Current neurovascular research最新文献

Background: Dual Specificity Phosphatase 3 (DUSP3) regulates the innate immune response and is associated with ischemia/reperfusion (I/R). However, the precise function of DUSP3 in acute myocardial infarction (AMI) remains to be established.

Methods: In this study, the AMI model in vivo was established in mice by permanent left anterior descending coronary artery (LAD) occlusion, and primary neonatal mouse cardiomyocytes were treated with hypoxia for 12 hours to mimic AMI in vitro. Sh-DUSP3 and AAV9-sh-DUSP3 were used to knock down the DUSP3 expression. LVEF%, LVFS%, SOD1, and HO-1 level, and TTC staining were used to test the cardiac function. Flow cytometric analysis, Western blot, and TUNEL staining were used to investigate the effect of DUSP3 knockdown on apoptosis. Moreover, we detect inflammatory factors expression and oxidative stress by ELISA. Besides, we investigate DUSP3 expression by RT-qPCR.

Results: Our findings determined the role of DUSP3 in the progression of AMI. And demonstrated that DUSP3 knockdown alleviated oxidative stress, inflammation, and apoptosis. In addition, our results indicated that DUSP3 knockdown could regulate the expression of p-NF-κB, ICAM1, and VCAM1.

Conclusion: Our results demonstrated that the knockdown of DUSP3 could effectively alleviate AMI symptoms and be mediated through the NF-κB signaling pathway.

Background: Physical activity in Amyotrophic Lateral Sclerosis (ALS) plays a controversial role. In some epidemiological studies, both recreational or professional sport exercise has been associated to an increased risk for ALS but the mechanisms underlying the effects of exercise have not been fully elucidated in either patients or animal models.

Methods: To better reproduce the influence of this environmental factor in the pathogenesis of ALS, we exposed SOD1^G93A low-copy male mice to multiple exercise sessions at asymptomatic and pre-symptomatic disease stages in an automated home-cage running-wheel system for about 3 months.

Results: Repeated voluntary running negatively influenced disease progression by anticipating disease onset, impairing neuromuscular transmission, worsening neuromuscular decline, and exacerbating muscle atrophy. Muscle fibers and neuromuscular junctions (NMJ) as well as key molecular players of the nerve-muscle circuit were similarly affected.

Conclusion: It thus appears that excessive physical activity can be detrimental in predisposed individuals and these findings could model the increased risk of developing ALS in predisposed and specific professional athletes.

Background: Through an analysis of the risk factors associated with patent foramen ovale (PFO)-related stroke (PS), we aimed to modify the Risk of Paradoxical Embolism (RoPE) to assess the risk of PS.

Methods: A retrospective collection of ischemic stroke (IS) patients with PFO admitted to the Department of Neurology at Beijing Chaoyang Hospital was conducted. The patients were classified into PS and non-PS groups. PS risk factors and RoPE scoring were analyzed based on clinical data, laboratory indicators, and imaging data. Independent risk factors were incorporated into the RoPE scoring system for enhancement.

Results: Significant differences were observed between the two groups regarding total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and uric acid levels. The transverse diameter of the left atrium was significantly larger in the non-PS group compared to the PS group. Multivariate logistic regression revealed that higher LDL-C levels and a smaller transverse diameter of the left atrium increased the risk of PS. The modified RoPE score was derived by assigning 1 point each for high LDL-C levels and the absence of transverse diameter enlargement in the left atrium. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves for the classical and modified RoPE score distinguishing PS were 0.661 and 0.798, respectively.

Conclusion: LDL-C levels and transverse diameter of the left atrium were identified as independent risk factors for PS. The modified RoPE scoring system exhibited superior performance in assessing the risk of PS compared to the original RoPE score.

Background: There has been a protracted effort to identify reliable targets for migraine. It is believed that each year, hundreds of millions of individuals worldwide suffer from migraines, making this widespread neurological ailment the second leading cause of years of disability worldwide. The rationale of this study is to identify the major targets involved in migraine attacks.

