Background: Upper limb dysfunction after stroke seriously affects quality of life. Bilateral training has proven helpful in recovery of upper limb motor function in these patients. However, studies evaluating the effectiveness of bilateral upper limb robot-assisted training on improving motor function and quality of life in stroke patients are lacking. Quantitative electroencephalography (EEG) is non-invasive, simple, and monitors cerebral cortical activity, which can be used to evaluate the effectiveness of interventions. In this study, EEG was used to evaluate the effect of end-drive bilateral upper extremity robot-assisted training on upper extremity functional recovery in stroke patients. Methods: 24 stroke patients with hemiplegia were randomly divided into a conventional training (CT, n = 12) group or a bilateral upper limb robot-assisted training (BRT, n = 12) group. All patients received 60 min of routine rehabilitation treatment including rolling, transferring, sitting, standing, walking, etc., per day, 6 days a week, for three consecutive weeks. The BRT group added 30 min of bilateral upper limb robot-assisted training per day, while the CT group added 30 min of upper limb training (routine occupational therapy) per day, 6 days a week, for 3 weeks. The primary outcome index to evaluate upper limb motor function was the Fugl-Meyer functional score upper limb component (FMA-UE), with the secondary outcome of activities of daily living (ADL), assessed by the modified Barthel index (MBI) score. Quantitative EEG was used to evaluate functional brain connectivity as well as alpha and beta power current source densities of the brain. Results: Significant (p < 0.05) within-group differences were found in FMA-UE and MBI scores for both groups after treatment. A between-group comparison indicated the MBI score of the BRT group was significantly different from that of the CT group, whereas the FMA-UE score was not significantly different from that of the CT group after treatment. The differences of FMA-UE and MBI scores before and after treatment in the BRT group were significantly different as compared to the CT group. In addition, beta rhythm power spectrum energy was higher in the BRT group than in the CT group after treatment. Functional connectivity in the BRT group, under alpha and beta rhythms, was significantly increased in both the bilateral frontal and limbic lobes as compared to the CT group. Conclusions: BRT outperformed CT in improving ADL in stroke patients within three months, and BRT facilitates the recovery of upper limb function by enhancing functional connectivity of the bilateral cerebral hemispheres.

Background: Stroke is the second leading cause of death and the third leading cause of disability worldwide, with ischemic stroke (IS) being the most prevalent. A substantial number of irreversible brain cell death occur in the short term, leading to impairment or death in IS. Limiting the loss of brain cells is the primary therapy target and a significant clinical issue for IS therapy. Our study aims to establish the gender specificity pattern from immune cell infiltration and four kinds of cell-death perspectives to improve IS diagnosis and therapy.Methods: Combining and standardizing two IS datasets (GSE16561 and GSE22255) from the GEO database, we used the CIBERSORT algorithm to investigate and compare the immune cell infiltration in different groups and genders. Then, ferroptosis-related differently expressed genes (FRDEGs), pyroptosis-related DEGs (PRDEGs), anoikis-related DEGs (ARDEGs), and cuproptosis-related DEGs (CRDEGs) between the IS patient group and the healthy control group were identified in men and women, respectively. Machine learning (ML) was finally used to generate the disease prediction model for cell death-related DEGs (CDRDEGs) and to screen biomarkers related to cell death involved in IS.Results: Significant changes were observed in 4 types of immune cells in male IS patients and 10 types in female IS patients compared with healthy controls. In total, 10 FRDEGs, 11 PRDEGs, 3 ARDEGs, and 1 CRDEG were present in male IS patients, while 6 FRDEGs, 16 PRDEGs, 4 ARDEGs, and 1 CRDEG existed in female IS patients. ML techniques indicated that the best diagnostic model for both male and female patients was the support vector machine (SVM) for CDRDEG genes. SVM’s feature importance analysis demonstrated that SLC2A3, MMP9, C5AR1, ACSL1, and NLRP3 were the top five feature-important CDRDEGs in male IS patients. Meanwhile, the PDK4, SCL40A1, FAR1, CD163, and CD96 displayed their overwhelming influence on female IS patients.Conclusion: These findings contribute to a better knowledge of immune cell infiltration and their corresponding molecular mechanisms of cell death and offer distinct clinically relevant biological targets for IS patients of different genders.

