A modified rehabilitation paradigm bilaterally increased rat extensor digitorum communis muscle size but did not improve forelimb function after stroke.

Malnutrition after stroke may lessen the beneficial effects of rehabilitation on motor recovery through influences on both brain and skeletal muscle. Enriched rehabilitation (ER), a combination of environmental enrichment and forelimb reaching practice, is used preclinically to study recovery of skilled reaching after stroke. However, the chronic food restriction typically used to motivate engagement in reaching practice is a barrier to using ER to investigate interactions between nutritional status and rehabilitation. Thus, our objectives were to determine if a modified ER program comprised of environmental enrichment and skilled reaching practice motivated by a short fast would enhance post-stroke forelimb motor recovery and preserve forelimb muscle size and metabolic fiber type, relative to a group exposed to stroke without ER. At one week after photothrombotic cortical stroke, male, Sprague-Dawley rats were assigned to modified ER or standard care for 2 weeks. Forelimb recovery was assessed in the Montoya staircase and cylinder task before stroke and on days 5-6, 22-23, and 33-34 after stroke. ER failed to improve forelimb function in either task (p > 0.05). Atrophy of extensor digitorum communis (EDC) and triceps brachii long head (TBL) muscles was not evident in the stroke-targeted forelimb on day 35, but the area occupied by hybrid fibers was increased in the EDC muscle (p = 0.038). ER bilaterally increased EDC (p = 0.046), but not TBL, muscle size; EDC muscle fiber type was unchanged by ER. While the modified ER did not promote forelimb motor recovery, it does appear to have utility for studying the role of skeletal muscle plasticity in post-stroke recovery.

Effects of task-based mirror therapy on upper limb motor function in hemiplegia: study protocol for a randomized controlled clinical trial.

BACKGROUND AND PURPOSE: Research to date has lacked definitive evidence to determine whether mirror therapy promotes the recovery of upper extremity function after stroke. Considering that previous studies did not stratify patients based on structural retention, this may be one of the reasons for the negative results obtained in many trials. The goal evaluates the efficacy of TBMT (utilizing an innovatively designed mirror) versus standard occupational therapy for stroke patient's upper limb functionality. METHODS AND ANALYSIS: This single-center randomized controlled trial will involve 50 patients with stroke. All patients will be randomly assigned to either the task-based mirror therapy or the control group. The interventions will be performed 5 days per week for 4 weeks. The primary outcomes will be the mean change in scores on both the FMA-UE and modified Barthel Index (MBI) from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The other outcomes will include the Action Research Arm Test (ARAT), the Nine Hole Peg Test (9HPT), the Functional Independence Measure, and MRI. DISCUSSION: This trial will not only to establish that task-based mirror therapy (TBMT) could improve the recovery of hand function after stroke but also to explore the underlying mechanisms. We expect that this finding will clarify the brain activation and brain network mechanisms underlying the improvement of hand function with task-oriented mirror therapy and lead to new ideas for stroke hand function rehabilitation. TRIAL REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR2300068855. Registered on March 1, 2023.

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. METHODS: C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. RESULTS: Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3-5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. CONCLUSIONS: Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.

Inhibition of UHRF1 Improves Motor Function in Mice with Spinal Cord Injury.

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.

The effect of early mobilisation (< 14 days) on pathophysiological and functional outcomes in animals with induced spinal cord injury: a systematic review with meta-analysis.

INTRODUCTION: The optimum time to mobilise (standing, walking) following spinal cord injury (SCI) is unknown but may have implications for patient outcomes. There are no high-quality experimental studies that examine this issue, with a paucity of guidance for clinicians. Pre-clinical studies lead research in this field and can contribute to knowledge and support future clinical practice. OBJECTIVE: to evaluate the effect of early compared to no mobilisation on pathophysiological and functional outcomes in animals with induced SCI. METHODS: A systematic review with meta-analysis was conducted by searching pre-clinical literature in MEDLINE (PubMed), Embase (Ovid), Web of Science, OpenGrey, and EThOS (June 2023). Studies were included of any research method giving numerical results comparing pathophysiological and functional outcomes in rats and mice mobilised within 14-days of induced SCI to those that did not mobilise. Data were synthesised using random-effects meta-analyses. The quality of the evidence was assessed using the CAMARADES checklist. The certainty of findings was reported using the GRADE approach. This study is registered on PROSPERO (CRD42023437494). RESULTS: Seventeen studies met the inclusion criteria. Outcomes found that Brain Derived Neurotrophic Factor levels were greater in those that initiated mobilisation within 14-days of SCI compared to the groups that did not. Mobilisation initiated within 14-days of SCI was also associated with statistically significant functional gains: (Basso, Beattie and Bresnahan locomotor rating score (BBB) = 2.13(0-21), CI 1.43, 2.84, Ladder Rung Walking Task = - 12.38(0-100), CI 20.01, - 4.76). Meta-analysis identified the greatest functional gains when mobilisation was initiated within 3 days of SCI (BBB = 3.00, CI 2.31-3.69, p < 0.001), or when delivered at low intensity (BBB = 2.88, CI 2.03-3.70, p < 0.001). Confidence in the findings from this review was low to moderate due to the risk of bias and mixed methodological quality. CONCLUSION: Mobilisation instigated within 14-days of injury, may be an effective way of improving functional outcomes in animal models following SCI, with delays potentially detrimental to recovery. Outcomes from this study support further research in this field to guide future clinical practice.

