Long-term repetitive transcranial direct current stimulation in patients with disorders of consciousness: a preliminary study.

OBJECTIVES: To investigate the effects of long-term repetitive transcranial direct current stimulation on patients with DOC in the subacute phase. METHODS: In a randomized, double-blind, controlled study, 33 patients were randomly assigned to the active or sham group, and 28 patients completed the study. Patients in the active group received anodal stimulation over the DLPFC, while patients in the sham group received placebo stimulation (20 min/day, 5 days/week, for 4 weeks). The level of consciousness among patients was assessed with the Coma Recovery Scale-Revised (CRS-R) at baseline and at the end of every week from the first to the fourth week. RESULTS: The CRS-R scores of both the active and sham groups showed a consistent increasing trend over time; however, the treatment effect of the active group was better than that of the sham group. In addition, there was a statistically significant difference in the total CRS-R score between the two groups at weeks 1, 2, 3 and 4. Moreover, 10 patients (71.4%) in the active group and 3 patients (21.4%) in the sham group were regarded as responders. CONCLUSION: Long-term tDCS could improve the level of consciousness of patients with DOC in the subacute stage.

Rapamycin Alleviates the Symptoms of Multiple Sclerosis in Experimental Autoimmune Encephalomyelitis (EAE) Through Mediating the TAM-TLRs-SOCS Pathway.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Our research aimed to find an immunomodulatory therapy for MS. An experimental autoimmune encephalomyelitis (EAE) mouse model of MS was established induced with the syntheticmyelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). Fifty C57BL/6 mice were randomly divided into the Normal group, EAE group, and Rapamycin group (EAE mice treated with three different doses of rapamycin). Hematoxylin and eosin staining and Weil myelin staining were performed on the brain tissues of mice after 21 days post-immunization. The protein expression of Gas6, Tyro3, Axl, Mer in paraventricular tissues were analyzed by immunohistochemistry. The mRNA and protein expression of Gas6, Tyro3, Axl, Mer, SOCS1, SOCS3, Toll-like receptor (TLR) 3, and TLR4 were detected by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. An enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of the inflammatory factors IFN-γ and IL-17. Rapamycin treatment could ameliorate the behavior impairment in EAE mice induced by MOG35-55. The expression of Gas6, Tyro3, Axl, Mer, SOCS1, and SOCS3 were decreased in EAE mice at 21 days post-immunization, while the expression of Gas6, Tyro3, Axl, and Mer in rapamycin group was higher than that in EAE group. It was accompanied by an increase in anti-inflammatory proteins SOCS1 and SOCS3, a decrease in the inflammatory proteins TLR-3, TLR-4 and in the amount of IFN-γ, and IL-17. Rapamycin injection relieved the nerve function of and the loss of myelin sheath in the EAE mice, mainly through mediating the TAM-TLRs-SOCS signaling pathway to regulate natural immunity.

Mechanism of gut microbiota and Axl/SOCS3 in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS). The present study explored the role of intestinal microbiota in the initiation and propagation of mice induced by experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. 48 C57BL/6 were randomly divided into control group and EAE group. The changes of body weight and the scores of neurological function were recorded. The mRNA expression of the receptor tyrosine kinase subfamily (AXL) was detected by real-time quantitative PCR. The levels of IL-17 and IFN-γ in blood samples were examined by ELISA. The intestinal microbial composition of mice at different time points during the EAE induction was analyzed by 16S rRNA gene-based sequencing. In EAE group, the body weight began to reduce at day 3 and neurological symptoms began to appear at day 7 after EAE induction. The levels of IL-17 and IFN-γ in EAE group reached the peak at day 21 and then decreased gradually. However, the expression of Axl and SOCS3 reached the lowest level at day 21 and then increased gradually. The microbiome analyses revealed that the abundances of Alistipes, Blautia, and Lachnospiraceae_NK4A136_group were significantly changed at day 14, whereas the abundances of Allobaculum, Eubacterium and Helicobacter were significantly changed at day 30 of EAE induction. The prevotellaceae_NK3B31_group may be key bacteria that contribute to the development of MS. Regulation of intestinal microbiota composition can become a new therapeutic target for the treatment of MS.

