Although post-ischemic inflammation induced by the innate immune response is considered an essential step in the progression of cerebral ischemia injury, the role of triggering receptor expressed on myeloid cells 2 (TREM2) in the pathogenesis of ischemic stroke remains to be elucidated. Here, we found that the transcriptional and post-transcriptional levels of TREM2 were increased in cultured primary microglia after oxygen-glucose deprivation and reoxygenation and in the ischemic penumbra of the cerebral cortex after middle cerebral artery occlusion (MCAO) and reperfusion in mice. TREM2 was mainly expressed in microglia, but not in astrocytes, neurons, or oligodendrocytes in mice subjected to MCAO. Manipulating TREM2 expression levels in vitro and in vivo significantly regulated the production of pro-and anti-inflammatory mediators after ischemic stroke. TREM2 overexpression markedly suppressed the inflammatory response and neuronal apoptosis. By contrast, TREM2 gene silencing intensified the inflammatory response, increased neuronal apoptosis and infarct volume, and further exacerbated neurological dysfunction. Our study demonstrated that TREM2 protects against cerebral ischemia/ reperfusion injury through the aspect of post-ischemic inflammatory response and neuronal apoptosis. Pharmacological targeting of TREM2 to suppress the inflammatory response may provide a new approach for developing therapeutic strategies in the treatment of ischemic stroke and other cerebrovascular diseases.

ObjectivesAs a non-invasive therapy, whether transcranial magnetic stimulation (TMS) is effective on migraine. This article was aimed to assess the efficacy of TMS on migraine based on randomized controlled trails (RCTs).MethodsWe searched PubMed, Embase and Cochrane Library electronic databases for published studies which compared TMS group with sham group, conducted a meta-analysis of all RCTs.ResultsFive studies, consisting of 313 migraine patients, were identified. Single-pulse transcranial magnetic stimulation is effective for the acute treatment of migraine with aura after the first attack (p = 0.02). And, the efficacy of TMS on chronic migraine was not significant (OR 2.93; 95% CI 0.71–12.15; p = 0.14).ConclusionsTMS is effective for migraine based on the studies included in the article.

Background and Aims Alcohol use disorders (AUD) are often comorbid with depressive symptoms. Cohort studies on the association between AUD and subsequent depressive symptoms have produced inconsistent results. Moreover, regarding alcohol intake, the risk of developing depressive symptoms might vary with alcohol intake level. We aimed to investigate the association between AUD, alcohol intake and subsequent depressive symptoms. Design and Setting We conducted a systematic search in PubMed, Embase and PsycINFO for cohort studies on the association between AUD or alcohol intake and subsequent depressive symptoms. Participants We included 338 426 participants from 42 studies. Six and four studies analyzed only females and males, respectively. Measurements We combined risk estimates for developing depressive symptoms using a random‐effects model. We divided alcohol intake into abstinence, light (0–84 g/week), moderate (85–168 g/week) and heavy drinking (> 168 g/week or > 48 g/day at least weekly). We conducted a categorical analysis to compare the risk of depressive symptoms between abstinence and different intake categories. Further, we conducted a dose–response analysis to investigate the alcohol–depression association. Findings We analyzed 42 studies (follow‐up time: 1–40 years). AUD was associated with significantly increased risk of subsequent depressive symptoms [relative risk (RR) = 1.57, 95% confidence interval (CI) = 1.41–1.76]. Regarding alcohol intake, heavy drinking had an increased risk of depressive symptoms; however, the association was only significant when controls were limited to non‐heavy drinkers (RR = 1.13, 95% CI = 1.05–1.22). Taking into consideration the possibility of publication bias and confounding factors made the association non‐significant. We observed J‐shaped associations in both categorical and dose–response analyses where light‐moderate drinking had a significantly decreased risk of depression, while heavy drinking did not show a significant association with depressive symptoms compared with non‐drinkers. Conclusion Alcohol use disorders are associated with increased the risk of subsequent depressive symptoms. Heavy drinking does not significantly predict occurrence of depressive symptoms after adjusting for potential confounders.

BackgroundGlioblastoma multiforme (GBM) induces tumor immunosuppression through interacting with tumor-infiltrating microglia or macrophages (TAMs) with an unclear pathogenesis. Enhancer of zeste homolog 2 (EZH2) is abundant in GBM samples and cell lines and is involved in GBM proliferation, cell cycle, and invasion, whereas its association with innate immune response is not yet reported. Herein, the aim of this study was to investigate the role of EZH2 in GBM immune.MethodsCo-culturing models of human/murine GBM cells with PBMC-derived macrophages/primary microglia were employed. EZH2 mRNAs and function were suppressed by siEZH2 and DZNep. Real-time PCR and flow cytometry were used to determine levels of microglia/macrophages markers. The fluorescence-labeled latex beads and flow cytometry were utilized to evaluate phagocytic abilities of microglia. CCK8 assay was performed to assess microglia proliferation.ResultsEZH2 inhibition led to significant reduction of TGFβ1-3 and IL10 and elevation of IL1β and IL6 in human and murine GBM cells. More importantly, EZH2 suppression in GBM cells resulted in significant increase of M1 markers (TNFα and iNOS) and decrease of a pool of M2 markers in murine microglia. The proportion of CD206+ cells was decreased in PBMC-derived macrophages as co-incubated with EZH2-inhibited GBM cells. Functional researches showed that phagocytic capacities of microglia were significantly ameliorated after EZH2 inhibition in co-culturing GBM cells and microglia proliferation was declined after addition of TGFβ2 antibodies to co-incubated GBM cells with EZH2 inhibition. Besides, we found that EZH2 suppression in GBM cells enhanced co-culturing microglia engulfment through activation of iNOS.ConclusionsOur data demonstrates that EZH2 participates in GBM-induced immune deficient and EZH2 suppression in GBM can remodel microglia immune functions, which is beneficial for understanding GBM pathogenesis and suggests potential targets for therapeutic approaches.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-0993-4) contains supplementary material, which is available to authorized users.