Deubiquitinase UCHL1 promotes angiogenesis and blood-spinal cord barrier function recovery after spinal cord injury by stabilizing Sox17.

Improving the function of the blood-spinal cord barrier (BSCB) benefits the functional recovery of mice following spinal cord injury (SCI). The death of endothelial cells and disruption of the BSCB at the injury site contribute to secondary damage, and the ubiquitin-proteasome system is involved in regulating protein function. However, little is known about the regulation of deubiquitinated enzymes in endothelial cells and their effect on BSCB function after SCI. We observed that Sox17 is predominantly localized in endothelial cells and is significantly upregulated after SCI and in LPS-treated brain microvascular endothelial cells. In vitro Sox17 knockdown attenuated endothelial cell proliferation, migration, and tube formation, while in vivo Sox17 knockdown inhibited endothelial regeneration and barrier recovery, leading to poor functional recovery after SCI. Conversely, in vivo overexpression of Sox17 promoted angiogenesis and functional recovery after injury. Additionally, immunoprecipitation-mass spectrometry revealed the interaction between the deubiquitinase UCHL1 and Sox17, which stabilized Sox17 and influenced angiogenesis and BSCB repair following injury. By generating UCHL1 conditional knockout mice and conducting rescue experiments, we further validated that the deubiquitinase UCHL1 promotes angiogenesis and restoration of BSCB function after injury by stabilizing Sox17. Collectively, our findings present a novel therapeutic target for treating SCI by revealing a potential mechanism for endothelial cell regeneration and BSCB repair after SCI.

Functional Free Muscle Transfer for Reconstruction of Traumatic Adult Brachial Plexus Injuries.

Traumatic brachial plexus injury is the most common indication for functional free muscle transfer, and elbow flexion recovery is the functional target, followed by shoulder stability and hand reanimation. In this article, we provide a literature review of functional free muscle transfer (FFMT) for adult traumatic brachial plexus injuries and the surgical technical recommendations to achieve the best functional results with FFMT for adult traumatic brachial plexus injuries.

Top-Down and Bottom-Up Mechanisms of Motor Recovery Poststroke.

Stroke remains a leading cause of disability. Motor recovery requires the interaction of top-down and bottom-up mechanisms, which reinforce each other. Injury to the brain initiates a biphasic neuroimmune process, which opens a window for spontaneous recovery during which the brain is particularly sensitive to activity. Physical activity during this sensitive period can lead to rapid recovery by potentiating anti-inflammatory and neuroplastic processes. On the other hand, lack of physical activity can lead to early closure of the sensitive period and downstream changes in muscles, such as sarcopenia, muscle stiffness, and reduced cardiovascular capacity, and blood flow that impede recovery.

Alternate Day Fasting Leads to Improved Post-Stroke Motor Recovery in Mice.