Methods: For this review, specialized databases were searched, such as PubMed, EMBASE, DynaMed Plus, and Science Direct databases that included the pathophysiological mechanisms of migraine, focusing on in vitro and in vivo studies in the clinical management of migraine.

Results: Calcitonin gene-related peptide, Pituitary adenylate cyclase-activating polypeptide (PACAP), NOD-like receptor Protein (NLRP3), Serotonin, and some other neuroinflammatory biomarkers are collectively responsible for the cerebral blood vessel dilation and involved in the nociceptive pain which leads to migraine attack.

Conclusion: Migraine biomarkers such as CGRP, PACAP, NLRP3, Nitric oxide synthase, MMP9, and Serotonin could be targets for developing drugs. Present marketed medications temporarily reduce symptoms and pain and have serious cardiovascular side effects. It is suggested that herbal treatment may help prevent migraine attacks without adverse effects. Natural biomolecules that may give better treatment than the present marketed medication and full fledge research should be carried out with natural biomarkers by the Network Pharmacological approach.

Background: Branch atheromatous disease (BAD) and lacunar infract (LI) are the different mechanisms of subtypes of acute stroke. We aimed to investigate perfusion deficits and clinical characteristics of the different mechanisms of two subtypes of acute stroke.

Materials and methods: Five hundred and ninety-nine CTP examinations were retrospectively reviewed between January and December 2021 in patients with acute stroke symptoms with CTP within 12 hours and MRI within 7 days of symptom onset. Based on diffusion MRI, the patients were assigned to one of two subtypes: BAD and LI. Lesion volumes were measured on NCCT, CTA, CBV, CBF, MTT, and TTP maps by region-of-interest analysis and were confirmed by follow-up MRI.

Results: One hundred thirty-three patients met the inclusion criteria (26.3% female). The BAD group was present in 104 of 133 (78.2%), and the LI group 29 of 133 (21.8%). Based on CT perfusion, 42 of 78 (53.8%) BAD group and 5 of 18 (27.8%) LI group had perfusion deficits in the supratentorial region. BAD had a higher proportion of abnormal perfusion than LI patients, with a significant difference (P < 0.05). The sensitivity of CTP ranged from 21.4% (CBV) to 90.5% (TTP); specificity ranged from 97.2% (TTP) to 100% (CBV, CBF, and MTT) in BAD patients.

Conclusion: CTP has high specificity in identifying BAD. Compromised perfusion deficits are more presented in BAD patients compared with LI. CT perfusion imaging may be useful for determining the clinical significance of perfusion abnormalities in BAD occurrence.

Background: A protective and regulatory barrier between the blood and the brain is constituted by the blood-brain barrier (BBB), which comprises microvascular endothelial cells providing homeostatic regulation of the central nervous system (CNS). Inflammation compromises the BBB and contributes to many CNS disorders. Anti-inflammatory effects are exerted by glucocorticoids (GCs) on a variety of cells. These GCs include dexamethasone (Dex), which is used for the treatment of inflammatory diseases and recently for the treatment of COVID-19.

Aim: The purpose of this study was to determine whether low or high concentrations of Dex can attenuate the inflammatory response induced by lipopolysaccharide (LPS) in the in vitro BBB model.

Methods: Brain endothelial cells (bEnd.5) were cultured and exposed to LPS (100ng/ml) and subsequently co-treated with Dex to investigate whether selected concentrations of Dex (0.1, 5, 10, 20μM) can modulate the inflammatory effects of LPS on bEnd.5 cells. Cell viability, cell toxicity, and cell proliferation were investigated, as well as the monitoring of membrane permeability (Trans Endothelial Electrical Resistance-TEER), and Enzyme-Linked Immune Assay (ELISA) kits were used to identify and quantify the presence of inflammatory cytokines (TNF-α and IL-1β).

