Ischemic Stroke and Cerebral Microbleeds: A Two-Sample Bidirectional Mendelian Randomization Study.

INTRODUCTION: Recent observational studies have reported the association between ischemic stroke (IS) and cerebral microbleeds (CMBs). Whether this reflects a causal association remains to be established. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) analysis to comprehensively evaluate the causal association of IS and CMBs. METHODS: The summary-level genome-wide association studies (GWASs) data of IS were obtained from the GIGASTROKE consortium (62,100 European ancestry cases and 1,234,808 European ancestry controls). All IS cases could be further divided into large-vessel atherosclerosis stroke (LVS, n = 6399), cardio-embolic stroke (CES, n = 10,804) and small-vessel occlusion stroke (SVS, n = 6811). Meanwhile, we used publicly available summary statistics from published GWASs of CMBs (3556 of the 25,862 European participants across 2 large initiatives). A bidirectional MR analysis was conducted using inverse-variance weighting (IVW) as the major outcome, whereas MR-Egger and weighted median (WM) were used to complement the IVW estimates as they can provide more robust estimates in a broader set of scenarios but are less efficient (wider CIs). A Bonferroni-corrected threshold of p < 0.0125 was considered significant, and p values between 0.0125 and 0.05 were considered suggestive of evidence for a potential association. RESULTS: We detected that higher risk of IS [IVW odds ratio (OR) 1.47, 95% confidence interval (CI) 1.04-2.07, p = 0.03] and SVS (IVW OR 1.62, 95% CI 1.07-2.47, p = 0.02) were significantly associated with CMBs. Reverse MR analyses found no significant evidence for a causal effect of CMBs on IS and its subtypes. CONCLUSIONS: Our study provides potential evidence that IS and SVS are causally linked to increased risk of CMBs. Further research is needed to determine the mechanisms of association between IS and CMBs.

A review on surgical treatment options in gliomas.

Gliomas are one of the most common primary central nervous system tumors, and surgical treatment remains the principal role in the management of any grade of gliomas. In this study, based on the introduction of gliomas, we review the novel surgical techniques and technologies in support of the extent of resection to achieve long-term disease control and summarize the findings on how to keep the balance between cytoreduction and neurological morbidity from a list of literature searched. With modern neurosurgical techniques, gliomas resection can be safely performed with low morbidity and extraordinary long-term functional outcomes.

Polyoxometalate@MOF derived porous carbon-supported MoO2/MoS2 octahedra boosting high-rate lithium storage.

Structural stability and rapid charge-discharge capability of electrode materials are required for high performance lithium-ion batteries (LIBs). The materials derived from polyoxometalates (POMs) show special advantages in inhibiting capacity attenuation, and good dispersion or combination of POMs with metal-organic frameworks (MOFs) is an important method to obtain high activity anode composites for LIBs. In this study, a uniform MoO2/MoS2 heterostructure with surface supported carbon (C-MoO2/MoS2) was successfully fabricated from a [Cu2(BTC)4/3(H2O)2]6[H3PMo12O40] precursor, which showed not only the designed octahedral morphology but also fast charge transfer, long working life, and high rate performance. Superior reversible lithium storage capacity of 1047 mA h g-1 after 300 cycles was obtained at 1 A g-1. Even after 700 cycles at 5 A g-1, the discharge specific capacity of 646 mA h g-1 was maintained, and rate capability of 610 mA h g-1 could be achieved at 10 A g-1. The high capacitive contribution could be explained by the relatively large specific surface area of porous C-MoO2/MoS2, which was mainly caused by the supported carbon network and MoS2 nanosheets, resulting in fast lithiation/delithiation processes.

Treatments of unruptured brain arteriovenous malformations: A systematic review and meta-analysis.