[Effect of Acupuncture on Expression of Receptor Tyrosine Kinase c-kit in Interstitial Cells of Cajal, Carbon Monoxide and Heme Oxygenase in Colon Tissue After Colonic Anastomosis in Rats].

OBJECTIVE: To observe the effect of acupuncture on expression of receptor tyrosine kinase (RTK) c-kit in interstitial cells of Cajal (ICCs), carbon monoxide (CO) and heme oxygenase (HO) in colon tissue after colonic anastomosis, so as to explore the mechanism of acupuncture in improving gastrointestinal motility. METHODS: SD rats were randomly devided into control group, model group and acupuncture group. The model was established using colonic anastomosis. Each group was further devided into 3, 5, and 10 d (time-point) subgroups (n=10 in each). Acupuncture was applied to acupuncture group at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Taichong" (LR 3) for 15 min, once daily after modeling. The first defecation time was recorded, and the intestinal propulsive rate was measured. The expression of c-kit in colon tissue was detected by immunohistochemistry. The content of CO, the activities of HO-1 and HO-2 in colon tissue were detected by biochemical method and ELISA, respectively. RESULTS: Compared to the control group, the intestinal propulsive rate and the expression level of c-kit in ICCs were decreased in the model group(P<0.05), the content of CO and the activity of HO-1 were increased in model 3 d and 5 d subgroups(P<0.05), the activity of HO-2 was increased in model 3 d subgroup(P<0.05), while the opposite results appeared in model 5 d and 10 d subgroups(P<0.05). Compared to the model group, the first defecation time was shortened (P<0.05), the intestinal propulsive rate and the expression level of c-kit in ICCs were increased in the acupuncture group (P<0.05), the content of CO and the activity of HO-1 were decreased in acupuncture 3 d and 5 d subgroups(P<0.05), the activity of HO-2 was decreased in acupuncture 3 d subgroup(P<0.05), while the opposite result appeared in acupuncture 10 d subgroup(P<0.05). Compared to the 3 d subgroup, the intestinal propulsive rate and the expression level of c-kit in ICCs were increased, the content of CO, the activities of HO-1 and HO-2 were decreased in both model and acupuncture 5 d subgroups (P<0.05). In model 10 d subgroup, the intestinal propulsive rate and the expression level of c-kit in ICCs were increased, the content of CO and the activity of HO-1 were decreased in comparison with the model 5 d subgroup(P<0.05). CONCLUSIONS: Acupuncture can improve postoperative gastrointestinal motility by declining CO content and HO-1 and HO-2 activity in colon tissue, and promoting ICCs restoration.

Atorvastatin calcium in combination with methylprednisolone for the treatment of multiple sclerosis relapse.

This study aimed to investigate the efficacy of combined atorvastatin calcium and methylprednisolone for the treatment of multiple sclerosis relapse. Patients with multiple sclerosis (MS) at the relapse phase were randomized to receive either combined treatment of atorvastatin calcium and methylprednisolone (n = 19) or methylprednisolone alone (n = 19). Expanded Disability Status Scale (EDSS) was administered at baseline, 1 week, 2 weeks, 4 weeks, 3 months, and 6 months after treatment initiation. The number and volume of brain lesions were evaluated using magnetic resonance imaging at baseline and 6 months. The levels of IL-13, IL-35, IFN-γ, and IL-10 in the cerebrospinal fluid were examined using the enzyme-linked immunosorbent assay method. There was no significant difference in EDSS scores at 1, 2, and 4 weeks. At 3 and 6 months, the combined treatment group showed significantly lower EDSS scores than the monotherapy group (P < 0.05). The number and volume of brain lesions in the combined treatment group were significantly lower than the monotherapy group at 6 months (P < 0.001). The mean time to relapse was significantly extended in the combined treatment group than the monotherapy group (P < 0.001). At 2 and 4 weeks, the combined treatment group had significantly higher levels of IL-13, IL-35, and IL-10 in the cerebrospinal fluid than the monotherapy group (P < 0.05), but significantly lower level of IFN-γ (P < 0.001). The levels of IL-13 and IL-10 in the combined treatment group were positively correlated with EDSS scores (r = 0.632, P = 0.001; r = 0.731, P = 0.002). Combined treatment with atorvastatin calcium and methylprednisolone can improve the outcomes of MS relapse compared with glucocorticosteroid alone.