Neurorehabilitation and neural repair最新文献

Background: In humans, most spontaneous recovery from motor impairment after stroke occurs in the first 3 months. Studies in animal models show higher responsiveness to training over a similar time-period. Both phenomena are often attributed to a milieu of heightened plasticity, which may share some mechanistic overlap with plasticity associated with normal motor learning.

Objective: Given that neurorehabilitation approaches are frequently predicated on motor learning principles, here we asked if the sensitivity of trial-to-trial learning for 2 kinds of motor learning processes often involved during rehabilitation is also enhanced early post-stroke. In a cross-sectional design, we compared (1) reinforcement and (2) error-based learning in 2 groups: 1 tested within 3 months after stroke (early group, N = 35) another tested more than 6 months after stroke (late group, N = 30). These 2 forms of motor learning were assessed with variations of the same visuomotor rotation task. Critically, motor execution was matched between the 2 groups.

Results: Reinforcement learning was impaired in the early but not the late group, whereas error-based learning was unimpaired in either group. These findings could not be attributed to differences in baseline execution, cognitive impairment, gender, age, or lesion volume and location.

Discussion: The presence of a deficit in reinforcement motor learning in the first 3 months after stroke has important implications for rehabilitation.

Conclusion: It might be necessary to either increase reinforcement feedback given early after stroke, increase the dose of rehabilitation to compensate, or delay onset of rehabilitation approaches that may rely on reinforcement, for example, constraint-induced movement therapy, and instead emphasize other forms of motor training in the subacute time period.

Background: There is a critical time window of post-stroke neuroplasticity when spontaneous behavioral recovery occurs. Potential factors responsible for this heightened plasticity are the reduction of parvalbumin-immunoreactive (PV+) interneuron inhibitory signaling and the disappearance of extracellular matrix synaptic stabilizers called perineuronal net(s; PNN/PNNs).

Objective: This study investigated whether behavioral recovery during this critical period following stroke is associated with changes in densities of PV+ interneurons and PNNs.

Methods: Male, Sprague-Dawley rats received forelimb motor cortex stroke (n = 43) using endothelin-1, or vehicle injections (n = 44). Cohorts of rats underwent a battery of motor tests and were sacrificed within the post-stroke critical window on day 1, and 1, 2, 4, and 6 weeks. Using immunofluorescent labeling, PNNs (wisteria floribunda agglutinin; WFA+ cells), PV+ interneurons, and cells expressing both PV and PNNs were quantified in contra- and ipsilesional cortices to elucidate their spatial-temporal profiles following stroke.

Results: PV+ interneuron density decreased significantly at 1-day post-stroke in the lateral ipsilesional cortex, while the density of PNNs was significantly lower up to 4 weeks post-stroke in the lateral ipsilesional cortex and at 1 and 2 weeks post-stroke in the medial ipsilesional cortex. Reduction of combined PV+/PNN signaling coincided with spontaneous behavioral recovery.

Conclusions: These results suggest that post-stroke behavioral recovery corresponds to an early reduction in PV+/PNN co-labeled cells in conjunction with an early temporally-dependent reduction in PV+ interneuron signaling and chronic disappearance of PNNs. Interventions targeting PNNs or PV+ interneuron signaling have significant potential for extending the critical window of recovery following stroke.

Background: How gait changes during the early stages of stoke rehabilitation, and which patient characteristics are associated with these changes is still largely unknown.

Objective: he first objective was to describe the changes in gait during stroke rehabilitation. Secondly, we determined how various patient characteristics were associated with the rate of change of gait over time.

Methods: Participants were measured every 3 weeks during stroke rehabilitation. The assessment consisted of an inertial measurement unit (IMU) based 2-minute walk test (2MWT), 3 IMU-based balance tests, and standard clinical tests. In the 2MWT, participants were equipped with 3 IMUs, from which speed, variability, asymmetry, and smoothness were calculated. The changes in gait were examined from admission to discharge at an individual level. The effect of patient characteristics on the rate of change of the gait features over time was assessed with growth models.

Results: A total of 81 Trajectories from 72 participants were analyzed. On an individual basis, speed increased in 32 trajectories. Only a few trajectories exhibited significant changes in variability, asymmetry, and smoothness over the clinical rehabilitation period. The growth models revealed a significant increase in speed and decrease in variability and smoothness. Only the Berg Balance Scale and gait speed at onset were (negatively) associated with the rates of change of speed and smoothness, respectively.

Conclusion: We found a substantial variability in the gait-feature outcomes and their progression in individuals after stroke during clinical rehabilitation. The patient characteristics studied had limited associations with the rate of change of gait features over time.