Background: Stroke is a disease with a high fatality rate worldwide and a major cause of long-term disability. In the rehabilitation of limb motor function after stroke, the rehabilitation of upper limb function takes a long time and the recovery progress is slow, which seriously affects the patients’ self-care ability in daily life. Repeated transcranial magnetic stimulation (rTMS) has been increasingly used to improve limb dysfunction in patients with stroke. However, a standardized reference for selecting a magnetic stimulation regimen is not available. Whether to increase the inhibition of the contralateral hemispheric motor cortex remains controversial. This study has evaluated the effects of different rTMS stimulation programs on upper limb function and corresponding brain functional network characteristics of patients with stroke and sought a new objective standard based on changes in brain network parameters to guide accurate rTMS stimulation programs.Method: Thirty-six patients with stroke were selected and divided into control group and treatment group by number table method, with 18 patients in each group, and 3 patients in the control group were turned out and lost due to changes in disease condition. The treatment group was divided into two groups. TMS1 group was given 1 Hz magnetic stimulation in the M1 region of the contralesional hemisphere +10 Hz magnetic stimulation in the M1 region of the affected hemisphere, and the TMS2 group was given 10 Hz magnetic stimulation in the M1 region of the affected hemisphere. The control group was given false stimulation. The treatment course was once a day for 5 days a week for 4 weeks. The Fugl-Meyer Assessment for upper extremity (FMA-UE) sand near-infrared brain function were collected before treatment, 2 weeks after treatment, and 4 weeks after treatment, and the brain function network was constructed. Changes in brain oxygenated hemoglobin concentration and brain network parameters were analyzed with the recovery of motor function (i.e., increased FMA score). Meanwhile, according to the average increment of brain network parameters, the rTMS stimulation group was divided into two groups with good efficacy and poor efficacy. Network parameters of the two groups before and after rTMS treatment were analyzed statistically.Results: (1) Before treatment, there was no statistical difference in Fugl-Meyer score between the control group and the magnetic stimulation group (p = 0.178).Compared with before treatment, Fugl-Meyer scores of 2 and 4 weeks after treatment were significantly increased in both groups (p <0.001), and FMA scores of 4 weeks after treatment were significantly improved compared with 2 weeks after treatment (p < 0.001). FMA scores increased faster in the magnetic stimulation group at 2 and 4 weeks compared with the control group at the same time point (p <0.001).TMS1 and TMS2 were compared at the same time point, FMA score in TMS2 group increased more significantly after 4 weeks of treatment (p = 0.010). (2) Before treatment, HbO2 content in healthy sensory motor cortex (SMC) area of magnetic stimulation group and control group was higher than that in other region of interest (ROI) area, but there was no significant difference in ROI between the two groups. After 4 weeks of treatment, the HbO2 content in the healthy SMC area was significantly decreased (p < 0.001), while the HbO2 content in the affected SMC area was significantly increased, and the change was more significant in the magnetic stimulation group (p < 0.001). (3) In-depth study found that with the recovery of motor function (FMA upper limb score increase ≥4 points) after magnetic stimulation intervention, brain network parameters were significantly improved. The mean increment of network parameters in TMS1 group and TMS2 group was significantly different (χ² = 5.844, p = 0.016). TMS2 group was more advantageous than TMS1 group in improving the mean increment of brain network parameters.Conclusion: (1) The rTMS treatment is beneficial to the recovery of upper limb motor function in stroke patients, and can significantly improve the intensity of brain network connection and reduce the island area. The island area refers to an isolated activated brain area that cannot transmit excitation to other related brain areas. (2) When the node degree of M1_Healthy region less than 0.52, it is suggested to perform promotion therapy only in the affected hemisphere. While the node degree greater than 0.52, and much larger than that in the M1_affected region. it is suggested that both inhibition in the contralesional hemisphere and high-frequency excitatory magnetic stimulation in the affected hemisphere can be performed. (3) In different brain functional network connection states, corresponding adjustment should be made to the treatment plan of rTMS to achieve optimal therapeutic effect and precise rehabilitation treatment.

