Effects of ischemia-hypoperfusion on neuro-vascular units in dual transgenic mice with Alzheimer's disease.

INTRODUCTION: The study aimed to investigate the effects of ischemia on neuro-vascular units in transgenic mice, and to investigate the role of ischemia-hypoperfusion in the model of dual transgenic mice with dementia. MATERIAL AND METHODS: In this study, the ischemic model was generated by operating a bilateral common carotid artery micro-embolism. Mice were divided into four groups, including group 1: C57BL sham surgery group (control), group 2: C57BL ischemic group, group 3: amyloid precursor protein/presenilin-1 (APP/PS1) group, and group 4: APP/PS1 ischemic group. Each group comprised 20 mice. Spatial behavior and memory ability of mice were detected by Morris water maze and jumping platform test. Mouse hippocampus was observed by HE staining and Congo red staining. Ultrastructure of each group of neuro-cyclic units was observed by electron microscopy. Various biochemical indicators were detected by ELISA. Western blot detected the amount of protein expression. qRT-PCR identified mRNA expression. RESULTS: The results indicated that learning and memory functions of C57 ischemic mice were lower than those of control group. Positive expression area of APP in APP/PS1 ischemic group was higher than in APP/PS1 group. In APP/PS1 group and APP/PS1 ischemic group, the content of Ab was significantly higher than in C57 ischemic group. Electron microscopic observation revealed that there were more mitochondrial vacuoles in hippocampal neurons of APP/PS1 mice, and the structure was relatively intact. Mitochondrial vacuoles in hippocampus increased significantly, and vascular wall proliferated in APP/PS1 ischemic group. Compared with C57 control group, the content of vascular endothelial growth factor (VEGF) increased significantly in C57 ischemic group. CONCLUSIONS: Ischemia deteriorates the learning and memory function of transgenic mice, aggravates the damage of neuro-vascular units, and impairs the blood-brain barrier transport of Ab, leading to an increase in the concentration of Ab cerebrospinal fluid, and further deterioration of neuro-vascular units. At the same time, ischemia is an effective stimulating factor in the release of VEGF.

[Outcomes in randomized controlled trials of acupuncture for vascular cognitive impairment during recent five years].

The existing problems in the outcomes of randomized controlled trials (RCTs) of acupuncture for vascular cognitive impairment (VCI) during recent five years are analyzed and suggestions are proposed. The RCTs of acupuncture for VCI were selected in PubMed, EMbase, Cochrane Library, Clinical Trials, CNKI database, Wanfang database, VIP database, SinoMed database and Chinese Clinical Trial Registry (ChiCTR) from January 1, 2015 to September 14, 2020. The outcomes were extracted and analyzed. As a result, 21 RCTs were included and the outcomes used were divided into 9 categories: clinical symptom/sign indexes, quality of life indexes, neuroimaging indexes, neuroelectrophysiology indexes, blood biochemical indexes, hemorheology indexes, TCM syndrome score indexes, clinical efficacy indexes, and safety indexes. Among them, the top three of the most used outcomes were clinical symptoms/signs indexes (21, 100.0%), clinical efficacy indexes (14, 66.7%) and quality of life indexes (12, 57.1%). In the RCTs of acupuncture for VCI, attention should be paid to distinguish the primary outcomes and secondary outcomes, adopt objective and standardized efficacy evaluation, and give consideration to report the outcomes of safety, health economic and TCM characteristic indexes.

[Overview of systematic reviews of acupuncture for vascular cognitive impairment].

