Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway.

PURPOSE: Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation. METHODS: C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. RESULTS: Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol. CONCLUSIONS: Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Inflammation and comorbidities of chronic obstructive pulmonary disease: The cytokines put on a mask!

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a well-known complex multicomponent disease characterized by systemic inflammation that frequently coexists with other conditions. We investigated the relationship between some inflammatory markers and complications in COPD patients to explore the possible roles of inflammation in these comorbidities. METHODS: This study used cross-sectional and case-control methods. We included 336 hospitalized COPD patients, 64 healthy controls, and 42 major depression patients and evaluated all participants using the Hamilton Rating Scale. C-reactive protein (CRP), red blood cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were collected and measured in the study population. Statistical methods were used to analyze the association of inflammatory markers with COPD comorbidities. RESULTS: Cor pulmonale and psychological comorbidities (depression and anxiety) were more common in this study on COPD patients. We found that MLR (OR = 2.054, 95 % CI 1.129-3.735, p = 0.018) and RDW (OR = 1.367, 95 % CI 1.178-1.586, p = 0.000) were related to COPD patients complicated with cor pulmonale, while IL-6 (OR = 1.026, 95 % CI 1.001-1.053, p = 0.045) and RDW (OR = 1.280, 95 % CI 1.055-1.552, p = 0.012) were related to depression symptoms. CONCLUSION: MLR, RDW and IL-6 were closely related to cor pulmonale and depression in COPD patients. IL-1 ß and IL-6 are closely related to depression in humans.

Development of a Resocialization Scale for Chinese Older Adult Migrants.

With a rapidly aging population in China, resocialization is a concern amidst an increasing influx of older adult migrants. The aim of the current study was to develop a resocialization assessment scale for older migrants within the Chinese context. The study was conducted in two phases. A literature review and qualitative interview were performed to generate a draft scale that was further examined through Delphi expert consultation. Participants comprised 509 older migrants selected for a questionnaire survey. Analysis identified 62 items across four factors: interpersonal relationships, behavioral patterns, cultural integration, and social roles. Reliability and validity of the resulting assessment scale were verified. The scale can be used to evaluate the degree of resocialization exhibited by older migrants in Chinese communities. [Research in Gerontological Nursing, 15(5), 245-253.].

[Research progress on the molecular regulatory mechanism of exosome biogenesis].

Exosomes are small vesicles with a diameter of about 40-160 nm actively secreted by cells. They participate in a variety of pathophysiological processes and are closely related to the occurrence and development of diseases. As a newly carrier of intercellular communication and circulating biomarkers of disease diagnosis and prognosis, exosomes have attracted great attention for their potential clinical applications. However, many aspects such as exosome biogenesis, targeted transport, and mechanism of action are still unclear. This paper focuses on the exosome biogenesis, summarizes the exosome biogenesis pathways, and describes relevant molecular modulation mechanisms of importance. And this review provides a theoretical basis for disease treatment based on regulating exosome production.

Aconitine induces brain tissue damage by increasing the permeability of the cerebral blood-brain barrier and over-activating endoplasmic reticulum stress.

OBJECTIVE: This study aimed to explore the neurotoxicity of aconitine and its underlying mechanism. METHODS: The rats were administered with the aconitine solution intragastrically at different dosages (0.5 mg/kg, 1.5 mg/kg, and 2.5 mg/kg). Evans blue (EB) extravasation and evaluation of tight junction protein expression were performed to determine the permeability of the blood-brain barrier. Cellular damage, apoptosis, and levels of endoplasmic reticulum (ER) stress markers were determined using H&E staining, Tunnel assay, and western blotting. The effects of aconitine on cell viability, apoptosis, and activation of the ER stress signaling in PC12 cells were assessed in vitro using the MTT assay, flow cytometry, western blot, and immunofluorescence analysis. RESULTS: Aconitine was observed to significantly increase the murine blood-brain barrier penetrability in a dose-dependent manner. The in vivo experimental results revealed that aconitine could stimulate the pathway for endoplasmic reticulum stress. The increase in the endoplasmic reticulum stress in the brain tissue promoted apoptosis, leading to brain damage. Moreover, PC12 cell proliferation was inhibited upon treatment with aconitine in a dose-dependent manner. In addition, cell apoptosis was increased upon treatment with aconitine also in a dose-dependent manner. These findings indicated that aconitine caused damage to PC12 cells via endoplasmic reticulum stress. CONCLUSION: Aconitine induces brain tissue damage by increasing the penetrability of the blood-brain barrier in the cerebral region and over-activating the endoplasmic reticulum stress.