Objective: To evaluate if bilateral or unilateral upper limb robot-assisted rehabilitation training using a new three-dimensional end-effector robot that targets shoulder and elbow flexion and abduction is superior to conventional therapy with regard to upper extremity motor function recovery and neuromuscular improvement in stroke patients. Design: Randomized, controlled, parallel, assessor-blinded, three-arm clinical trial. Setting: Southeast University Zhongda Hospital Nanjing, Jiangsu, China. Methods: Seventy patients with hemiplegic stroke were randomly assigned to conventional training (Control, n = 23) or unilateral (URT, n = 23), or bilateral robotic training (BRT, n = 24). The conventional group received routine rehabilitation, 60 min/day, 6 days/week, for 3 weeks. For URT and BRT upper limb robot-assisted rehabilitation training was added. This was 60 min/day, 6 days/week, for 3 weeks. The primary outcome was upper limb motor function assessed with Fugl-Meyer–Upper Extremity Scale (FMA–UE). Secondary outcomes were activities of daily living (ADL) assessed with the Modified Barthel Index (MBI), Motor Evoked Potential (MEP) to assess corticospinal tract connectivity, Root Mean Square (RMS) value, and integrate Electromyography (iEMG) value recorded by surface electromyography to evaluate muscle contraction function. Results: The primary outcome indicator FMA–UE (least square mean (LSMEAN): 31.40, 95% confidence interval (95% CI): 27.74–35.07) and the secondary outcome indicator MBI (LSMEAN: 69.95, 95% CI: 66.69–73.21) were significantly improved in BRT as opposed to control (FMA–UE, LSMEAN: 24.79, 95% CI: 22.23–27.35; MBI, LSMEAN: 62.75, 95% CI: 59.42–66.09); and unilateral (FMA–UE, LSMEAN: 25.97, 95% CI: 23.57–28.36; MBI, LSMEAN: 64.34, 95% CI: 61.01–67.68). BRT also showed greater improvement in the anterior deltoid bundle with regard to muscle contraction function indicated by RMS (LSMEAN: 257.79, 95% CI: 211.45–304.12) and iEMG (LSMEAN: 202.01, 95% CI: 167.09–236.94), as compared to the controls (RMS, LSMEAN: 170.77, 95% CI: 148.97–192.58; iEMG, LSMEAN: 132.09, 95% CI: 114.51–149.68), and URT (RMS, LSMEAN: 179.05, 95% CI: 156.03–202.07; iEMG, LSMEAN: 130.38, 95% CI: 107.50–153.26). There was no statistically significant difference between URT and conventional training for any outcome. There was no significant difference in MEP extraction rate after treatment between groups (p = 0.54 for URT, p = 0.08 for BRT). Conclusions: A 60 min daily training for upper extremities using a three-dimensional end-effector targeting elbow and shoulder adding conventional rehabilitation appears to promote upper limb function and ADL in stroke patients only if delivered bilaterally. URT does not seem to result in better outcomes than conventional rehabilitation. Electrophysiological results suggest that training using a bilateral upper limb robot increases the recruitment of motor neurons rather than improving the conduction function of the corticospinal tract.

Spinal cord injury (SCI) starts with a mechanical and/or bio-chemical insult, followed by a secondary phase, leading progressively to severe collapse of the nerve tissue. Compared to the peripheral nervous system, injured spinal cord is characterized by weak axonal regeneration, which leaves most patients impaired or paralyzed throughout lifetime. Therefore, confining, alleviating, or reducing the expansion of secondary injuries and promoting functional connections between rostral and caudal regions of lesion are the main goals of SCI therapy. Interleukin 10 (IL-10), as a pivotal anti-inflammatory and immunomodulatory cytokine, exerts a wide spectrum of positive effects in the treatment of SCI. The mechanisms underlying therapeutic effects mainly include anti-oxidative stress, limiting excessive inflammation, anti-apoptosis, antinociceptive effects, etc. Furthermore, IL-10 displays synergistic effects when combined with cell transplantation or neurotrophic factor, enhancing treatment outcomes. This review lists pleiotropic mechanisms underlying IL-10-mediated neuroprotection after SCI, which may offer fresh perspectives for clinical translation.

Background: Temporal changes in brain structure and function following rehabilitation, and their relationship with positive recovery in stroke patients experiencing hemiplegia, remain unclear. This study used multimodal magnetic resonance imaging (MRI) to investigate the longitudinal changes in the brains of stroke patients with good outcomes after motor rehabilitation.Methods: Eight subcortical ischemic stroke patients with hemiplegia were enrolled. Multimodal MRI data and clinical assessments were collected in the stable post-acute period and at a 3-month follow-up. Functional connectivity (FC) was calculated for motor-related regions of interest (ROIs) based on functional MRI data. Gray matter volumes (GMVs) and diffusion tensor imaging (DTI) parameters were analyzed to evaluate the temporal changes during recovery.Results: Compared with initial scans, follow-up scans revealed FC changes between several brain regions, e.g., FC increased between the ipsilesional thalamus and the contralesional middle temporal gyrus (MTG). Increased GMV was observed in the contralesional MTG, while GMV decreased in the contralesional cerebellum, correlating with Action Research Arm Test (ARAT) scores at follow-up.Conclusion: The findings suggest that MTG is a key area for neuronal activation and functional reconstruction in stroke patients during motor recovery. These results deepen our understanding of the imaging manifestations of structural and functional neural remodeling during rehabilitation.