BACKGROUND: Caloric restriction promotes neuroplasticity and recovery after neurological injury. In mice, we tested the hypothesis that caloric restriction can act post-stroke to enhance training-associated motor recovery. METHODS: Mice were trained to perform a skilled prehension task. We then induced a photothrombotic stroke in the caudal forelimb area, after which we retrained animals on the prehension task following an 8-day delay. Mice underwent either ad libitum feeding or alternate day fasting beginning 1-day after stroke and persisting for either 7 days or the entire post-stroke training period until sacrifice. RESULTS: Prior studies have shown that post-stroke recovery of prehension can occur if animals receive rehabilitative training during an early sensitive period but is incomplete if rehabilitative training is delayed. In contrast, we show complete recovery of prehension, despite a delay in rehabilitative training, when mice underwent alternate day fasting beginning 1-day post-stroke and persisting for either 7 days or the entire post-stroke training period until sacrifice. Recovery was independent of weight loss. Stroke volumes were similar across groups. CONCLUSIONS: Post-stroke caloric restriction led to recovery of motor function independent of a protective effect on stroke volume. Prehension recovery improved even after ad libitum feeding was reinstituted suggesting that the observed motor recovery was not merely a motivational response. These data add to the growing evidence that post-stroke caloric restriction can enhance recovery.

Combination of different noninvasive brain stimulation treatments for upper limb recovery in stroke patients: A systematic review.

We report a review of Pubmed (Medline), CENTRAL, Web of Science, and Scopus to test the effectiveness of the combined application of repetitive transcranial magnetic stimulation and transcranial direct current stimulation in the improvement of different functional variables of the upper limb in people with stroke. Two independent reviewers assessed eligibility and evaluated the quality of the studies. Five articles were included in the final review according to the inclusion criteria: Most show statistically significant differences in motor function improvement in favor of the experimental group, but not in activity. Due to the heterogeneity of the observed studies, the results should be interpreted with caution-more high-quality studies are needed to investigate the effectiveness of these interventions in different stages of stroke patients.

Effects of Priming Intermittent Theta Burst Stimulation With High-Definition tDCS on Upper Limb Function in Hemiparetic Patients With Stroke: A Randomized Controlled Study.

BACKGROUND: Preconditioning with cathodal high-definition transcranial direct current stimulation (HD-tDCS) can potentiate cortical plasticity induced by intermittent theta burst stimulation (iTBS) and enhance the after-effects of iTBS in healthy people. However, it is unclear whether this multi-modal protocol can enhance upper limb function in patients with stroke. OBJECTIVE: The aim of this study was to investigate whether priming iTBS with cathodal HD-tDCS over the ipsilesional M1 can augment upper limb motor recovery in poststroke patients. METHODS: A total of 66 patients with subacute stroke were randomly allocated into 3 groups. Group 1 received priming iTBS with HD-tDCS (referred to as the tDCS + iTBS group), Group 2 received non-priming iTBS (the iTBS group), and Group 3 received sham stimulation applied to the ipsilesional M1. One session was performed per day, 5 days per week, for 3 consecutive weeks. In Group 1, iTBS was preceded by a 20-minute session of cathodal HD-tDCS at a 10-minute interval. The primary outcome measure was the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score. Moreover, the secondary outcome measures for muscle strength and spasticity were the Motricity Index-Upper Extremity (MI-UE) and the Modified Ashworth Scale Upper-Extremity (MAS-UE), respectively, and the Hong Kong Version of the Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK) and the Modified Barthel Index (MBI) for activity and participation. RESULTS: Significant differences were detected in the changes in FMA-UE, MI-UE, and MBI scores between the 3 groups from baseline to post-intervention (χ2FMA-UE = 10.856, P = .004; χ2MI-UE = 6.783, P = .034; χ2MBI = 9.608, P = .008). Post hoc comparisons revealed that the priming iTBS group demonstrated substantial improvements in FMA-UE (P = .004), MI-UE (P = .028), and MBI (P = 0.006) compared with those in the sham group. However, no significant difference was observed between the iTBS group and the sham group. Moreover, no significant differences were found in the changes in MAS-UE or FTHUE-HK between the groups. CONCLUSIONS: Priming iTBS with HD-tDCS over the ipsilesional M1 cortex had beneficial effects on augmenting upper limb motor recovery and enhancing daily participation among subacute stroke patients.

Brain Plasticity in Patients with Spinal Cord Injuries: A Systematic Review.