Diagnostic Value of Aortic Dissection Risk Score, Coagulation Function, and Laboratory Indexes in Acute Aortic Dissection.

Objective: This study was aimed at studying the diagnostic value of aortic dissection (AD) risk score, coagulation function, and laboratory indicators in acute aortic dissection (AAD). Methods: In this retrospective study, 57 patients with AAD and 57 with an acute coronary syndrome (ACS). During the same period, 50 healthy subjects were selected as the control group admitted to our institution which were assessed for eligibility and recruited. They were assigned to an AD group (AAD patients) and an ACS group (ACS patients). The AD risk scores, coagulation function indexes, and laboratory indexes of the two groups were compared. With digital subtraction angiography- (DSA-) based diagnosis result as the gold standard, the receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of various indexes for AD, and the sensitivity, specificity, and optimal diagnostic value (Youden index) of the diagnostic indexes were calculated. Additionally, the overall blood clot formation strength (MA), clotting factor function (R), platelet function (MAp), and functional fibrinogen (MAf) levels were evaluated. Results: AAD risk, AD screening, early diagnosis of AAD, fibrinogen degradation products (FDP), fibrinogen (Fib), prothrombin time (PT), activated partial thromboplastin time (APTT), tenascin C (TN-C), D-dimer (D-D), and N-terminal B-type natriuretic peptide precursor (NT-proBNP) in the three groups were statistically different (P < 0.05). Further pairwise comparisons showed that the AD patients got higher scores of AAD risk, AD screening, and early diagnosis of AAD versus ACS patients (P < 0.05). AD was associated with lower levels of fibrinogen degradation products (FDP) and fibrinogen (Fib), shorter prothrombin time (PT), and activated partial thromboplastin time (APTT) versus ACS (P < 0.05). AD also resulted in higher levels of tenascin C (TN-C), D-dimer (D-D), and N-terminal B-type natriuretic peptide precursor (NT-proBNP) versus ACS (P < 0.05). The three risk scores, various laboratory indicators, and various coagulation function indicators were of high diagnostic values for the diagnosis of AAD (AUC > 0.9, P < 0.05). The sensitivity of the AD screening scale and TN-C expression level to the diagnosis of AAD was up to 100%, and the specificity of TN-C expression level was up to 98.25%. The influencing factors of AAD included Fib, FDP, PT, APTT, D-D, TN-C, and NT-proBNP. MA, MAf, and MAp displayed the same trend and reached the lowest point at T2. R was the opposite and reached the highest point at T2. At T4, a higher Map and a lower MAf were found than before surgery, and R and MA returned to preoperative levels. The positive detection rate of ACS by CT scan was positively correlated with the degree of stenosis (r = 0.814, P < 0.05). Conclusion: AD screening scale, TN-C, and FDP are of the highest diagnostic value in the risk score of AD, laboratory indicators, and coagulation function. It has implications for the diagnosis of ADD.

Gray-White Matter Ratio at the Level of the Basal Ganglia as a Predictor of Neurologic Outcomes in Cardiac Arrest Survivors: A Literature Review.

Loss of gray-white matter discrimination is the primary early imaging finding within of cranial computed tomography in cardiac arrest survivors, and this has been also regarded as a novel predictor for evaluating neurologic outcome. As displayed clearly on computed tomography and based on sensitivity to hypoxia, the gray-white matter ratio at basal ganglia (GWR-BG) region was frequently detected to assess the neurologic outcome by several studies. The specificity of GWR-BG is 72.4 to 100%, while the sensitivity is significantly different. Herein we review the mechanisms mediating cerebral edema following cardiac arrest, demonstrate the determination procedures with respect to GWR-BG, summarize the related researches regarding GWR-BG in predicting neurologic outcomes within cardiac arrest survivors, and discuss factors associated with predicting the accuracy of this methodology. Finally, we describe the effective measurements to increase the sensitivity of GWR-BG in predicting neurologic outcome.