Background. Non-invasive brain stimulation (NIBS) is sometimes used alongside medication to alleviate motor symptoms in people with Parkinson's disease (PD). However, the evidence supporting NIBS's effectiveness for improving motor function in PD patients is uncertain. Objective. This umbrella review aims to synthesize recent systematic reviews and meta-analyses that have evaluated the effectiveness of NIBS in improving motor function in people with PD, with a key focus being to examine the quality of the evidence presented. Methods. The review protocol was registered in PROSPERO (CRD42022380544) and conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search strategy was guided by the Population, Intervention, Comparison, and Outcome framework, focusing on individuals with idiopathic PD (Hoehn and Yahr stages 1-4). The review included studies comparing various NIBS techniques (eg, repetitive transcranial magnetic stimulation and transcranial direct current stimulation) to sham or alternative treatments, targeting motor and cognitive regions. Six databases were searched up to June 2024. Methodological quality was assessed using Assessment of Multiple Systematic Reviews 2 (AMSTAR2), and random-effects meta-analyses were performed to pool standardized mean differences (SMDs). Results. The final analysis included 31 meta-analyses and 10 systematic reviews. Overall, the reviews were rated as moderate quality (54% average for AMSTAR2). NIBS showed a small-to-moderate effect on motor function (Unified Parkinson's Disease Rating Scale-Section III scores; SMD = -0.80), functional mobility (gait speed and timed-up-and-go; SMD = -0.39), and freezing of gait (SMD = -0.58), but no significant effect on balance. Conclusion. NIBS offers small-to-moderate benefits for motor symptoms and functional movement in PD, though it does not significantly impact balance. Practitioners should consider the variety of techniques and treatment parameters before application.

Background: Spinal cord injury (SCI) can impair motor, sensory, and autonomic function. The formation of the glial scar comprises protective as well as inhibitory neurite outgrowth properties operated by the deposition of chondroitin sulfate proteoglycans (CSPG). Chondroitinase ABC (ChABC) can degrade CSPG and foster neuroaxonal plasticity as a therapeutic approach to restore locomotor function after SCI.

Objectives: To systematically review experimental ChABC treatments after SCI and assess their efficacy for locomotor function a comprehensive literature search was conducted following pre-registered Prospero Study protocol, selecting animal studies evaluating neurobehavioral outcomes after traumatic SCI followed by the calculation of normalized effect sizes applying meta-analysis and meta-regression methodology. Additional analyses were performed to investigate the impact of animal type, strain, sex, sample size, injury models, level of injury, and treatment duration.

Results: Within the overall analysis of 1066 animals, a considerable amount of heterogeneity was observed. A subgroup analysis comprising experiments applying the same neurobehavioral measurement (blood-brain barrier/Basso-Mouse-Scale [BMS]-subgroup) demonstrated a 15.9% (95% CI = 11.3%-20.6%) improvement in locomotor outcomes. Different experimental characteristics influenced neurological recovery, including sex, level of injury, used anesthetic, reported dosage of ChABC treatment, the timepoint of assessment and perioperative temperature control. Sensitivity analysis applying Trim and Fill identified 19 hypothetical missing experiments suggestive of reporting bias.

Conclusion: Reporting bias in experimental SCI research is prevalent and not limited to a specific intervention. ChABC treatment can exert beneficial effects on locomotor recovery after SCI.

Background: Postural instability is a common observation after concussions, with balance assessments playing a crucial role in clinical evaluations. Widely used post-concussion balance tests focus primarily on static and dynamic balance, excluding the critical aspect of reactive balance.

Objectives: This study investigated the acute and longitudinal effects of concussion on reactive balance in collegiate athletes.

Methods: Concussed and healthy matched controls NCAA division I athletes were assessed at pre-season baseline and 4 post-concussion timepoints: acute, pre-return-to-play (RTP), post-RTP, and 6 months post-concussion. The instrumented-modified Push and Release test measured reactive balance during single- and dual-task conditions. Longitudinal effects of concussions on time to stability and step latency metrics were investigated applying Generalized Estimating Equations.

Results: Acutely after concussion, athletes demonstrated impaired reactive balance, indicated by longer times to stability, in dual-task conditions (P = .004). These acute impairments were transient and recovered over time. Exploratory analyses revealed that athletes who sustained their first lifetime concussion exhibited both acute (P = .037) and longitudinal (P = .004 at post-RTP) impairments in single- and dual-task compared to controls with no lifetime concussion.

Conclusions: This comprehensive evaluation provides insights into the multifaceted nature of post-concussion impairments and emphasizes the importance of considering cognitive demand and history of concussions in assessing athletes' balance.

Background and objective: The metaverse refers to a digital realm accessible via internet connections using virtual reality and augmented reality glasses for promoting a new era of social rehabilitation. It represents the next-generation mobile computing platform expected to see widespread utilization in the future. In the context of rehabilitation, the metaverse is envisioned as a novel approach to enhance the treatment of human functioning exploiting the "synchronized brains" potential exacerbated by social interactions in virtual scenarios.

