rats: Quantification and Implications.

Spinal cord injury research in experimental animals aims to define mechanisms of tissue damage and identify interventions that can be translated into effective clinical therapies. Highly reliable models of injury and outcome measurement are essential to achieve these aims and avoid problems with reproducibility. Functional scoring is a critical component of outcome assessment and is currently commonly focused on open field locomotion (the “BBB score”). Here we analyze variability of observed locomotor outcome after a highly regulated spinal cord contusion in a large group of rats that had not received any therapeutic intervention. Our data indicate that, despite tight regulation of the injury severity, there is considerable variability in open-field score of individual rats at 21 days after injury, when the group as a whole reaches a functional plateau. The bootstrapped reference interval (that defines boundaries that contain 95% scores in the population without regard for data distributional character) for the score at 21 days was calculated to range from 2.3 to 15.9 on the 22-point scale. Further analysis indicated that the mean day 21 score of random groups of 10 individuals drawn by bootstrap sampling from the whole study population varies between 9.5 and 13.5. Wide variability between individuals implies that detection of small magnitude group-level treatment effects will likely be unreliable, especially if using small experimental group sizes. To minimize this problem in intervention studies, consideration should be given to assessing treatment effects by comparing proportions of animals in comparator groups that attain pre-specified criterion scores.

Transplantation of Skin Precursor-Derived Schwann Cells Yields Better Locomotor Outcomes and Reduces Bladder Pathology in Rats with Chronic Spinal Cord Injury.

SummaryCell transplantation for spinal cord injury (SCI) has largely been studied in sub-acute settings within 1–2 weeks of injury. In contrast, here we transplanted skin-derived precursors differentiated into Schwann cells (SKP-SCs) into the contused rat spinal cord 8 weeks post-injury (wpi). Twenty-one weeks later (29 wpi), SKP-SCs were found to have survived transplantation, integrated with host tissue, and mitigated the formation of a dense glial scar. Furthermore, transplanted SKP-SCs filled much of the lesion sites and greatly enhanced the presence of endogenous SCs, which myelinated thousands of sprouting/spared host axons in and around the injury site. In addition, SKP-SC transplantation improved locomotor outcomes and decreased pathological thickening of bladder wall. To date, functional improvements have very rarely been observed with cell transplantation beyond the sub-acute stage of injury. Hence, these findings indicate that skin-derived SCs are a promising candidate cell type for the treatment of chronic SCI.

Task-Specific Versus Impairment-Based Training on Locomotor Performance in Individuals With Chronic Spinal Cord Injury: A Randomized Crossover Study

Background. Many research studies attempting to improve locomotor function following motor incomplete spinal cord injury (iSCI) focus on providing stepping practice. However, observational studies of physical therapy strategies suggest the amount of stepping practice during clinical rehabilitation is limited; rather, many interventions focus on mitigating impairments underlying walking dysfunction. Objective. The purpose of this blinded-assessor randomized trial was to evaluate the effects of task-specific versus impairment-based interventions on walking outcomes in individuals with iSCI. Methods. Using a crossover design, ambulatory participants with iSCI >1-year duration performed either task-specific (upright stepping) or impairment-based training for up to 20 sessions over ≤6 weeks, with interventions alternated after >4 weeks delay. Both strategies focused on achieving higher cardiovascular intensities, with training specificity manipulated by practicing only stepping practice in variable contexts or practicing tasks targeting impairments underlying locomotor dysfunction (strengthening, balance tasks, and recumbent stepping). Results. Significantly greater increases in fastest overground and treadmill walking speeds were observed following task-specific versus impairment-based training, with moderate associations between differences in amount of practice and outcomes. Gains in balance confidence were also observed following task-specific vs impairment-based training, although incidence of falls was also increased with the former protocol. Limited gains were observed with impairment-based training except for peak power during recumbent stepping tests. Conclusion. The present study reinforces work from other patient populations that the specificity of task practice is a critical determinant of locomotor outcomes and suggest impairment-based exercises may not translate to improvements in functional tasks. Clinical Trial Registration URL. https://clinicaltrials.gov/; Unique Identifier: NCT02115685.