Actin Alpha 2 Downregulation Inhibits Neural Stem Cell Proliferation and Differentiation into Neurons through Canonical Wnt/ß-Catenin Signaling Pathway.

Our previous study has shown that actin alpha 2 (ACTA2) is expressed in NSC and ACTA2 downregulation inhibits NSC migration by increasing RhoA expression and decreasing the expression of Rac1 to curb actin filament polymerization. Given that proliferation and differentiation are the two main characteristics of NSC, the role of ACTA2 downregulation in the proliferation and differentiation of NSC remains elusive. Here, the results demonstrated that ACTA2 downregulation using ACTA2 siRNA held the potential of inhibiting NSC proliferation using cell counting kit-8 (CCK8) and immunostaining. Then, our data illustrated that ACTA2 downregulation attenuated NSC differentiation into neurons, while directing NSC into astrocytes and oligodendrocytes using immunostaining and immunoblotting. Thereafter, the results revealed that the canonical Wnt/ß-catenin pathway was involved in the effect of ACTA2 downregulation on the proliferation and differentiation of NSC through upregulating p-ß-catenin and decreasing ß-catenin due to inactivating GSK-3ß, while this effect could be partially abolished with administration of CHIR99012, a GSK-3 inhibitor. Collectively, these results indicate that ACTA2 downregulation inhibits NSC proliferation and differentiation into neurons through inactivation of the canonical Wnt/ß-catenin pathway. The aim of the present study is to elucidate the role of ACTA2 in proliferation and differentiation of NSC and to provide an intervention target for promoting NSC proliferation and properly directing NSC differentiation.

Multiple miscarriages in a female patient with two-chambered heart and situs inversus totalis: A case report.

BACKGROUND: Single atrium with single ventricle, or a two-chambered heart, is an extremely rare congenital malformation. Few cases with two-chambered heart surviving to adulthood have been reported. CASE SUMMARY: We reported an adult female patient with a two-chambered heart and situs inversus totalis accompanied by multiple pregnancies and abortions. Magnetic resonance imaging detected a two-chambered heart. B-ultrasound-guided uterine aspiration was performed to absorb 8 g and 10 g of organized villus and decidual tissues, respectively, with a small amount of bleeding. Postoperatively, cyanosis and fatigue-induced shortness of breath were gradually relieved. The patient has currently outlived all similar cases reported so far. CONCLUSION: Hemodynamic changes in pregnant women with two-chambered heart impaired cardiac function, responsible for hypoperfusion and miscarriage.

Multiple Factor Analysis of Depression and/or Anxiety in Patients with Acute Exacerbation Chronic Obstructive Pulmonary Disease.

Objective: To reveal the risk factors, the symptom distribution characteristics, the clinical values of white blood cell counts (WBC counts), red blood cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) combined with depression and/or anxiety. Methods: The study included prospective cross-sectional and case-control studies, and was executed in the Affiliated Hospital of Zunyi Medical University, Guizhou, China. Previously diagnosed chronic obstructive pulmonary disease (COPD) patients who admitted to the hospital with AECOPD, patients with depression and/or anxiety, and healthy people were enrolled in the study. The Hamilton Rating Scales were used to assess all subjects, and the complete blood counts (CBC) were collected. Baseline data and clinical measurement data [spirometry, arterial blood gas analysis, and COPD evaluation test (the CAT scale)] from patients with AECOPD were collected. Results: Of the 307 patients with AECOPD included, 63.5% (N=195) had depressive and/or anxiety symptoms, and 36.5% (N=112) had no symptoms. Sex, respiratory failure, number of comorbidities, number of acute exacerbations in the previous year and the CAT score were closely related to AECOPD combined with depression and/or anxiety (p<0.05). The CAT scale score were the independent risk factor (OR=6.576, 95% CI 3.812-11.342) and significant predictor of AECOPD with depression and/or anxiety (AUC=0.790,95% CI 0.740-0.834); the patients with depression and/or anxiety were more severe and characteristic than the patients with AECOPD combined with depression and/or anxiety; RDW was associated with AECOPD with depression and/or anxiety (p=0.020, OR1.212,95% CI1.03-1.426), and had certain clinical diagnostic value (AUC=0.570,95% CI 0.531-0.626). Conclusion: Depression and anxiety should not be ignored in patients with AECOPD. The severity and quality of life of COPD were closely related to the occurrence of depression and/or anxiety symptoms. In most cases, perhaps depression and anxiety in AECOPD are only symptoms and not to the extents of the diseases. RDW had clinical diagnostic value in AECOPD combined with depression and/or anxiety. NLR, PLR, MLR, and RDW may become the novel indicators for evaluating the degree of inflammation of AECOPD and deserve further research.