Results: The metaverse emerges as an ideal domain for adapting the principles of the-International Classification of Functioning. Its intrinsic capacity to simulate interactions within virtual environments shared by multi-users, while providing a profound sense of presence and comprehensive perception, should facilitate learning and experiential understanding. Technical and conceptual aspects are currently under definition, including the interplay with artificial intelligence, definition of social metrics performance, and the utilization of blockchain technology for economic purposes.

Conclusion: Building upon these foundations, this paper explores potential areas of metaverse applications in rehabilitation and examines how they may facilitate the pillars outlined in the World Health Organization's Rehabilitation 2030 call for action.

Background: While it is evident that stroke impairs motor control, it remains unclear whether stroke impacts motor adaptation-the ability to flexibly modify movements in response to changes in the body and the environment. The mixed results in the literature may be due to differences in participants' brain lesions, sensorimotor tasks, or a combination of both.

Objective: We first sought to better understand the overall impact of stroke on motor adaptation and then to delineate the impact of lesion hemisphere and sensorimotor task on adaptation poststroke.

Methods: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, we conducted a systematic review and meta-analysis of 18 studies comparing individuals poststroke to neurotypical controls, with each group consisting of over 200 participants.

Results: We found that stroke impairs motor adaptation (d = -0.63; 95% confidence interval [-1.02, -0.24]), and that the extent of this impairment did not differ across sensorimotor tasks but may vary with the lesioned hemisphere. Specifically, we observed greater evidence for impaired adaptation in individuals with left hemisphere lesions compared to those with right hemisphere lesions.

Conclusions: This review not only clarifies the detrimental effect of stroke on motor adaptation but also underscores the need for finer-grained studies to determine precisely how various sensorimotor learning mechanisms are impacted. The current findings may guide future mechanistic and applied research at the intersection of motor learning and neurorehabilitation.

Background: Unilateral hemispheric stroke can impair the ipsilesional motor performance, which is crucial for attaining optimal functional outcomes poststroke. However, the specific brain structures contributing to ipsilesional motor performance impairment remain unclear.

Objective: To explore the link between ipsilesional motor performance and the microstructural integrity of relevant neural pathways.

Methods: This study enrolled 60 consecutive patients in the early subacute phase of stroke recovery. Ipsilesional motor performance was assessed using the Box and Block Test. Multiple linear regression was used to evaluate the associations between ipsilesional motor performance and the microstructural integrity of relevant white matter tracts (Biomarker models) and cognitive function test scores (Cognition models).

Results: Biomarker models, including the genu of the corpus callosum, ipsilesional cingulum, fornix, uncinate fasciculus, superior longitudinal fasciculus, and contralesional inferior longitudinal fasciculus, showed a significant association with ipsilesional motor performance. Cognition models, including Mini-Mental State Examination and Trail Making Test-B, were significantly associated with ipsilesional motor performance. Final regression models (combined Cognition and Biomarker models) revealed that the performance time of Trail Making Test-B, in combination with biomarkers, including the genu of the corpus callosum, ipsilesional superior longitudinal fasciculus, and ipsilesional cingulum, predicted ipsilesional motor performance with high explanatory power (adjusted R² = .721, .709, and .696, respectively).

Conclusions: This study demonstrated that executive function is associated with poststroke ipsilesional motor performance, as evidenced by the microstructural biomarkers involved in executive function. Our findings highlight that the comprehensive role of cognitive functioning rather than the motor system is closely linked to poststroke ipsilesional motor performance.

Background: The peripheral nervous system (PNS) exhibits remarkable regenerative capability after injury. PNS regeneration relies on neurons themselves as well as a variety of other cell types, including Schwann cells, immune cells, and non-neuronal cells.

Objectives: This paper focuses on summarizing the critical roles of immune cells (SCs) in the injury and repair processes of the PNS.

Results: During peripheral nerve injury, macrophages infiltrate the site under the induction of various cytokines, primarily accumulating at the dorsal root ganglia (DRG) and the nerve distal to the injury site, with only a small number detected at the nerve proximal to the injury site. The phenotype of macrophages during injury remains controversial, but recent single-cell sequencing analyses may provide new insights. In peripheral nervous system injury, macrophages participate in Wallerian degeneration as well as in the reconstruction of nerve bridges and angiogenesis during axonal regeneration. Neutrophils appear early in the injury process and are primarily present at the injury site and the distal segment. After peripheral nervous system injury, immature neutrophils from the peripheral blood play a major role. Although lymphocytes constitute only a small fraction compared to macrophages and neutrophils after peripheral nervous system injury, they still play important roles, including Treg cells, B cells, and NK cells. A large number of immune cells accumulate at the injury site, contributing not only to Wallerian degeneration but also to axonal regeneration.

Conclusion: In conclusion, this paper summarizes current knowledge regarding the mechanisms of immune cell infiltration after PNS injury, providing new insights for future research on the role of immune cells in peripheral nerve injury.