A spinal cord injury (SCI) causes changes in brain structure and brain function due to the direct effects of nerve damage, secondary mechanisms, and long-term effects of the injury, such as paralysis and neuropathic pain (NP). Recovery takes place over weeks to months, which is a time frame well beyond the duration of spinal shock and is the phase in which the spinal cord remains unstimulated below the level of injury and is associated with adaptations occurring throughout the nervous system, often referred to as neuronal plasticity. Such changes occur at different anatomical sites and also at different physiological and molecular biological levels. This review aims to investigate brain plasticity in patients with SCIs and its influence on the rehabilitation process. Studies were identified from an online search of the PubMed, Web of Science, and Scopus databases. Studies published between 2013 and 2023 were selected. This review has been registered on OSF under (n) 9QP45. We found that neuroplasticity can affect the sensory-motor network, and different protocols or rehabilitation interventions can activate this process in different ways. Exercise rehabilitation training in humans with SCIs can elicit white matter plasticity in the form of increased myelin water content. This review has demonstrated that SCI patients may experience plastic changes either spontaneously or as a result of specific neurorehabilitation training, which may lead to positive outcomes in functional recovery. Clinical and experimental evidence convincingly displays that plasticity occurs in the adult CNS through a variety of events following traumatic or non-traumatic SCI. Furthermore, efficacy-based, pharmacological, and genetic approaches, alone or in combination, are increasingly effective in promoting plasticity.

Serum response factor promoting axonal regeneration by activating the Ras-Raf-Cofilin signaling pathway after the spinal cord injury.

INTRODUCTION: Serum response factor (SRF) is important in muscle development, tissue repair, and neuronal regulation. OBJECTIVES: This research aims to thoroughly examine the effects of SRF on spinal cord injury (SCI) and its ability to significantly impact the recovery and regeneration of neuronal axons. METHODS: The researchers created rat models of SCI and scratch injury to primary spinal cord neurons to observe the expression of relevant factors after neuronal injury. RESULTS: We found that the SRF, Ras, Raf, and cofilin levels increased after injury and gradually returned to normal levels. Afterward, researchers gave rats with SCI an SRF inhibitor (CCG1423) and studied the effects with nuclear magnetic resonance and transmission electron microscopy. The SRF inhibitor rodents had worse spinal cord recovery and axon regrowth than the control group. And the apoptosis of primary neurons after scratch injury was significantly higher in the SRF inhibitor group. Additionally, the researchers utilized lentiviral transfection to modify the SRF expression in neurons. SRF overexpression increased neuron migration while silencing SRF decreased it. Finally, Western blotting and RT-PCR were conducted to examine the expression changes of related factors upon altering SRF expression. The results revealed SRF overexpression increased Ras, Raf, and cofilin expression. Silencing SRF decreased Ras, Raf, and Cofilin expression. CONCLUSION: Based on our research, the SRF promotes axonal regeneration by activating the "Ras-Raf-Cofilin" signaling pathway.

AAV-mediated VEGFA overexpression promotes angiogenesis and recovery of locomotor function following spinal cord injury via PI3K/Akt signaling.

Spinal cord injury (SCI) is a disorder of the central nervous system resulting from various factors such as trauma, inflammation, tumors, and other etiologies. This condition leads to impairment in motor, sensory, and autonomic functions below the level of injury. Limitations of current therapeutic approaches prompt an investigation into therapeutic angiogenesis through persistent local expression of proangiogenic factors. Here, we investigated whether overexpression of adeno-associated virus (AAV)-mediated vascular endothelial growth factor A (VEGFA) in mouse SCI promoted locomotor function recovery, and whether the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was mechanistically involved. Three weeks before SCI, AAV-VEGFA was injected at the T10 level to induce VEGFA overexpression. Neurofunctional, histological, and biochemical assessments were done to determine tissue damage and/or recovery of neuromuscular and behavioral impairments. Daily injections of the PI3K/Akt pathway inhibitor LY294002 were made to assess a possible mechanism. AAV-VEGFA overexpression dramatically improved locomotor function and ameliorated pathological injury caused by SCI. Improved motor-evoked potentials in hindlimbs and more spinal CD31-positive microvessels were observed in AAV-VEGFA-overexpressing mice. LY294002 reduced PI3K and Akt phosphorylation levels and attenuated AAV-VEGFA-related improvements. In conclusion, sustained local AAV-mediated VEGFA overexpression in spinal cord can significantly promote angiogenesis and ameliorate locomotor impairment after SCI in a contusion mouse model through activation of the PI3K/Akt signaling pathway.

Tlr4 Deletion Modulates Cytokine and Extracellular Matrix Expression in Chronic Spinal Cord Injury, Leading to Improved Secondary Damage and Functional Recovery.