Upregulation of miR-133a by adiponectin inhibits pyroptosis pathway and rescues acute aortic dissection.

Acute aortic dissection (AAD) is a cardiovascular emergency caused by the formation of hematoma in the middle layer of the aortic wall. Adiponectin (APN) is an adipose tissue-specific protein that has anti-inflammation and anti-atherosclerosis functions. Pyroptosis, as an inflammatory cell death, depends on the activation of caspase1, while nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) is a typical representative of the pyroptosis pathway. In this study, we aimed to find whether APN affects the AAD process. The results showed that APN overexpression (OE) inhibited the AAD development and the levels of glucose, triglyceride, and total cholesterol in mice model. In addition, APN OE inhibited the productions of gasdermin D (GSDMD), NLRP3, caspase1, interleukin-1ß (IL-1ß), IL-18, and osteopontin (OPN), as well as α-smooth muscle actin (α-SMA) downregulation in vitro and in vivo. In addition, NLRP3 was found to be a target gene of miR-133a and miR-133a OE showed similar effects to APN OE in attenuating the LPS-induced productions of GSDMD, NLRP3, caspase1, IL-1ß, IL-18, and OPN, as well as α-SMA downregulation in vascular smooth muscle cells (vSMCs). Moreover, the beneficial effects of APN OE were abolished by miR-133a knockdown in vSMCs. In conclusion, our present results indicated that the upregulation of miR-133a by APN inhibits pyroptosis pathway, which potentially rescues AAD.

[Diffusion tensor imaging and resting-state functional magnetic resonance imaging in patients with delirium in intensive care unit].