BACKGROUND: The best therapeutic option for unruptured brain arteriovenous malformations (bAVMs) patients is disputed. OBJECTIVE: To assess the occurrence of obliteration and complications of patients with unruptured bAVMs after various treatments. METHODS: A systematic literature search was performed in PubMed, EMBASE, Web of Science, and so on to identify studies fulfilling predefined inclusion criteria. Baseline, treatment, and outcomes data were extracted for statistical analysis. RESULTS: We identified 28 eligible studies totaling 5852 patients. The obliteration rates were 98% in microsurgery group (95% confidence interval (CI): 96%-99%, I2 = 74.5%), 97% in surgery group (95%CI: 95%-99%, I2 = 18.3%), 87% in endovascular treatment group (95%CI: 80%-93%, I2 = 0.0%), and 68% in radiosurgery group (95%CI: 66%-69%, I2 = 92.0%). The stroke or death rates were 1% in microsurgery group (95%CI: 0%-2%, I2 = 0.0%), 0% in surgery group (95%CI: 0%-1%, I2 = 0.0%), 4% in endovascular treatment group (95%CI: 0%-8%, I2 = 85.8%), and 3% in radiosurgery group (95%CI: 3%-4%, I2 = 82.9%). In addition, the proportions of hemorrhage were 2% in microsurgery group (95%CI: 1%-4%, I2 = 0.0%), 23% in endovascular treatment group (95%CI: 7%-39%), and 12% in radiosurgery group (95%CI: 12%-13%, I2 = 99.2%). As to neurological deficit, the occurrence was 9% in microsurgery group (95%CI: 6%-11%, I2 = 94.1%), 20% in surgery group (95%CI: 13%-27%, I2 = 0.0%), 14% in endovascular treatment group (95%CI: 10%-18%, I2 = 64.0%), and 8% in radiosurgery group (95%CI: 7%-9%, I2 = 66.6%). CONCLUSIONS: We found that microsurgery might provide lasting clinical benefits in some unruptured bAVMs patients for its high obliteration rates and low hemorrhage. These findings are helpful to provide a reference basis for neurosurgeons to choose the treatment of patients with unruptured bAVMs.

Appearance of cerebellar cyst following microvascular decompression to treat hemifacial spasm: a report of two cases and literature review.

Microvascular decompression (MVD) is an effective and safe approach for treating hemifacial spasm (HFS). Postoperative complications may include facial nerve palsy, hearing loss, intracerebral haematoma, and brainstem infarction. The occurrence of intracranial cyst following MVD is extremely rare, with few cases documented in the literature. Herein, the cases of two patients with HFS who developed ipsilateral cerebellar cyst following MVD are reported. The first patient was a 50-year-old male presenting with a 6-year history of HFS on the right side of his face. MVD was performed, and 12 days postoperatively he developed dizziness and nausea. Magnetic resonance imaging (MRI) showed a cyst in the ipsilateral cerebellum. Antibiotic treatment provided no benefit, and the cyst was drained. The second patient was a 44-year-old female presenting with a 4-year history of HFS on the right side of her face. MVD was performed, and 18 days following surgery, she developed dizziness and nausea. MRI showed an ipsilateral cerebellar cyst. Conservative treatment was applied and the cyst shrunk. At the 2-month follow-up appointment, symptoms were completely resolved in both patients. Cerebellar cyst is a rare complication following MVD. Timely diagnosis and appropriate treatment should be emphasized, and surgical treatment may be unnecessary.

Weighted gene co-expression network analysis identified six hub genes associated with rupture of intracranial aneurysms.

Intracranial aneurysms (IAs) are characterized by localized dilation or ballooning of a cerebral artery. When IAs rupture, blood leaks into the space around the brain to create a subarachnoid hemorrhage. The latter is associated with a higher risk of disability and mortality. The aims of this study were to gain greater insight into the pathogenesis of ruptured IAs, and to clarify whether identified hub genes represent potential biological markers for assessing the likelihood of IA progression and rupture. Briefly, the GSE36791 and GSE73378 datasets from the National Center of Biotechnology Information Gene Expression Omnibus database were reanalyzed and subjected to a weighted gene co-expression network analysis to test the association between gene sets and clinical features. The clinical significance of these genes as potential biomarkers was also examined, with their expression validated by quantitative real-time PCR. A total of 14 co-expression modules and 238 hub genes were identified. In particular, three modules (labeled turquoise, blue, and brown) were found to highly correlate with IA rupture events. Additionally, six potential biomarkers were identified (BASP1, CEBPB, ECHDC2, GZMK, KLHL3, and SLC2A3), which are strongly associated with the progression and rupture of IAs. Taken together, these findings provide novel insights into potential molecular mechanisms responsible for IAs and they highlight the potential for these particular genes to serve as biomarkers for monitoring IA rupture.

BubR1 Insufficiency Impairs Affective Behavior and Memory Function in Mice.

PURPOSE: Although aging causes functional declines in cognition, the molecular mechanism underlying these declines remains largely unknown. Recently, the spindle checkpoint kinase budding uninhibited by benzimidazole-related 1 (BubR1) has emerged as a key determinant for age-related pathology in various tissues including brain. However, the neurobehavioral impact of BubR1 has not been explored. In this study, we investigated the role of BubR1 in behavioral function. METHODS: To investigate the neurobiological functions of BubR1 in vivo, we utilized transgenic mice harboring BubR1 hypomorphic alleles (BubR1H/H mice), which produce low amounts of BubR1 protein, as well as mice that have specific knockdown of BubR1 in the adult dentate gyrus. To assess anxiety-like behavior, the above groups were subjected to the elevated plus maze and the light-dark test, in addition to utilizing the tail-suspension and forced-swim test to determine depression-like behavior. We used novel object recognition to test for memory-related function. RESULTS: We found that BubR1H/H mice display several behavioral deficits when compared to wild-type littermates, including increased anxiety in the elevated-plus maze test, depression-like behavior in the tail suspension test, as well as impaired memory function in the novel object recognition test. Similar to BubR1H/H mice, knockdown of BubR1 within the adult dentate gyrus led to increased anxiety-like behavior as well as depression-like behavior, and impaired memory function. CONCLUSION: Our study demonstrates a requirement of BubR1 in maintaining proper affective and memory-related behavioral function. These results suggest that a decline in BubR1 levels with advanced age may be a crucial contributor to age-related hippocampal dysfunction.

MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage.

BACKGROUND/AIMS: Acute cerebral ischemia is a manifestation of cerebral vascular insufficiency and has a high mortality. However, the therapy for acute cerebral ischemia is still limited. This study aimed to investigate the effect of microRNA-381 (miR-381) on the repair of nerve injury in rats with acute cerebral ischemia after cerebral lymphatic blockage (CLB) by targeting leucine-rich repeat C4 protein (LRRC4) through the Stromal cell-derived factor-1/CXC chemokine receptor-4 signaling pathway. METHODS: Rat models of CLB and middle cerebral artery occlusion (MCAO) were established, and 56 Wistar rats were divided into sham, MCAO, CLB + MCAO, CLB + MCAO + miR-381 inhibitor, CLB + MCAO + miR-381 mimic, CLB + MCAO + AMD3100 and CLB + MCAO + miR-381 mimic + AMD3100 groups. Modified neurological severity score (mNSS was used to determine nerve injury, TTC staining to measure infarction volume, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry to evaluate cell apoptosis, immunofluorescence to measure BrdU-positive cell number, enzyme-linked immunosorbent assay (ELISA) to determine contents of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), nerve growth factor (NGF) and neurite outgrowth inhibitor -A (Nogo-A), Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting to evaluate expression of miR-381, LRRC4, SDF-1, CXCR4, pERK, Slit2 and vascular endothelial growth factor (VEGF). RESULTS: LRRC4 was a target gene of miR-381. Compared with the results in the CLB + MCAO group, mNSS, infarction volume, apoptosis rate and TNF-α, IL-1ß, IL-6 and Nogo-A contents as well as LRRC4 expression in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups were increased (those in the CLB + MCAO + AMD3100 group > those in the CLB + MCAO + miR-381 mimic + AMD3100 group), while BrdU-positive cell number, contents of NGF and IL-10, and expression of SDF-1, CXCR4, pERK, Slit2 and VEGF in brain tissues were decreased (those in the CLB + MCAO + AMD3100 group < those in the CLB + MCAO + miR-381 mimic + AMD3100 group). The results in the CLB + MCAO + mimic group were opposite of those in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups. CONCLUSION: Taken together, we concluded that up-regulation of miR-381 promoted nerve injury repair in acute cerebral ischemia rats after CLB by negatively regulating LRRC4 through activating the SDF-1/CXCR4 signaling pathway.

6-Hydroxydopamine induces brain vascular endothelial inflammation.

Disruption of the blood-brain barrier associated with endothelial dysfunction is an important hallmark of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a synthetic dopamine derivate often used to model PD as it results in retrograde degeneration of striatal dopaminergic (DA) terminals. Presently, the effects of 6-OHDA on endothelial dysfunction remain unknown. Using a 6-OHDA rodent model of PD, we found that administration of 6-OHDA could increase the expression of endothelial adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin. An in vitro study displayed that treatment with 6-OHDA increased the release of these molecules in human brain microvascular endothelial cells in a dose-dependent manner. Correspondingly, 6-OHDA significantly increased attachment of THP-1 monocytes to brain endothelial cells. In addition, real-time polymerase chain reaction and enzyme-linked immunosorbent assay results indicated that 6-OHDA elevated the production of proinflammatory cytokines, such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Furthermore, 6-OHDA treatment increased the expression of cyclooxygenase-2 and inducible nitric oxide synthase, as well as the production of prostaglandin E2 and nitric oxide. Importantly, 6-OHDA elevated the transcriptional activity of NF-кB by increasing the phosphorylation, degradation, and subsequent nuclear translocation of p65. Mechanistically, the angiotensin II type 1 receptor was found to mediate 6-OHDA-induced endothelial dysfunction. Our findings suggest that 6-OHDA-induced endothelial inflammation may play an important role in the pathogenesis of PD. © 2017 IUBMB Life, 69(11):887-895, 2017.

DISC1 in Astrocytes Influences Adult Neurogenesis and Hippocampus-Dependent Behaviors in Mice.