Toll-like receptors (TLRs) play an important role in the innate immune response after CNS injury. Although TLR4 is one of the best characterized, its role in chronic stages after spinal cord injury (SCI) is not well understood. We examined the role of TLR4 signaling in injury-induced responses at 1 d, 7 d, and 8 weeks after spinal cord contusion injury in adult female TLR4 null and wild-type mice. Analyses include secondary damage, a range of transcriptome and protein analyses of inflammatory, cell death, and extracellular matrix (ECM) molecules, as well as immune cell infiltration and changes in axonal sprouting and locomotor recovery. Lack of TLR4 signaling results in reduced neuronal and myelin loss, reduced activation of NFκB, and decreased expression of inflammatory cytokines and necroptotic cell death pathway at a late time point (8 weeks) after injury. TLR4 null mice also showed reduction of scar-related ECM molecules at 8 weeks after SCI, accompanied by increase in ECM molecules associated with perineuronal nets, increased sprouting of serotonergic fibers, and improved locomotor recovery. These findings reveal novel effects of TLR4 signaling in chronic SCI. We show that TLR4 influences inflammation, cell death, and ECM deposition at late-stage post-injury when secondary injury processes are normally considered to be over. This highlights the potential for late-stage targeting of TLR4 as a potential therapy for chronic SCI.

Sleep and motor learning in stroke (SMiLES): a longitudinal study investigating sleep-dependent consolidation of motor sequence learning in the context of recovery after stroke.

INTRODUCTION: There is growing evidence that sleep is disrupted after stroke, with worse sleep relating to poorer motor outcomes. It is also widely acknowledged that consolidation of motor learning, a critical component of poststroke recovery, is sleep-dependent. However, whether the relationship between disrupted sleep and poor outcomes after stroke is related to direct interference of sleep-dependent motor consolidation processes, is currently unknown. Therefore, the aim of the present study is to understand whether measures of motor consolidation mediate the relationship between sleep and clinical motor outcomes post stroke. METHODS AND ANALYSIS: We will conduct a longitudinal observational study of up to 150 participants diagnosed with stroke affecting the upper limb. Participants will be recruited and assessed within 7 days of their stroke and followed up at approximately 1 and 6 months. The primary objective of the study is to determine whether sleep in the subacute phase of recovery explains the variability in upper limb motor outcomes after stroke (over and above predicted recovery potential from the Predict Recovery Potential algorithm) and whether this relationship is dependent on consolidation of motor learning. We will also test whether motor consolidation mediates the relationship between sleep and whole-body clinical motor outcomes, whether motor consolidation is associated with specific electrophysiological sleep signals and sleep alterations during subacute recovery. ETHICS AND DISSEMINATION: This trial has received both Health Research Authority, Health and Care Research Wales and National Research Ethics Service approval (IRAS: 304135; REC: 22/LO/0353). The results of this trial will help to enhance our understanding of the role of sleep in recovery of motor function after stroke and will be disseminated via presentations at scientific conferences, peer-reviewed publication, public engagement events, stakeholder organisations and other forms of media where appropriate. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05746260, registered on 27 February 2023.

Osteopontin Promotes Angiogenesis in the Spinal Cord and Exerts a Protective Role Against Motor Function Impairment and Neuropathic Pain After Spinal Cord Injury.

STUDY DESIGN: Basic science study using a hemisection spinal cord injury (SCI) model. OBJECTIVE: We sought to assess the effect of blocking osteopontin (OPN) upregulation on motor function recovery and pain behavior after SCI and to further investigate the possible downstream target of OPN in the injured spinal cord. SUMMARY OF BACKGROUND DATA: OPN is a noncollagenous extracellular matrix protein widely expressed across different tissues. Its expression substantially increases following SCI. A previous study suggested that this protein might contribute to locomotor function recovery after SCI. However, its neuroprotective potential was not fully explored, nor were the underlying mechanisms. MATERIALS AND METHODS: We constructed a SCI mouse model and analyzed the expression of OPN at different time points and the particular cell distribution in the injured spinal cord. Then, we blocked OPN upregulation with lentivirus-delivering siRNA targeting OPN specifically and examined its effect on motor function impairment and neuropathic pain after SCI. The underlying mechanisms were explored in the OPN-knockdown mice model and cultured vascular endothelial cells. RESULTS: The proteome study revealed that OPN was the most dramatically increased protein following SCI. OPN in the spinal cord was significantly increased three weeks after SCI. Suppressing OPN upregulation through siRNA exacerbated motor function impairment and neuropathic pain. In addition, SCI resulted in an increase in vascular endothelial growth factor (VEGF), AKT phosphorylation, and angiogenesis within the spinal cord, all of which were curbed by OPN reduction. Similarly, OPN knockdown suppressed VEGF expression, AKT phosphorylation, cell migration, invasion, and angiogenesis in cultured vascular endothelial cells. CONCLUSION: OPN demonstrates a protective influence against motor function impairment and neuropathic pain following SCI. This phenomenon may result from the proangiogenetic effect of OPN, possibly due to activation of the VEGF and/or AKT pathways.

