Relationship between morning blood pressure variability and cerebral microbleed burden in patients with hypertension.

Cerebral microbleeds (CMBs) can be understood as a type of target organ damage caused by hypertension. We aimed to explore the association of the CMB burden with morning blood pressure (BP) variability in patients with hypertension. We divided patients with hypertension into two groups: a group with 1-10 CMBs and a group with more than 10 CMBs. The duration, grade, medication, and control of hypertension were recorded in all patients. Morning home BP measurements were performed every 3 days for a month. A total of 791 patients were recruited. Full factor model analysis showed that higher morning home diastolic BP variability (standard deviation [SD], OR = 1.080, 95% CI: 1.024-1.140, P = .005; coefficient of variation [CV], OR = 1.076, 95% CI: 1.028-1.128, P = .002) was associated with more than 10 CMBs. Morning home systolic and diastolic blood pressure variability (SD, CV, average real variability) in more than 10 non-lobar CMBs group was significantly higher than that in 1-10 non-lobar CMBs group (P < .05).The multivariate analysis showed higher morning home diastolic blood pressure variability (SD, OR = 1.124, 95% CI: 1.031-1.224, P = .008; CV, OR = 1.099, 95% CI: 1.019-1.186, P = .015; average real variability, OR = 1.055, 95% CI: 0.995-1.120, P = .075) was associated with more than 10 non-lobar CMBs. There was no significant relationship between morning home systolic blood pressure variability and more than 10 non-lobar CMBs (P > .05). Higher morning home diastolic blood pressure variability was associated with more than 10 CMBs and more than 10 non-lobar CMBs.

Leptin ameliorates Aß1-42-induced Alzheimer's disease by suppressing inflammation via activating p-Akt signaling pathway.

Background: Alzheimer's disease (AD) is characterized by progressive neuronal loss, cognitive disorder, and memory decline. Leptin has been reported to have a neuroprotective effect on neurodegenerative diseases. Objective: Our aim was to investigate whether intraperitoneal injection of leptin has a neuroprotective effect and to explore its underlying mechanisms in the AD mouse model. Methods: Aß1-42 was injected into male C57BL/6J mice to construct an AD mouse model, and leptin was injected intraperitoneally to cure AD. The Morris water maze test was used to investigate spatial learning ability. Neuronal loss was tested by tyrosine hydroxylase expression in the hippocampus, and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling assay was applied to detect neuronal apoptosis. Pro-inflammatory cytokine levels were monitored by RT-PCR and western blotting was selected to explore which signaling pathway leptin acted on. Results: Leptin ameliorated spatial learning impairment, restored neuronal loss and apoptosis, and inhibited pro-inflammatory cytokine expression by activating the p-Akt signaling pathway in Aß1-42-induced AD mice. Conclusion: Leptin ameliorates Aß1-42-induced AD by suppressing inflammation via activating the p-Akt signaling pathway.

Clinical Prediction Model for Screening Acute Ischemic Stroke Patients With More Than 10 Cerebral Microbleeds.

Background: Hemorrhagic transformation is one of the most serious complications in intravenous thrombolysis. Studies show that the existence of more than 10 cerebral microbleeds is strongly associated with hemorrhagic transformation. The current study attempts to develop and validate a clinical prediction model of more than 10 cerebral microbleeds. Methods: We reviewed the computed tomography markers of cerebral small vessel diseases and the basic clinical information of acute ischemic stroke patients who were investigated using susceptibility weighted imaging from 2018 to 2021. A clinical prediction model of more than 10 cerebral microbleeds was established. Discrimination, calibration, and the net benefit of the model were assessed. Finally, a validation was conducted to evaluate the accuracy and stability of the model. Results: The multivariate logistic regression model showed hypertension, and some computed tomography markers (leukoaraiosis, lacunar infarctions, brain atrophy) were independent risk factors of more than 10 cerebral microbleeds. These risk factors were used for establishing the clinical prediction model. The area under the receiver operating characteristic curve (AUC) was 0.894 (95% CI: 0.870-0.919); Hosmer-Lemeshow chi-squared test yielded χ2 = 3.946 (P = 0.862). The clinical decision cure of the model was higher than the two extreme lines. The simplified score of the model ranged from 0 to 12. The model in the internal and external validation cohort also had good discrimination (AUC 0.902, 95% CI: 0.868-0.937; AUC 0.914, 95% CI: 0.882-0.945) and calibration (P = 0.157, 0.247), and patients gained a net benefit from the model. Conclusions: We developed and validated a simple scoring tool for acute ischemic stroke patients with more than 10 cerebral microbleeds; this tool may be beneficial for paradigm decision regarding intravenous recombinant tissue plasminogen activator therapy of acute ischemic stroke.

Downregulation of microRNA­451 improves cell migration, invasion and tube formation in hypoxia­treated HUVECs by targeting MIF.

Angiogenesis is a critical process of recovery from cerebrovascular disease. A growing body of evidence has confirmed that microRNAs (miRNAs/miRs) have an important role in the modulation of angiogenesis under physiological and pathological conditions including cerebral ischemia injury (CII). Therefore, the aim of the present study was to explore the function and mechanism of microRNAs in regulating angiogenesis using a cell model of CII. Firstly, a miRNA microarray was performed to analyze miRNA expression in serum samples from patients with cerebral ischemia and the results revealed that miR­451 was one of the miRNAs that was the most significantly downregulated. Subsequently, human umbilical vein endothelial cells (HUVECs) were used as an in vitro model to further explore the mechanisms governing angiogenesis during hypoxia. The results demonstrated that overexpression of miR­451 had a significantly anti­angiogenic effect by suppressing tube formation, migration and wound healing in vitro. By contrast, reducing the expression of miR­451 promoted HUVEC migration and tubulogenesis under normoxic conditions. The present study further identified that macrophage migration inhibitory factor (MIF), an important angiogenic regulator, was a novel target of miR­451 that could reverse the effects of miR­451 on the regulation of angiogenesis in HUVECs under hypoxic or normoxic conditions. These results revealed that downregulation of miR­451 promotes angiogenesis by targeting MIF in hypoxic HUVECs and indicated that miR­451 is a potential candidate for CII therapeutics.