Increasing toll-like receptor 2 on astrocytes induced by Schwann cell-derived exosomes promotes recovery by inhibiting CSPGs deposition after spinal cord injury.

BACKGROUND: Traumatic spinal cord injury (SCI) is a severely disabling disease that leads to loss of sensation, motor, and autonomic function. As exosomes have great potential in diagnosis, prognosis, and treatment of SCI because of their ability to easily cross the blood-brain barrier, the function of Schwann cell-derived exosomes (SCDEs) is still largely unknown. METHODS: A T10 spinal cord contusion was established in adult female mice. SCDEs were injected into the tail veins of mice three times a week for 4 weeks after the induction of SCI, and the control group was injected with PBS. High-resolution transmission electron microscope and western blot were used to characterize the SCDEs. Toll-like receptor 2 (TLR2) expression on astrocytes, chondroitin sulfate proteoglycans (CSPGs) deposition and neurological function recovery were measured in the spinal cord tissues of each group by immunofluorescence staining of TLR2, GFAP, CS56, 5-HT, and ß-III-tublin, respectively. TLR2f/f mice were crossed to the GFAP-Cre strain to generate astrocyte specific TLR2 knockout mice (TLR2-/-). Finally, western blot analysis was used to determine the expression of signaling proteins and IKKß inhibitor SC-514 was used to validate the involved signaling pathway. RESULTS: Here, we found that TLR2 increased significantly on astrocytes post-SCI. SCDEs treatment can promote functional recovery and induce the expression of TLR2 on astrocytes accompanied with decreased CSPGs deposition. The specific knockout of TLR2 on astrocytes abolished the decreasing CSPGs deposition and neurological functional recovery post-SCI. In addition, the signaling pathway of NF-κB/PI3K involved in the TLR2 activation was validated by western blot. Furthermore, IKKß inhibitor SC-514 was also used to validate this signaling pathway. CONCLUSION: Thus, our results uncovered that SCDEs can promote functional recovery of mice post-SCI by decreasing the CSPGs deposition via increasing the TLR2 expression on astrocytes through NF-κB/PI3K signaling pathway.

Effects of therapeutic ultrasound for knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness and safety of therapeutic ultrasound with sham ultrasound on pain relief and functional improvement in knee osteoarthritis patients. As phonophoresis is a unique therapeutic ultrasound, we also compared the effects of phonophoresis with conventional non-drug ultrasound. DATA SOURCES: PubMed, EMBASE, and the Cochrane Library were systematically searched for randomized controlled trials from inception up to June 2019. REVIEW METHODS: Randomized controlled trials comparing therapeutic ultrasound with sham ultrasound in knee osteoarthritis patients were included. Phonophoresis in the experimental and control groups were compared through conventional ultrasound, and corresponding trials were also included. Two reviewers independently identified eligible studies and extracted data. Risk of bias assessments and therapeutic ultrasound safety assessments were also performed. RESULTS: Fifteen studies including three phonophoresis-related studies with 1074 patients were included. Meta-analyses demonstrated that therapeutic ultrasound significantly relieved pain (P < 0.00001) and reduced the Western Ontario and McMaster Universities (WOMAC) physical function score (P = 0.03). In addition, therapeutic ultrasound increased the active range of motion (P < 0.00001) and reduced the Lequesne index (P < 0.00001). Subgroup analysis of phonophoresis ultrasound illustrated significant differences on the visual analogue scale (P = 0.009), but no significant differences on WOMAC pain subscales (P = 0.10), and total WOMAC scores were observed (P = 0.30). There was no evidence to suggest that ultrasound was unsafe treatment. CONCLUSIONS: Therapeutic ultrasound is a safe treatment to relieve pain and improve physical function in patients with knee osteoarthritis. However, phonophoresis does not produce additional benefits to functional improvement, but may relieve pain compared to conventional non-drug ultrasound.

Meta-analysis of heparin therapy for preventing venous thromboembolism in acute spinal cord injury.

OBJECTIVE: Venous thromboembolism (VTE) is a frequent complication in patients with acute spinal cord injury (SCI) and may have serious consequences. This study aimed to assess the efficacy and safety of heparin and low-molecular-weight heparin (LMWH) venous thromboprophylaxis in patients with acute SCI. METHODS: PubMed, Web of Science, EMBASE and the Cochrane library were searched from January 1980 to August 2016. The primary outcome was the incidence of VTE. Secondary outcomes included the incidences of Deep-vein thrombosis (DVT), pulmonary embolism (PE) and major bleeding. RESULTS: A total of 11 studies including 1605 patients qualified for inclusion. Four studies evaluated the efficacy of heparin treatment compared with placebo or no treatment. There were significant differences between the two treatments, and the summary RR was 0.35 (95% confidence interval (CI) 0.15-0.87; P = 0.02). Seven studies compared low dose unfractionated heparin (LDUH) with LMWH. The incidence of VTE was not significantly different between the two treatments (RR 1.09, 95% CI 0.63-1.89; P = 0.76). There were no differences in the incidence of major bleeding with unfractionated heparin versus LMWH (summary RR 1.32, 95% CI 0.62-2.84; P = 0.47). CONCLUSIONS: In this meta-analysis, heparin exhibited protective effects compared with placebo or no treatment with respect to the occurrence of VTE; there were no differences between LMWH and unfractionated heparin with ret to thromboembolism prophylaxis efficacy. LMWH did not reduce the risk of bleeding compared with LDUH.