The functional role of genetic variants in glia in the pathogenesis of psychiatric disorders remains poorly studied. Disrupted-In-Schizophrenia 1 (DISC1), a genetic risk factor implicated in major mental disorders, has been implicated in regulation of astrocyte functions. As both astrocytes and DISC1 influence adult neurogenesis in the dentate gyrus (DG) of the hippocampus, we hypothesized that selective expression of dominant-negative C-terminus-truncated human DISC1 (mutant DISC1) in astrocytes would affect adult hippocampal neurogenesis and hippocampus-dependent behaviors. A series of behavioral tests were performed in mice with or without expression of mutant DISC1 in astrocytes during late postnatal development. In conjunction with behavioral tests, we evaluated adult neurogenesis, including neural progenitor proliferation and dendrite development of newborn neurons in the DG. The ameliorative effects of D-serine on mutant DISC1-associated behaviors and abnormal adult neurogenesis were also examined. Expression of mutant DISC1 in astrocytes decreased neural progenitor proliferation and dendrite growth of newborn neurons, and produced elevated anxiety, attenuated social behaviors, and impaired hippocampus-dependent learning and memory. Chronic treatment with D-serine ameliorated the behavioral alterations and rescued abnormal adult neurogenesis in mutant DISC1 mice. Our findings suggest that psychiatric genetic risk factors expressed in astrocytes could affect adult hippocampal neurogenesis and contribute to aspects of psychiatric disease through abnormal production of D-serine.

Age-related decline in BubR1 impairs adult hippocampal neurogenesis.

Aging causes significant declines in adult hippocampal neurogenesis and leads to cognitive disability. Emerging evidence demonstrates that decline in the mitotic checkpoint kinase BubR1 level occurs with natural aging and induces progeroid features in both mice and children with mosaic variegated aneuploidy syndrome. Whether BubR1 contributes to age-related deficits in hippocampal neurogenesis is yet to be determined. Here we report that BubR1 expression is significantly reduced with natural aging in the mouse brain. Using established progeroid mice expressing low amounts of BubR1, we demonstrate these mice exhibit deficits in neural progenitor proliferation and maturation, leading to reduction in new neuron production. Collectively, our identification of BubR1 as a new and critical factor controlling sequential steps across neurogenesis raises the possibility that BubR1 may be a key mediator regulating aging-related hippocampal pathology. Targeting BubR1 may represent a novel therapeutic strategy for age-related cognitive deficits.

Research Progress of Moyamoya Disease in Children.

During the onset of Moyamoya disease (MMD), progressive occlusion occurs at the end of the intracranial internal carotid artery, and compensatory net-like abnormal vessels develop in the skull base, generating the corresponding clinical symptoms. MMD can affect both children and adults, but MMD in pediatric patients exhibits distinct clinical features, and the treatment prognoses are different from adult patients. Children are the group at highest risk for MMD. In children, the disease mainly manifests as ischemia, while bleeding is the primary symptom in adults. The pathogenesis of MMD in children is still unknown, and some factors are distinct from those in adults. MMD in children could result in progressive, irreversible nerve functional impairment, and an earlier the onset corresponds to a worse prognosis. Therefore, active treatment at an early stage is highly recommended. The treatment methods for MMD in children mainly include indirect and direct surgeries. Indirect surgeries mainly include multiple burr-hole surgery (MBHS), encephalomyosynangiosis (EMS), and encephaloduroarteriosynangiosis (EDAS); direct surgeries mainly include intra- and extracranial vascular reconstructions that primarily consist of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. Indirect surgery, as a treatment for MMD in children, has shown a certain level of efficacy. However, a standard treatment approach should combine both indirect and direct procedures. Compared to MMD in adults, the treatment and prognosis of MMD in children has higher clinical significance. If the treatment is adequate, a satisfactory outcome is often achieved.

An approach for phosphate removal with quartz sand, ceramsite, blast furnace slag and steel slag as seed crystal.

The phosphate removal abilities and crystallization performance of quartz sand, ceramsite, blast furnace slag and steel slag were investigated. The residual phosphate concentrations in the reaction solutions were not changed by addition of the ceramsite, quartz sand and blast furnace slag. The steel slag could provide alkalinity and Ca(2+) to the reaction solution due to its hydration activity, and performed a better phosphate removal performance than the other three. Under the conditions of Ca/P 2.0, pH 8.5 and 10 mg P/L, the phosphate crystallization occurred during 12 h. The quartz sand and ceramsite did not improve the phosphate crystallization, but steel slag was an effective seed crystal. The phosphate concentration decreased drastically after 12 h after addition of steel slag, and near complete removal was achieved after 48 h. The XRD analysis showed that the main crystallization products were hydroxyapatite (HAP) and the crystallinity increased with the reaction time. Phosphate was successfully recovered from low phosphate concentration wastewater using steel slag as seed material.