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Objective:To investigate the effect of pioglitazone on white matter injury after cerebral ischemia-reperfusion in mice and its mechanism.Methods:Forty-two young male C57BL/6J mice were randomly divided into sham operation group, model group, and pioglitazone group ( n=14 in each group). The model of cerebral ischemia-reperfusion was induced by transient middle cerebral artery occlusion with suture-occluded method. On the 3 rd and 7 th day after the establishment of the model, the neural function was assessed by the adhesive removal test. The mice were killed on the 7 th day after the establishment of the model. HE staining was used to detect the extent of cerebral infarction. Immunofluorescence staining and Western blot analysis were used to detect the degree of white matter damage and the changes of microglia phenotype. Results:On the 7 th day after cerebral ischemia-reperfusion, the adhesive removal time in the PGZ group was significantly shortened compared with the model group ( P<0.05), the percentage of cerebral infarction volume was significantly reduced ( P<0.05), the ratio of MBP/NF200 fluorescence intensity in the cortical and striatal areas was significantly increased (all P<0.05), and the number of CD16 +/Iba1 + microglia was significantly decreased ( P<0.01), while the number of CD206 +/Iba1 + microglia tended to increase, but there was no statistical difference. Conclusion:Pioglitazone may reduce the degree of white matter injury and nerve function damage in mice with cerebral ischemia-reperfusion, and its mechanism may be associated with regulating the transformation of microglia from M1 type to M2 type.
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Objective:To explore the possible mechanism of exacerbation of anxiety-like behavior in db/db mice after distal middle cerebral artery occlusion (dMCAO).Methods:The db/db mice was used to establish a type 2 diabetes mellitus model. Meanwhile, heterozygous db/+ mice and C57 wild-type (WT) mice were chosen as double control groups. Then a permanent distal middle cerebral artery occlusion model was employed as an acute ischemic stroke model. The blood glucose levels before and post-dMCAO surgery on day1, day3, and day5 were detected. The brain tissue loss at 35 days after stroke was measured by immunofluorescent staining of MAP2. The open-field test was performed to estimate anxiety-like behavior and general motor and exploring ability of the animals. Axons and myelin were immunostained with non-phosphorylated neurofilaments (SMI32) and myelin basic protein (MBP), respectively, to evaluate differences in white matter integrity in WT, db/+ and db/db mice 35 days after stroke. The correlation between SMI32/MBP and open field test parameters (time in center and corner) was analyzed. Flow cytometry was employed to detect the amount of T cells and B cells, including regulatory T cells (Tregs) in the brain tissue.Results:Blood glucose levels in db/db mice were significantly higher than db/+ mice and WT mice in both sham and dMCAO groups ( P<0.01). There was no significant difference in brain tissue loss 35 days post-stroke among db/db mice, db/+ mice, and WT mice. In the open field test, there were significant differences in the total distance of db/db mice, db/+ and WT mice in the sham and dMCAO groups. Db/db mice shorter than db/+ mice ( P<0.05), WT mice ( P<0.01), and db/+ mice shorter than WT mice ( P<0.05). There were significant time differences in the center among db/db, db/+, and WT mice in sham and dMCAO groups. In both the sham and dMCAO groups, db/db mice spent less time in the center area of the open field than WT mice ( P<0.01). In the sham group, db/+ mice spent less time in the center area than WT mice ( P<0.05). In dMCAO group, db/db mice spent less time in the center area than db/+mice ( P<0.05), and db/+ mice spent less time in the center area than WT mice ( P<0.01). For the time in the corner, in both the sham and dMCAO groups, db/db mice and db/+ mice consumed more time than WT mice ( P<0.01 or <0.05). In the dMCAO group, db/db mice spent more time in the corner than db/+ mice ( P<0.05). Referring to white matter injury, an increased SMI32/MBP ratio in EC area and CTX area (data was not shown in this article) after dMCAO in db/db, db/+ and WT mice were detected. In EC area, db/db mice have a higher SMI32 ratio than db/+ mice and WT mice: 4.24 ± 0.37 vs. 1.96 ± 0.37, 1.80 ± 0.36, both have significant differences ( P<0.01). For db/db mice and WT mice, the SMI32/MBP ratio negatively correlates with time in center and positive correlation with time in the corner. Three days after dMCAO, the total cells of CD 3+ T cells, CD 8+ cells, Tregs, in db/db mice group have significantly decreased compared to WT group: 4 079 ± 1 345 vs. 70 055 ± 3 374, 141.30 ± 28.36 vs. 2 714.00 ± 463.20, 148.00 ± 61.15 vs. 3 007.00 ± 639.90 ( P<0.01), while B cell has no change between two groups. Conclusions:By comparing the severity of anxiety-like behavior of db/db mice, the severity of white matter injury, and the number of T cells and B cells in brain tissue after dMCAO, immune-mediated brain white matter injury may aggravate db/db mice′s post-dMCAO anxiety-like behavior. Due to the gene dose effect, db/+ mice are not suitable as a control group for db/db mice in animal experiments involving anxiety-like behavior assessment.
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Objective:To investigate the influence of Covid-19 epidemic on the number of acute ischemic stroke patients with intravenous thrombolytic therapy in Dalian in 2020, the way to hospital, onset to door time (ODT), door to needle time(DNT), onset to needle time(ONT), and the National Institute of Health Stroke Scale (NIHSS) before and after intravenous thrombolytic therapy.Methods:This was a retrospective descriptive study on 13 map-participating hospitals in Dalian from August 2020 to December 2020. The number of acute ischemic stroke patients with intravenous thrombolytic therapy, ODT, DNT, ONT, modes of transport to hospital, the NIHSS score before and after intravenous thrombolytic therapy, etc were analyzed. Data were collected from August 1, 2020 to December 31, 2020, and compared with the baseline data from the same period in 2019.Results:SPSS 22.0 statistical software and Data Analysis ToolPak were used for statistical analysis of the obtained data, and T tests statistic was used for data analysis. In 2020,the number of acute ischemic stroke patients with intravenous thrombolytic therapy increased (681 cases vs 416 cases), and DNT increased [50 minutes vs 45 minutes P = 0.01]. In 2020, 83.55% of patients indicated self-visit as their main mode of transport to the hospital. In 2020, among the self-visit patients with NIHSS score<15 scores,the number of the patients with the NHISS score unchanged or decreased after intravenous thrombolytic therapy was more (562 scores vs. 535 scores, P<0.001), and the patients with NIHSS score ≥15 scores were more willing to call ambulances to hospital. Conclusions:During the Covid-19 epidemic period of 2020, the number of acute ischemic stroke patients receiving intravenous thrombolytic therapy increased, DNT increase; the patients withNIHSS score<15 scores are more willing to choose to visit the hospital using their own transportation and benefit from intravenous thrombolytic therapy. The patients with NIHSS ≥15 scores prefer to call ambulances to hospital.
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0.05).In group I,the mRNA levels of Ang-1 were lower than those in group C during 3-6 h after onset of ischemia(P