423 results match your criteria vegf bbb


Systemic infection exacerbates cerebrovascular dysfunction in Alzheimer's disease.

Brain 2021 Mar 16. Epub 2021 Mar 16.

Dementia Research Group, Bristol Medical School, University of Bristol, Bristol, UK.

We studied the effects of systemic infection on brain cytokine level and cerebral vascular function in Alzheimer's disease (AD) and vascular dementia (VaD), in superior temporal cortex (BA22) from AD (n = 75), VaD (n = 22) and age-matched controls (n = 46), stratified according to the presence or absence of terminal systemic infection. Brain cytokine levels were measured using Mesoscale Discovery Multiplex Assays and markers of cerebrovascular function were assessed by ELISA. Multiple brain cytokines were elevated in AD and VaD: Interleukin (IL)-15 and IL-17A were maximally elevated in end-stage Alzheimer's disease (Braak tangle stage V-VI) whereas IL-2, IL-5, IL12p40 and IL-16 were highest in intermediate Braak tangle stage III-IV disease. Read More

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Developmental regulation of barrier- and non-barrier blood vessels in the CNS.

Authors:
A Ben-Zvi S Liebner

J Intern Med 2021 Mar 4. Epub 2021 Mar 4.

Institute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.

The blood-brain barrier (BBB) is essential for creating and maintaining tissue homeostasis in the central nervous system (CNS), which is key for proper neuronal function. In most vertebrates, the BBB is localized to microvascular endothelial cells that acquire barrier properties during angiogenesis of the neuroectoderm. Complex and continuous tight junctions, and the lack of fenestrae combined with low pinocytotic activity render the BBB endothelium a tight barrier for water-soluble molecules that may only enter the CNS via specific transporters. Read More

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Cadmium-induced dysfunction of the blood-brain barrier depends on ROS-mediated inhibition of PTPase activity in zebrafish.

J Hazard Mater 2021 Jan 21;412:125198. Epub 2021 Jan 21.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address:

Increasing evidence has demonstrated that cadmium accumulation in the blood increases the risk of neurological diseases. However, how cadmium breaks through the blood-brain barrier (BBB) and is transferred from the blood circulation into the central nervous system is still unclear. In this study, we examined the toxic effect of cadmium chloride (CdCl) on the development and function of BBB in zebrafish. Read More

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January 2021

Recombinant Human Growth Hormone Activates Neuroprotective Growth Factors in Hypoxic Brain Injury in Neonatal Mice.

Endocrinology 2021 Mar;162(3)

Department of Pediatrics, Division of Neuropediatrics, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.

Perinatal hypoxia severely disrupts cerebral metabolic and maturational programs beyond apoptotic cell death. Antiapoptotic treatments such as erythropoietin are suggested to improve outcomes in hypoxic brain injury; however, the results are controversial. We analyzed the neuroprotective effects of recombinant human growth hormone (rhGH) on regenerative mechanisms in the hypoxic developing mouse brain in comparison to controls. Read More

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Network Pharmacology Reveals the Mechanism of Activity of Tongqiao Huoxue Decoction Extract Against Middle Cerebral Artery Occlusion-Induced Cerebral Ischemia-Reperfusion Injury.

Front Pharmacol 2020 11;11:572624. Epub 2021 Jan 11.

Key Laboratory of Chinese Medicinal Formula of Anhui Province, Anhui University of Chinese Medicine, Hefei, China.

Several clinical therapies such as tissue repair by replacing injured tissues with functional ones have been reported; however, there is great potential for exploring traditional herbal-induced regeneration with good safety. Tongqiao Huoxue Decoction (TQHXD), a well-known classical traditional Chinese medicinal formula, has been widely used for clinical treatment of stroke. However, biological activity and mechanisms of action of its constituents toward conferring protection against cerebral ischemia-reperfusion (I/R) injury remain unclear. Read More

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January 2021

The application of nanoparticles in cancer immunotherapy: Targeting tumor microenvironment.

Bioact Mater 2021 Jul 26;6(7):1973-1987. Epub 2020 Dec 26.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China.

The tumor development and metastasis are closely related to the structure and function of the tumor microenvironment (TME). Recently, TME modulation strategies have attracted much attention in cancer immunotherapy. Despite the preliminary success of immunotherapeutic agents, their therapeutic effects have been restricted by the limited retention time of drugs in TME. Read More

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Mediators of cerebral hypoperfusion and blood-brain barrier leakiness in Alzheimer's disease, vascular dementia and mixed dementia.