OBJECTIVE: To analyze the brain function of patients with delirium in intensive care unit (ICU) using resting-state functional magnetic resonance imaging (fMRI), further analyze the structural changes in the brain using diffusion tensor imaging (DTI), and explore the correlations of brain function with structural changes in patients with delirium in ICU from a new perspective of functional imaging, provide visual evidence for the diagnosis of delirium. METHODS: Patients with delirium admitted to ICU of the Affiliated Hospital of Zunyi Medical University from January 1st to December 31st in 2017 were enrolled as subjects. During the same period, the healthy volunteers who matched the gender, age and education level of the patients with delirium were enrolled as control group. The intensive care delirium screening checklist (ICDSC) scores within 24 hours after ICU admission were recorded. All the subjects were scanned by fMRI and DTI. The abnormal changes in resting-state brain function of the patients with delirium were evaluated by cerebral regional homogeneity (ReHo) data analysis. The DTI data were processed by the FSL software, and the fractional anisotropy (FA) and mean diffusivity (MD) of the brain were extracted, respectively, to evaluate the damage to brain structure. The values of ReHo, FA and MD were compared between the two groups. The ReHo value of brain region with reduced ReHo value of patients with delirium as compared with the healthy volunteers was extracted for Pearson correlation analysis with ICDSC scores. RESULTS: A total of 22 patients with delirium were included. Seven patients who did not cooperate in the examination, used sedatives or had false images in scanning, were excluded. Finally, 15 patients were enrolled in the delirium group, and 15 healthy volunteers in the healthy control group. (1) No statistically significant difference was found in gender, age or education time between the two groups. ICDSC score of the delirium group was significantly higher than that of the healthy control group (6.07±1.28 vs. 1.07±0.88, P < 0.01). (2) fMRI scanning and analysis results: compared with the healthy control group, the ReHo values of the cerebellum, right hippocampus, striatum, midbrain and pons in the delirium group were significantly increased (all P < 0.05, AlphaSim correction), while the ReHo values of bilateral superior frontal gyrus, bilateral median frontal gyrus, left inferior frontal gyrus, temporal lobe and parietal lobe were significantly lowered (all P < 0.05, AlphaSim correction). Correlation analysis showed that the ReHo value of the left superior frontal gyrus was negatively correlated with ICDSC score in the patients with delirium (r = -0.794, P < 0.05), indicating that the changes in the functional area of the medial frontal gyrus was most closely related to delirium. (3) DTI scanning and analysis results: compared with the healthy control group, the FA values of the left cerebellum, bilateral frontal lobes, left temporal lobe, corpus callosum and left hippocampus in the delirium group were decreased significantly (all P < 0.05, AlphaSim correction), while the MD values of the medial frontal gyrus, right superior temporal gyrus, anterior cingulate gyrus, bilateral insular lobes and left caudate nucleus were enhanced significantly (all P < 0.05, AlphaSim correction), suggesting that the structural and functional damage was found in multiple brain regions in patients with delirium. CONCLUSIONS: Multiple brain regions of patients with delirium present abnormal resting-state brain function. The abnormal resting-state brain function of the left superior frontal gyrus is closely related to the occurrence of delirium. Structural damage is found in multiple brain regions of patients with delirium. The structural changes in the frontal lobe, temporal lobe, corpus callosum, hippocampus and cerebellum and their abnormal functions can be used as preliminary imaging indexes for the diagnosis of delirium.

Statin use and risk of tuberculosis: a systemic review of observational studies.

OBJECTIVES: Statin intake may be linked with a lower risk of several infectious diseases, including tuberculosis, which is an important cause of mortality worldwide. The aim of this study was to investigate the definite impacts of statins on the risk of tuberculosis (TB) in diabetic patients and in the general population. METHODS: Four databases were thoroughly searched from inception up to July 2019. Articles in any language were included if they assessed and clarified statin intake, presented the risk of TB in diabetes mellitus (DM) patients or the general population, and reported odds ratios (ORs), relative risks (RRs), or hazard ratios (HRs) or contained data for relevant calculation. RRs with 95% confidence intervals (CIs) were pooled using random-effects models regardless of heterogeneity quantified by Cochran's Q and I2 statistics. RESULTS: Six articles reporting observational studies involving 2 073 968 patients were included. Four reported cohort studies, one a nested case-control study, and one was an abstract. Statin use significantly reduced the risk of TB in DM patients by 22% (pooled RR 0.78, 95% CI 0.63-0.95), with severe heterogeneity (I2 = 76.1%). Statin intake also significantly decreased the risk of TB in the general population by 40% (pooled RR 0.60, 95% CI 0.50-0.71), with severe heterogeneity (I2 = 57.7%). CONCLUSIONS: Statin use is related to a considerably lower risk of TB in both DM patients and the general population. However, these conclusions should be interpreted with caution given the possible remaining confounding, and call for large-size and multicenter randomized controlled studies in the future.

Tim-3 enhances brain inflammation by promoting M1 macrophage polarization following intracerebral hemorrhage in mice.

Macrophage polarization contributes to brain inflammation following spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) has been identified to induce macrophage mediated inflammation following ICH. However, the regulation of Tim-3 on macrophage polarization following ICH has not been fully studied. In current experiment, we explored Tim-3 expression, macrophage polarization, brain water content and neurological function in WT and Tim-3-/- ICH mice. In addition, downstream transcriptional factor TRIF and IRF3 were also analyzed. We found that ICH promoted Tim-3 expression and M1 polarization in the perihematomal region of WT mice, leading to increased brain water content and neurological impairment. However, deletion of Tim-3 expression attenuated M1 polarization, decreased rain water content and improved neurological function of ICH mice. Furthermore, Tim-3 signal promoted transcriptional factors TRIF and IRF3 levels, regulating macrophage polarization. The data suggested that Tim-3 played a crucial role in the macrophage polarization and brain inflammation following ICH, and might represent a promising way in ICH therapy.

miRNA-144 induces microglial autophagy and inflammation following intracerebral hemorrhage.

Autophagic activation mediated inflammation contributes to brain injury of intracerebral hemorrhage (ICH). MiRNAs play a key role in inflammation, which negatively and posttranscriptionally regulate gene expression and function. Modulating the mTOR signal, a central regulator of autophagy, could be of great significance for ICH. However, the specific of miRNA is unknown. In the current study, we detected the miRNA-144 expression, autophagic activity and inflammation of microglia in ICH. We also knocked down endogenous miRNA-144 to regulate autophagy and inflammation in ICH. In addition, we assessed the neurological damge in ICH mice. We found that ICH promoted miRNA-144 expression but downregulated mTOR expression. In addition, upregulation of mTOR attenuated microglial autophagy and inflammation in ICH. Furthermore, downregulation of miRNA-144 also inhibited inflammation, brain edema and improved neurological functions in ICH mice. Taken together, our findings suggested that miRNA-144 was a crucial regulator of autophagy via regulation of mTOR, and represented a promising therapeutical strategy for ICH.

MiR-124 contributes to M2 polarization of microglia and confers brain inflammatory protection via the C/EBP-α pathway in intracerebral hemorrhage.

Microglia mediated inflammation contributes to intracerebral hemorrhage (ICH) induced secondary injury. Activated microglia has dual functions as pro-inflammatory (M1) and anti-inflammatory (M2) factors in brain injury and repair. MiR-124 is a potent anti-inflammatory agent which affects microglia after brain injury. However, the potential of modulating the M1/M2 polarization of microglia after ICH has not been reported. In this experiment, we detected the effect of miR-124 on the M1/M2 polarization state. In addition, the ability miR-124 to subsequently impacted neurological deficit and cerebral water content of ICH mice were studied. Furthermore, the relationship between miR-124 and C/EBP-α target was detected. We found that miR-124 significantly increased in M2-polarized microglia. Transduction of miR-124 mimics decreased proinflammatory cytokine levels. A coculture model of microglia and neuron indicated that M2-polarized microglia protected neuron damage. Furthermore, miR-124 banded to the 3-untranslated region of C/EBP-α and downregulated its protein levels. In vivo, infusion of miR-124 decreased brain levels of C/EBP-α and significantly reduced brain injury in ICH mice. Thus, miR-124 ameliorated ICH-induced inflammatory injury by modulating microglia polarization toward the M2 phenotype via C/EBP-α. MiR-124 regulatory mechanisms also might represent new therapeutic strategy in ICH.

IL-17A promotes microglial activation and neuroinflammation in mouse models of intracerebral haemorrhage.

Microglial activation is an important contributor to neuroinflammation in intracerebral haemorrhage (ICH). IL-17A has been demonstrated to be involved in neuroinflammatory diseases such as multiple sclerosis. However, the exact mechanism of IL-17A mediated microglial activation in ICH has not been well identified. The purpose of this experiment is to investigate the role of IL-17A in ICH induced microglial activation and neuroinflammation. ICH mice were made by injection of autologous blood model. IL-17A expression and inflammatory factors in perihematomal region, and neurological function of mice were examined after ICH. In addition, IL-17A-neutralizing antibody was utilized to potentially prevent microglial activation and neuroinflammation in ICH mice. The expression of IL-17A, inflammatory factors and microglial activation in perihematomal region were significantly increased, and neurological function of mice was impaired after ICH. In addition, IL-17A Ab prevented ICH-induced cytokine expression, including TNF-α, IL-1ß and IL-6, and downstream signaling molecules, including MyD88, TRIF, IκBα, and NF-κBp65 expression, and attenuated microglial activation. IL-17A Ab significantly reduced brain water content and improved neurological function of ICH mice. In conclusion, our results demonstrated that IL-17A was involved in ICH-induced microglial activation and neuroinflammation. IL-17A Ab might also provide a promising therapeutic strategy in ICH.