Results: Dex, at a lower dosage (0.1μM, but not higher doses), was able to attenuate the inflammatory effects of LPS on bEnd.5 cells. Lower doses of Dex (0.1μM) had no detrimental effects on bEnd.5 cells, while higher Dex doses (5-20μM) decreased bEnd.5 viability, increased bEnd.5 cell toxicity, increased bEnd.5 cell monolayer permeability, and increased proinflammatory cytokine secretion.

Conclusion: These results indicate that treatment of brain vascular inflammation with low doses of Dex should be advocated, while higher doses promote vascular inflammation.

Background: Lacunae and white matter hyperintensity (WMH) are two crucial imaging biomarkers of cerebral small vessel disease (CSVD). Multiple studies have revealed a close relationship between WMH and lacunae and found that a double penumbra existed at the edge of WMH that affects lacunae formation. The study aimed to explore the spatial distribution characteristics and possible influencing factors of lacuna in relation to white matter hyperintensity in patients with CSVD.

Methods: A total of 480 CSVD patients with WMH and with or without lacunae were included. Data about blood biochemical indicators, cerebrovascular CT angiography, 24-hour ambulatory blood pressure and ambulatory electrocardiogram, brain magnetic resonance imaging, and transcranial Doppler ultrasound were gathered from all subjects. They were categorised into four groups based on the spatial interaction between lacunae and WMH. Univariate analyses and multiple logistic regression analyses were used to compare the differences in traditional vascular risk factors, heart rate and blood pressure indicators, arterial pulsatility index (PI) values, and arterial stenosis among different groups.

Results: The average age of 480 patients was (58.63 ± 11.91) years, with 347 males (72.3%). Univariate analysis indicated that age, fasting blood glucose, triglycerides, total cholesterol, highdensity lipoprotein, 24-hour and daytime and night systolic and diastolic blood pressure, nocturnal heart rate, heart rate variability, PI values of ipsilateral and contralateral MCA (middle cerebral artery) and ICA (Internal carotid artery) of the lacunae, Fazekas score of PWMH (periventricular white matter hyperintensities), the proportion of MCA or ICA with stenosis rate over 50% on the ipsilateral side of the lacunae were significantly different between different groups (p < 0.05). High fasting blood glucose (OR=1.632, 95% CI= (1.128, 2.361), p =0.009), (OR=1.789, 95%CI= (1.270, 2.520), p = 0.001), (OR=1.806, 95% CI= (1.292, 2.524), p =0.001) was identified as a risk factor for lacunae formation by logistic regression analysis.

Conclusion: High fasting blood glucose can be considered a risk factor for lacunae formation in patients with WMH. The more severe the PWMH and the higher the nocturnal heart rate, the more likely the lacunae, as well as PWMH, overlap completely. Ipsilateral arteriosclerosis and stenosis are independent risk factors for no contact between lacunae and PWMH.

Introduction: The aim is to establish a rat model of infraorbital neuroinflammation with less trauma, stable pain, and a long duration of pain. The pathogenesis of TN is not fully clear. There are various models of TN in rats with different disadvantages, such as damaging the surrounding structures and inaccuracy of location for infraorbital nerve (ION). We aim to establish a rat model of infraorbital neuroinflammation with minimal trauma, a simple operation, and accurate positioning under CT guidance to help us study the pathogenesis of trigeminal neuralgia.

Methods: Thirty-six adult male Sprague Dawley rats (180-220 g) were randomly divided into 2 groups and injected with talc suspension or saline through the infraorbital foramen (IOF) under CT guidance. Mechanical thresholds were measured in the right ION innervation region of 24 rats over 12 postoperative weeks. At 4 weeks, 8 weeks, and 12 weeks after the operation, the inflammatory involvement of the surgical area was evaluated by MRI, and neuropathy was observed using a transmission electron microscope (TEM).