OBJECTIVE: To overview the methodological quality, report quality and evidence quality of the systematic review (SR) of acupuncture for vascular cognitive impairment ( VCI ). METHODS: The SRs regarding acupuncture for VCI were searched in PubMed, Cochrane Library, EMbase, CNKI, SinoMed, Wanfang and VIP databases. The retrieval period was from the establishment of the database to September 24, 2020. The report quality, methodological quality and evidence quality of the included SRs were evaluated by PRISMA statement, the AMSTAR 2 tool and the GRADE system. RESULTS: A total of 22 SRs were included, including 102 outcome indexes. The methodological quality was generally low, with low scores on items 2, 5, 7, 10, 14, 15 and 16. The report quality was good, with scores ranging from 19 points to 24.5 points. The problems of report quality were mainly reflected in the aspects of structural abstract, program and registration, other analysis and funding sources. The level of outcome indexes of SRs was mostly low or very low, and the main leading factor was limitation, followed by inconsistency and inaccuracy. CONCLUSION: Acupuncture for VCI is supported by low quality evidence of evidence-based medicine, but the methodological quality and evidence body quality of relevant SRs are poor, and the standardization is needed to be improved.

EGb in the Treatment for Patients with VCI: A Systematic Review and Meta-Analysis.

BACKGROUND: Ginkgo biloba extract (EGb) is widely used to treat impairments in memory, cognition, activities of daily living, inflammation, edema, stroke, Alzheimer's dementia, and aging. AIM: We aimed to evaluate the safety and efficacy of EGb in treating vascular cognitive impairment (VCI). METHODS: The systematic review was performed using the latest guidelines. We searched for EGb-related trials up to March 1, 2021, in four Chinese databases, three English databases, and clinical trial registry platforms. Randomized controlled trials (RCTs) were included if the study enrolled participants with VCI. Two reviewers independently extracted the data and critically appraised the study quality. Heterogeneity was quantified with I 2. Both sensitivity and subgroup analyses were used to identify the sources of heterogeneity. Publication bias was assessed with funnel plots. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to rate the evidence quality. Outcomes included assessments using the Activities of Daily Living (ADL), Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Hasegawa Dementia Scale (HDS), Barthel Index (BI), Functional Activity Questionnaire (FAQ), and adverse events. RESULTS: In this study, a total of 2019 patients in 23 RCTs were included. EGb appeared to be more effective than control conditions as assessed by the results of cognitive function evaluation, including MMSE (MDMMSE,EGb vs.blank = 3.04, 95% CI: 0.10-5.98; MDMMSE,EGb vs.drugs for VCI = 2.70, 95% CI: 1.39-4.01; MDMMSE,EGb+drugs for VCI vs.blank = 5.90, 95% CI: 4.21-7.59; and MDMMSE,EGb+drugs for VCI vs.drugs for VCI = 3.14, 95% CI: 2.14-4.15), MoCA (MDMoCA,EGb vs.blank = 5.30, 95% CI: 2.15-8.46; MDMoCA,EGb+drugs for VCI vs.blank = 2.66, 95% CI: 1.82-3.50; and MDMoCA,EGb+drugs for VCI vs.drugs for VCI = 2.56, 95% CI: 1.85-3.27), HDS (MDHDS,EGb vs.blank = 6.50; 95% CI: 4.86-8.14; MDHDS,EGb+drugs for VCI vs.drugs for VCI = 3.60, 95% CI: 2.50-4.70), ADL (MDADL,EGb vs.blank = 7.20, 95% CI: 3.28-11.12; MDADL,EGb+drugs for VCI vs.blank = 10.00, 95% CI: 7.51-12.49; and MDADL,EGb+drugs for VCI vs.drugs for VCI = 9.20, 95% CI: 7.26-11.14), BI (MDBI,EGb+drugs for VCI vs.drugs for VCI = 5.71, 95% CI: 2.99-8.43; MDFAQ,EGb vs.drugs for VCI = -1.43, 95% CI: -2.78 to 0.08), and FAQ (MDFAQ,EGb+drugs for VCI vs.drugs for VCI = -2.17, 95% CI: -4.13 to 0.21). Evidence of certainty ranged from medium certainty to very low certainty. CONCLUSION: This meta-analysis showed that EGb may be an effective and safe treatment in improving MMSE, MOCA, ADL, and BI for VCI patients within three months of diagnosis. However, given the quality of the included RCTs, more preregistered trials are needed that explicitly examine the efficacy of EGb. This systematic review has been registered on PROSPERO, with the registration number CRD42021232967.