Stroke poses a serious threat to human health and burdens both society and the healthcare system. Standard rehabilitative therapies may not be effective in improving functions after stroke, so alternative strategies are needed. The FDA has approved vagus nerve stimulation (VNS) for the treatment of epilepsy, migraines, and depression. Recent studies have demonstrated that VNS can facilitate the benefits of rehabilitation interventions. VNS coupled with upper limb rehabilitation enhances the recovery of upper limb function in patients with chronic stroke. However, its invasive nature limits its clinical application. Researchers have developed a non-invasive method to stimulate the vagus nerve (non-invasive vagus nerve stimulation, nVNS). It has been suggested that nVNS coupled with rehabilitation could be a promising alternative for improving muscle function in chronic stroke patients. In this article, we review the current researches in preclinical and clinical studies as well as the potential applications of nVNS in stroke. We summarize the parameters, advantages, potential mechanisms, and adverse effects of current nVNS applications, as well as the future challenges and directions for nVNS in cerebral stroke treatment. These studies indicate that nVNS has promising efficacy in reducing stroke volume and attenuating neurological deficits in ischemic stroke models. While more basic and clinical research is required to fully understand its mechanisms of efficacy, especially Phase III trials with a large number of patients, these data suggest that nVNS can be applied easily not only as a possible secondary prophylactic treatment in chronic cerebral stroke, but also as a promising adjunctive treatment in acute cerebral stroke in the near future.

Objective To determine the effects of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for people with incomplete spinal cord injury. Methods PubMed, Embase, Web of Science, PEDro, CENTRAL and CINAHL were searched from inception until September 4, 2022. Randomized controlled trials that evaluated the effects of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for individuals with incomplete spinal cord injury were selected. Mean differences (MD) with 95% confidence interval (CI) were calculated. The methodological quality was evaluated by the Cochrane Risk of Bias 2.0 tool. Subgroup analyses were conducted according to the time since injury. Results In total 19 studies involving 770 patients were eligible for analysis. Individuals with acute incomplete spinal cord injury in robotic-assisted gait training groups showed significantly greater improvements in 6-minute walking test (MD 53.32; 95% CI 33.49 to 73.15; P < 0.001), lower extremity motor scale (MD 5.22; 95% CI 3.63 to 6.80; P < 0.001) and walking index for spinal cord injury II (MD 3.18; 95% CI 1.34 to 5.02; P < 0.001). Robotic-assisted gait training improved peak oxygen consumption to a greater degree for chronic incomplete spinal cord injury patients (MD 4.90; 95% CI 0.96 to 8.84; P = 0.01). Conclusion Robot-assisted gait training may be a feasible and effective intervention in terms of cardiopulmonary fitness and exercise capacity for individuals with incomplete spinal cord injury.

Objective Low-frequency vibration accelerates cartilage degeneration in knee osteoarthritis (KOA) rat model. In this article, we investigated whether whole-body vibration (WBV) increases cartilage degeneration by regulating tumor necrosis factor-α (TNF-α) in KOA. Design Proteomics analysis was used to filter candidate protein from synovial fluid (SF) in KOA people after WBV. Enzyme-linked immunosorbent assay (ELISA) was used to estimate changes in TNF-α levels in SF. The C57 mice and TNF-α knock-out mice were sacrificed for the KOA model and WBV intervention. The cartilage was tested by ELISA, histology, terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL), immunohistochemistry, and reverse transcriptase polymerase chain reaction. Luciferase activity test in vitro study was conducted to confirm the relationship between TNF-α and the candidate protein. Results Differentially expressed proteins were enriched in the glycolytic process, glucose catabolic, and regulation of interleukin-8 (IL-8) secretion processes. Phosphoglycerate kinase, triosephosphate isomerase 1, T cell immunoglobulin- and mucin-domain-containing molecules 2, fumarylacetoacetate hydrolase (FAH), and TNF were the hub node. TNF-α expression increased in SF after WBV ( P < 0.05). The cartilage was more degenerated in the TNF-α−/− mice group compared to controls. A significant change was observed in collagen II and FAH ( P < 0.05). TNF-α expression improved in C57 mice ( P < 0.05). Apoptosis of chondrocytes was inhibited in TNF-α−/− mice by the TUNEL test. Luciferase activity significantly increased in TNF-α + FAH-Luc cells ( P < 0.05). Conclusion A novel mechanism underlying WBV-triggered cartilage degeneration was found in KOA that demonstrated the critical regulatory function of TNF-α and FAH during WBV.

Acupuncture therapies were used to treat spinal cord injury (SCI) and its complications. To assess the effect of a specific acupuncture therapy combined with rehabilitation training for inpatients with incomplete SCI, we conducted an assessor-blinded, randomized controlled clinical trial in the Department of Rehabilitation Medicine Center in West China Hospital, Sichuan University. Seventy-two participants diagnosed with incomplete SCI were randomly assigned into 3 groups of 24 patients each, with data collection completed in December, 2019. Participants were randomly assigned (1 : 1 : 1) to 3 groups to receive treatment for 4 weeks, 5 times/week of acupuncture for Continuous Acupuncture Treatment (CAT) group, 3 times/week for Intermittent Acupuncture Treatment (IAT) group, and no acupuncture for Control group; all 3 groups received routine rehabilitation training. The primary outcome was the change of American Spinal Injury Association (ASIA) motor score from baseline to week 4. Secondary outcomes included sensory score, Modified Barthel Index (MBI). At week 4, CAT group had a higher motor score and MBI score increase than the control group (mean difference 10.52, 17.36; p  < 0.001, p  < 0.01, respectively). CAT group had more increase in motor score and MBI than IAT group (mean difference 5.55, 14.77; p  < 0.05, p  < 0.05, respectively). But the difference among groups in the increase of sensory score was not statistically significant. Acupuncture resulted in a higher motor score and MBI after 4 weeks. And the dosage of 5/week led to more improvement in motor score and MBI than that of 3/week. The results suggested that a dosage of 5/week of acupuncture is safe and more effective for SCI than 3/week. But further research is needed to determine the best intervention dosage, long-term efficacy, and underlying mechanism. This trial is registered with ChiCTR1900021530.

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Spinal cord injury (SCI) is a devastating condition with complex pathological mechanisms that lead to sensory, motor, and autonomic dysfunction below the site of injury. To date, no effective therapy is available for the treatment of SCI. Recently, bone marrow-derived mesenchymal stem cells (BMMSCs) have been considered to be the most promising source for cellular therapies following SCI. The objective of the present review is to summarize the most recent insights into the cellular and molecular mechanism using BMMSC therapy to treat SCI. In this work, we review the specific mechanism of BMMSCs in SCI repair mainly from the following aspects: Neuroprotection, axon sprouting and/or regeneration, myelin regeneration, inhibitory microenvironments, glial scar formation, immunomodulation, and angiogenesis. Additionally, we summarize the latest evidence on the application of BMMSCs in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models.