Results: The talc group had a significant decrease in the mechanical threshold at 3 days after surgery that continued until 12 weeks post-operation, and the talc group had a significantly lower mechanical threshold than the saline group 10 weeks post-operation. The talc group had significantly impaired trigeminal nerve (TGN) myelin after 8 weeks post-operation.

Conclusion: The rat model of infraorbital neuroinflammation established by CT-guided injection of talc into the IOF is a simple operation that results in less trauma, stable pain, and a long duration of pain. Moreover, infraorbital neuroinflammation in peripheral branches of the TGN can cause demyelination of the TGN in the intracranial segment.

Purpose: To characterize the macula microvasculature using fractal dimension (FD) in hypertensive white matter hyperintensity (WMH) participants and explore the association between the microvascular changes and serum uric acid levels.

Methods: Thirty-eight WMH participants were dementia and stroke-free, and 37 healthy controls were enrolled. Optical coherence tomographic angiography (OCTA) was used to image the superficial vascular complex (SVC), deep vascular complex (DVC), and inner vascular complex (IVC) in a 2.5-mm diameter concentric circle (excluding the foveal avascular zone FAZ). A commercial algorithm was used to quantify the complexity and density of the three capillary layers by fractal analysis.

Results: WMH participants showed significantly lower FD value in the SVC (P = 0.002), DVC (P < 0.001) and IVC (P = 0.012) macula microvasculature compared with control group. After adjusting for risk factors (hypertension, diabetes, age and gender) SVC (P = 0.035) and IVC (P = 0.030) significantly correlated with serum uric acid.

Conclusion: Serum uric acid levels are associated with microvascular changes in WMH. Fractal dimension based on OCTA imaging could help quantitatively characterize the macula microvasculature changes in WMH and may be a potential screening tool to detect serum uric acid level changes.

Background: Increasing evidence shows that electroacupuncture pretreatment (EP) plays a crucial role in cerebral ischemia-reperfusion (I/R) injury, and cerebral I/R injury is the most serious complication of ischemic stroke treatment. The role of miR-155-5p in cerebral I/R injury has been studied, but the regulation of EP on miR-155-5p has not been reported.

Methods: The middle cerebral artery occlusion (MCAO) mice were used to investigate the role of EP in cerebral I/R injury. Longa and modified neurological severity scores (mNSS) were used to evaluate neurological impairment. HE staining and TUNEL staining were used to evaluate brain injury. The expressions of miR-155-5p, Yin Yang 1 (YY1) and p53 were detected by qRT-PCR. The expressions of related proteins were detected by western blot. The binding of YY1 to miR- 155-5p was verified by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. Mice brain microvascular endothelial cells (BMECs) were isolated and cultured for in vitro experiments. Oxygen-glucose deprivation/reoxygenation (OGD/R) was used to verify the role of YY1, p53 and miR-155-5p in cerebral I/R injury in vitro.

Results: MCAO modeling induced brain injury, apoptosis, and increased levels of miR-155-5p, YY1, and p53. EP markedly alleviated brain injury and reduced levels of miR-155-5p, p53, and YY1. miR-155 agomir markedly increased the expression of miR-155-5p and p53. miR-155 antagomir decreased the levels of miR-155-5p and p53. Dual-luciferase reporter and ChIP assay verified that YY1 regulated miR-155-5p expression. YY1 shNRA greatly decreased miR-155-5p and p53. Inhibition of p53 decreased miR-155-5p expression. Both miR-155-5p inhibitor and YY1 shRNA promoted proliferation, inhibited apoptosis, and decreased levels of ICAM-1 and Eselectin of OGD/R-treated BMECs. Inhibition of p53 strengthened the effect of miR-155-5p inhibitor and YY1 shNRA on BMECs.

Conclusion: Electroacupuncture pretreatment alleviates cerebral ischemia-reperfusion injury by regulating the YY1/p53/miR-155-5p axis.