Detection of Rehabilitation Training Effect of Upper Limb Movement Disorder Based on MPL-CNN.

Stroke represents a medical emergency and can lead to the development of movement disorders such as abnormal muscle tone, limited range of motion, or abnormalities in coordination and balance. In order to help stroke patients recover as soon as possible, rehabilitation training methods employ various movement modes such as ordinary movements and joint reactions to induce active reactions in the limbs and gradually restore normal functions. Rehabilitation effect evaluation can help physicians understand the rehabilitation needs of different patients, determine effective treatment methods and strategies, and improve treatment efficiency. In order to achieve real-time and accuracy of action detection, this article uses Mediapipe's action detection algorithm and proposes a model based on MPL-CNN. Mediapipe can be used to identify key point features of the patient's upper limbs and simultaneously identify key point features of the hand. In order to detect the effect of rehabilitation training for upper limb movement disorders, LSTM and CNN are combined to form a new LSTM-CNN model, which is used to identify the action features of upper limb rehabilitation training extracted by Medipipe. The MPL-CNN model can effectively identify the accuracy of rehabilitation movements during upper limb rehabilitation training for stroke patients. In order to ensure the scientific validity and unified standards of rehabilitation training movements, this article employs the postures in the Fugl-Meyer Upper Limb Rehabilitation Training Functional Assessment Form (FMA) and establishes an FMA upper limb rehabilitation data set for experimental verification. Experimental results show that in each stage of the Fugl-Meyer upper limb rehabilitation training evaluation effect detection, the MPL-CNN-based method's recognition accuracy of upper limb rehabilitation training actions reached 95%. At the same time, the average accuracy rate of various upper limb rehabilitation training actions reaches 97.54%. This shows that the model is highly robust across different action categories and proves that the MPL-CNN model is an effective and feasible solution. This method based on MPL-CNN can provide a high-precision detection method for the evaluation of rehabilitation effects of upper limb movement disorders after stroke, helping clinicians in evaluating the patient's rehabilitation progress and adjusting the rehabilitation plan based on the evaluation results. This will help improve the personalization and precision of rehabilitation treatment and promote patient recovery.

GPNMB Modulates Autophagy to Enhance Functional Recovery After Spinal Cord Injury in Rats.

Spinal cord injury (SCI) severely affects the quality of life and autonomy of patients, and effective treatments are currently lacking. Autophagy, an essential cellular metabolic process, plays a crucial role in neuroprotection and repair after SCI. Glycoprotein non-metastatic melanoma protein B (GPNMB) has been shown to promote neural regeneration and synapse reconstruction, potentially through the facilitation of autophagy. However, the specific role of GPNMB in autophagy after SCI is still unclear. In this study, we utilized the spinal cord transection method to establish SCI rats model and overexpressed GPNMB using adenoviral vectors. We assessed tissue damage using hematoxylin and eosin (H&E) and Nissl staining, and observed cell apoptosis using TUNEL staining. We evaluated the inflammatory response by measuring inflammatory factors using enzyme-linked immunosorbent assay (ELISA). In addition, we measured reactive oxygen species (ROS) levels using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and assessed oxidative stress levels by measuring malondialdehyde (MDA) and glutathione (GSH) using ELISA. To evaluate autophagy levels, we performed immunofluorescence staining for the autophagy marker Beclin-1 and conducted Western blot analysis for autophagy-related proteins. We also assessed limb recovery through functional evaluation. Meanwhile, we induced cell injury using lipopolysaccharide (LPS) and added an autophagy inhibitor to verify the impact of GPNMB on SCI through autophagy modulation. The results demonstrated that GPNMB alleviated the inflammatory response, reduced oxidative stress levels, inhibited cell apoptosis, and promoted autophagy following SCI. Inhibiting autophagy reversed the effects of GPNMB. These findings suggest that GPNMB promotes neural injury repair after SCI, potentially through attenuating the inflammatory response, reducing oxidative stress, and inhibiting cell apoptosis.

Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury.

The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an ex vivo gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, ex vivo gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI.