Progression Of Cerebral Infarction Research Articles

CircZfp609 contributes to cerebral infarction via sponging miR-145a-5p to regulate BACH1.

Circular RNAs (circRNA) have been reported to be involved in the progression of cerebral infarction. The purpose of this study was to reveal the role and potential molecular mechanism of circZfp609 (mmu_circ_0001797) in cerebral infarction. C57BL/6J mice was used to construct middle cerebral artery occlusion (MCAO) mice model, and primary mouse astrocytes were treated with oxygen-glucose deprivation/reperfusion (OGD/R) process. The circZfp609, microRNA (miR)-145a-5p and BTB and CNC homology 1 (BACH1) expression levels were detected by quantitative real-time PCR. Cell proliferation and apoptosis were assessed by cell counting kit 8 assay, EdU assay and flow cytometry. Western blot analysis was used to measure protein levels, and ELISA assay was utilized to detect the levels of inflammation factors. Lactate dehydrogenase (LDH) level was measured by LDH Assay Kit. Dual-luciferase reporter assay, RIP assay and RNA pull-down assay were used to evaluate RNA interaction. CircZfp609 was upregulated in MCAO mice and OGD/R-induced astrocytes. Knockdown of circZfp609 promoted cell proliferation, while suppressed apoptosis and inflammation in OGD/R-induced astrocytes. CircZfp609 served as a sponge for miR-145a-5p, and miR-145a-5p inhibitor reversed the regulation of circZfp609 knockdown on OGD/R-induced astrocyte injury. BACH1 was a target of miR-145a-5p, and its overexpression abolished the inhibition effect of miR-145a-5p on OGD/R-induced astrocyte injury. Besides, circZfp609 downregulation also relieved the brain injury of MCAO mice through miR-145a-5p/BACH1 axis. Our data showed that circZfp609 might promote cerebral infarction by regulating the miR-145a-5p/BACH1 pathway.

Microglia drive transient insult-induced brain injury by chemotactic recruitment of CD8+ T lymphocytes

The crosstalk between the nervous and immune systems has gained increasing attention for its emerging role in neurological diseases. Radiation-induced brain injury (RIBI) remains the most common medical complication of cranial radiotherapy, and its pathological mechanisms have yet to be elucidated. Here, using single-cell RNA and Tcell receptor sequencing, we found infiltration and clonal expansion of CD8+ T lymphocytes in the lesioned brain tissues of RIBI patients. Furthermore, by strategies of genetic or pharmacologic interruption, we identified a chemotactic action of microglia-derived CCL2/CCL8 chemokines in mediating the infiltration of CCR2+/CCR5+ CD8+ Tcells and tissue damage in RIBI mice. Such a chemotactic axis also participated in the progression of cerebral infarction in the mouse model of ischemic injury. Our findings therefore highlight the critical role of microglia in mediating the dysregulation of adaptive immune responses and reveal a potential therapeutic strategy for non-infectious brain diseases.

Heterogeneity evaluation of multi-high b-value apparent diffusion coefficient on cerebral ischemia in MCAO rat.

To assess brain damage in a rat model of cerebral ischemia based on apparent diffusion coefficient (ADC) data obtained from multi-high b-values and evaluate the relationship between Aquaporin 4 (AQP4) expression and ADC. Thirty eight male Sprague-Dawley rats were randomized into two groups: (1) sham controls (n = 6) and (2) cerebral ischemia (successful model, n = 19). All rats underwent diffusion-weighted imaging (DWI) with both standard b-values and multi-high b-values (2,500-4,500 s/mm2) using a 3.0-T device. Standard ADC (ADCst) maps and multi-high b-value ADCs (ADCmh) were calculated, respectively. Aquaporin 4 expression was quantified using Western blot. Relative values of ADCst and ADCmh, AQP4 expression were compared between the sham group and the ischemia group. Correlations between ADC values and AQP4 expression were evaluated. At 0.5 h after suture insertion, the value of ADCmh on the lesion was obviously decreased, and there was no difference in lesion volume when compared with ADCst. After reperfusion, besides similar regions where ADCst values decreased, we also found additional large values on ADCmh within the cortex of the ipsilateral side or surrounding the lesion. The lesion evolution of the large value on ADCmh was quite different from other indicators. But the total ADCmh values were still significantly associated with ADCst. The AQP4 protein expression level was appreciably increased after middle cerebral artery occlusion (MCAO), but there was no correlation between AQP4 expression either with ADCmh or ADCst. We found the large values on ADCmh during the progression of cerebral infarction is varied, but there was no correlation between ADCmh values and AQP4 expression. ADCmh may indicate the heterogeneity of ischemia lesions, but the underlying pathological basis should be further explored.

Progression of cerebral infarction before and after thrombectomy is modified by prehospital pathways

BackgroundEvidence of the consequences of different prehospital pathways before mechanical thrombectomy (MT) in large vessel occlusion stroke is inconclusive. The aim of this study was to investigate the infarct extent...

MiR-203 Targets to the 3'-UTR of SLUG to Suppress Cerebral Infarction-Induced Endothelial Cell Growth and Motility.

Cerebral infarction is one of the leading causes of death worldwide, in which angiogenesis plays a critical role. On the other hand, accumulating evidence has demonstrated that microRNAs (miRNAs) function as key modulators in the formation and progression of cerebral infarction. However, the molecular mechanisms of miRNAs underlying cerebral infarction-associated angiogenesis remain unclear. In the present study, we indicated that the expression of miR-203 was significantly downregulated in serum samples derived from patients with cerebral infarction and in mice brain samples following middle cerebral artery occlusion (MCAO) compared with healthy controls. In vitro, the expression of miR-203 was obviously downregulated in hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs). Functionally, ectopic expression of miR-203 drastically suppressed HUVEC proliferation, invasion, and migration. In addition, SLUG, a zinc finger transcriptional repressor, was identified as a direct target of miR-203 and was negatively correlated with miR-203 expression in MCAO mice and in hypoxia-induced HUVECs. Furthermore, overexpression of SLUG reversed the inhibitory effect of miR-203 on proliferation, invasion, and migration abilities of HUVECs. Taken together, our research provides a novel insight of the miR-203-SLUG axis into cerebral infarction-associated endothelial behaviors and may offer a powerful therapeutic target of cerebral ischemia.

Prazosin blocks apoptosis of endothelial progenitor cells through downregulating the Akt/NF-κB signaling pathway in a rat cerebral infarction model.

Endothelial progenitor cells (EPCs) can enhance the recanalization of thrombosis during the progression of cerebral infarction. Prazosin plays a therapeutic role in expanding the peripheral vasculature and regulating infarction cardiosclerosis by inhibiting phosphoinositide signaling. However, the possible mechanisms underlying the therapeutic effects of prazosin have not been fully explored. The purpose of the present study was to analyze the anti-apoptotic effects of prazosin on EPCs in a rat cerebral infarction model. The results showed that prazosin treatment decreased apoptosis of EPCs. Prazosin treatment decreased the serum expression levels of the inflammatory factors, interleukin-1β and tumor necrosis factor-α in rats with cerebral infarctions as well as in EPCs in vitro. In addition, prazosin reduced the expression levels of Akt, NF-κB, phosphorylated (p)-Akt and p-NF-κB in EPCs and the middle cerebral artery of rats with cerebral infarction. These findings demonstrated that prazosin inhibited EPC apoptosis in the cerebral infarction rats through targeting the Akt/NF-κB signaling pathway. In conclusion, these results indicated that prazosin has a preventive effect on cerebral infarction by inhibiting EPC apoptosis and by inhibiting the inflammatory response in vitro and in vivo through regulating the Akt/NF-κB signaling pathway.

Serum miR-133 as a Potential Biomarker in Acute Cerebral Infarction Patients.

The study explores the expression and significance of miR-133 expression in peripheral blood of patients with acute cerebral infarction (ACI), so as to provide new evidence for the diagnosis and treatment of ACI. Serum levels of miR-133, interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) were examined using RT-PCR and ELISA, respectively. Pearson's correlation assay was used to analyze the relationship between the level of serum miR-133 and inflammatory factors. Kaplan-Meier method was used to analyze the 10-year survival rate of ACI patients with different levels of miR-133 expression. The level of serum miR-133 in the ACI group was significantly higher than that in healthy group. Mean-while, the level of serum miR-133 in the large infarction group, middle infarction group, small infarction group, and lacunar infarction group was higher than in the healthy group. Moreover, the serum levels of miR-133 in patients with atherosclerotic thrombotic cerebral infarction (AT) and cardioembolic stroke (CE) were significantly higher than those in healthy subjects and small artery occlusive cerebral infarction (SAD) subjects. Serum levels of IL-6, IL-8, CRP and TNF-α in ACI group were significantly higher than those in healthy group. The correlation analysis showed that serum miR-133 was positively correlated with IL-6, IL-8, CRP, and TNF-α in ACI patients. The 10-year survival rate of the low-expression group was significantly higher than that of the high-expression group. Serum level of miR-133 may indicate the onset and progression of cerebral infarction and may be a potential biomarker for the diagnosis of ACI.

Homocysteine, interleukin-1β, and fasting blood glucose levels as prognostic markers for diabetes mellitus complicated with cerebral infarction and correlated with carotid intima-media thickness.

Diabetes mellitus complicated with cerebral infarction (DMCI) has a high incidence and disability rate. Therefore, identification of biomarkers for the early prediction of the development and progression of cerebral infarction (CI) is of great significance for the prevention and treatment of this disease. The roles of serum homocysteine (Hey), interleukin-1β (IL-1β), and fasting blood glucose (FBG) in DMCI and their correlations with carotid intima-media thickness (CIMT) were explored. A total of 124 patients with DMCI (DMCI group) and 103 patients with diabetes mellitus (DM) (DM group) admitted to the People's Hospital of Liuhe District of Nanjing were enrolled in this study. A further 100 healthy controls undergoing physical examinations during the same period (HC group) were also enrolled. CIMT value was detected by carotid artery ultrasound. Hey and FBG levels were determined by a fully automatic biochemical analyzer. The IL-1β level was detected by enzyme-linked immunosorbent assay (ELISA). The levels of Hey, IL-1β, and FBG and the CIMT value in the DMCI and DM groups were significantly higher than those in the HC group (P<0.001). The levels and the value in the DMCI group were significantly higher than those in the DM group (P<0.001). Hey, IL-1β, and FBG levels were positively correlated with CIMT value (r=0.542, P<0.001; r=0.522, P<0.001; r=0.402, P<0.001). Receiver operating characteristic (ROC) curves showed that the sensitivity and specificity of Hey for diagnosing DMCI were 86.29 and 80.58%; those of IL-1β were 68.55 and 86.41%; those of FBG were 69.35 and 88.35%. Multivariate logistic regression analysis revealed that systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), Hey, IL-1β, FBG, and CIMT were independent risk factors for DMCI (P<0.05). In conclusion, patients with DMCI have severe atherosclerosis. Hey, IL-1β, and FBG are involved in the development and progression of DMCI, so they can be used as predictive markers for the disease. Hey, IL-1β, FBG, and CIMT are independent risk factors for patients with DMCI.

Interaction between Urinary 11 Dehydrothromboxane B2 and Some Other Risk Factors in the Occurrence of Cerebral Infarction

Objective:The objective of this study is to analyze the interaction between the urinary 11-dehydrothromboxane B2 (11-DH-TXB2) content and the smoking, drinking, hypertension or diabetes history of patients with cerebral infarction, and to determine the value of 11-DH-TXB2 in the occurrence and prevention of cerebral infarction.Methods:117 patients with cerebral infarction and 50 healthy controls were selected. Their general information, including smoking, drinking, hypertension and diabetes history, was analyzed, and their urinary11-DH-TXB2 contents were measured. The difference in the urinary 11-DH-TXB2 content between the two groups, and the additive model of the interaction between the urinary 11-DH-TXB2 content and other risk factors of cerebrovascular diseases were statistically analyzed.Results:There was no significant difference in the general information between the two groups (P&gt; 0.05). Significant differences were observed in the urinary 11-DH-TXB2 content, and the smoking, diabetes and hypertension history between the two groups, while there was no significant difference in the drinking history between the two groups. The analysis of the interaction additive model showed that the OR value was 1, the synergy index (S) of increased 11-DH-TXB2 and smoking history was 1.219, the S of increased 11-DHTXB2 and hypertension history was 5.578 and that of increased 11-DH-TXB2 and the diabetes history was 4.604.Conclusion:There is a correlation between the urinary 11-DH-TXB2 content and the occurrence of cerebral infarction, and there is a synergistic interaction between the urinary DH-TXB2 content and the smoking, hypertension or diabetes history of patients with cerebral infarction. The increased 11-DH-TXB2 may be a risk factor for cerebral infarction and the urinary 11-DHTXB2 content can be used as an index to predict the occurrence and progression of cerebral infarction.

Significance of decreased serum interleukin-10 levels in the progression of cerebral infarction.

Anti-inflammatory cytokine and its serological detection may have an important role in the process of cardiovascular and cerebrovascular diseases. We investigated whether serum interleukin-10 (IL-10) is associated with cerebral infarction or not in the general population. Identified comprehensive searching was performed covering PubMed, EMBASE, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine, and China National Knowledge Infrastructure databases. Two reviewers extracted data and assessed studies independently. Information was extracted separately and classed into Asians and Caucasians. Summary standardized mean differences (SMDs) with 95% confidence intervals (CI) were used with the utilization of Z test. Nine studies ranged from 2003 to 2014 were collected for meta-analysis. Results identified a negative association between serum IL-10 levels and cerebral infarction (SMD=1.80, 95% CI 0.79-2.81, P<0.001). Country-subgroup analysis showed that low IL-10 level may be the main risk factor for cerebral infarction in India (SMD=1.44, 95% CI 1.13-1.75, P<0.001) and Croatia (SMD=2.96, 95% CI 2.48-3.44, P<0.001). In the ethnicity-stratified subgroup analysis, serum IL-10 levels were negatively correlated with cerebral infarction in Asians (SMD=2.52, 95% CI 0.47-4.57, P=0.016), while not in Caucasians (P>0.05). The lower serum IL-10 concentration was significantly associated with an increased likelihood of cerebral infarction in this meta-analysis. More prospective studies should be conducted to provide stronger evidence justifying the use of IL-10 as new biomarker to identify a predisposition toward cerebral infarction.

Genetic polymorphisms in the ESR1 gene and cerebral infarction risk: a meta-analysis.

A number of studies have documented that estrogen receptor α (ESR1) may play an important role in the development and progression of cerebral infarction, but many existing studies have yielded inconclusive results. This meta-analysis was performed to evaluate the relationships between ESR1 genetic polymorphisms and cerebral infarction risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1, 2013, without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Seven case-control studies were included with a total of 1471 patients with cerebral infarction and 4688 healthy control subjects. Two common single-nucleotide polymorphisms (SNPs) in the ESR1 gene (rs2234693 T>C and rs9340799 A>G) were assessed. Our meta-analysis results revealed that ESR1 genetic polymorphisms might increase the risk of cerebral infarction. Subgroup analysis by SNP type indicated that both rs2234693 and rs9340799 polymorphisms in the ESR1 gene were strongly associated with an increased risk of cerebral infarction. Further subgroup analysis by ethnicity showed significant associations between ESR1 genetic polymorphisms and increased risk of cerebral infarction among both Asians and Caucasians. In the stratified subgroup analysis by gender, the results suggested that ESR1 genetic polymorphisms were associated with an increased risk of cerebral infarction in the female population. However, there were no statistically significant associations between ESR1 genetic polymorphisms and cerebral infarction risk in the male population. Meta-regression analyses also confirmed that gender might be a main source of heterogeneity. Our findings indicate that ESR1 genetic polymorphisms may contribute to the development of cerebral infarction, especially in the female population.

Anticoagulant Treatment to Prevent Cerebral Infarction

The indications for anticoagulant treatment to prevent cerebral infarction or progression of cerebral infarction are now clear. The indications are: (1) Prevention of recurrent embolization from a cardiac source (long-term anticoaguland treatment). (2) Transient ischemic attacks (particularly vertebrobasilar system) if a surgically accessible causative lesion, polycythemia, and thrombocytosis are not present (anticoagulants for a few months.) (3) Progressing stroke in either systme assuming that the neurological defect is partial and CT scan shows no evidence of bleeding (anticoagulants for a few months.) (4) Rarely, completed stroke (long-term).

Brain serotonin after experimental vascular occlusion.

Unilateral ligation of a common carotid artery in gerbils causes a decreased rate of serotonin synthesis and degradation but an increased release of this monoamine. In the brain, reduction of cerebral serotonin content during ischemia is followed by accumulation of its main metabolite, 5-hydroxyindolacetic acid. These data support the contention that serotonin plays an important role in the progression of cerebral infarction.