Brain Pathol 2021 Jan 7:e12935. Epub 2021 Jan 7.

Dementia Research Group, Institute of Clinical Neurosciences, Bristol Medical School, University of Bristol, Bristol, UK.

In vascular dementia (VaD) and Alzheimer's disease (AD), cerebral hypoperfusion and blood-brain barrier (BBB) leakiness contribute to brain damage. In this study, we have measured biochemical markers and mediators of cerebral hypoperfusion and BBB in the frontal (BA6) and parietal (BA7) cortex and underlying white matter, to investigate the pathophysiology of vascular dysfunction in AD, VaD and mixed dementia. The ratio of myelin-associated glycoprotein to proteolipid protein-1 (MAG:PLP1), a post-mortem biochemical indicator of the adequacy of ante-mortem cerebral perfusion; the concentration of fibrinogen adjusted for haemoglobin level, a marker of blood-brain barrier (BBB) leakiness; the level of vascular endothelial growth factor-A (VEGF), a marker of tissue hypoxia; and endothelin-1 (EDN1), a potent vasoconstrictor, were measured by ELISA in the frontal and parietal cortex and underlying white matter in 94 AD, 20 VaD, 33 mixed dementia cases and 58 age-matched controls. Read More

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January 2021

Vanucizumab mode of action: Serial biomarkers in plasma, tumor, and skin-wound-healing biopsies.

Transl Oncol 2021 Feb 15;14(2):100984. Epub 2020 Dec 15.

Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address:

Vanucizumab is a novel bispecific antibody inhibiting vascular endothelial growth factor (VEGF-A) and angiopoietin-2 (Ang-2) that demonstrated safety and anti-tumor activity in part I of a phase I study of 42 patients with advanced solid tumors. Part II evaluated the pharmacodynamic effects of vanucizumab 30 or 15 mg/kg every 2 weeks in 32 patients. Serial plasma samples, paired tumor, and skin-wound-healing biopsies were taken over 29 days to evaluate angiogenic markers. Read More

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February 2021

Gold nanoparticles carrying or not anti-VEGF antibody do not change glioblastoma multiforme tumor progression in mice.

Heliyon 2020 Nov 25;6(11):e05591. Epub 2020 Nov 25.

Laboratory of Vascular Nanopharmacology, Department of Pharmacology, Institute of Biomedical Sciences I, University of Sao Paulo, Sao Paulo, SP, Brazil.

Aims: Glioblastoma multiforme (GBM) is the most devastating malignant primary brain tumor known. Life expectance is around 15 months after diagnosis. Several events contribute to the GBM progression such as uncontrolled genetic cancer cells proliferation, angiogenesis (mostly vascular endothelial growth factor (VEGF)-mediated), tissue invasion, glioma stem cell activity, immune system failure, and a hypoxic and inflammatory tumor microenvironment. Read More

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November 2020

Coicis semen protects against focal cerebral ischemia-reperfusion injury by inhibiting oxidative stress and promoting angiogenesis via the TGFβ/ALK1/Smad1/5 signaling pathway.

Aging (Albany NY) 2020 11 16;13(1):877-893. Epub 2020 Nov 16.

Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.

Background: Ischemic stroke is a devastating disease that causes long-term disability. However, its pathogenesis is unclear, and treatments for ischemic stroke are limited. Recent studies indicate that oxidative stress is involved in the pathological progression of ischemic stroke and that angiogenesis participates in recovery from ischemic stroke. Read More

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November 2020

Evaluation of PTEN Inhibitor Following Spinal Cord Injury on Recovery of Voiding Efficiency and Motor Function Observed by Regeneration in Spinal Cord.

Int Neurourol J 2020 Nov 23;24(Suppl 2):104-110. Epub 2020 Nov 23.

Department of Urology, Chungnam National University Sejong Hospital, Chungnam National University College of Medicine, Sejong, Korea.

Purpose: Neurogenic bladder (NB) associated with spinal cord injury (SCI) is a serious health problem. However, no effective treatment has been developed for SCI patients with NB. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitors have been proposed as a promising option for inducing neural regeneration. Read More

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November 2020

circ_2858 Helps Blood-Brain Barrier Disruption by Increasing VEGFA via Sponging miR-93-5p during Meningitis.

Mol Ther Nucleic Acids 2020 Dec 4;22:708-721. Epub 2020 Oct 4.

The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Meningitic invasion of the host brain can lead to increased blood-brain barrier (BBB) permeability. Circular RNAs (circRNAs) are non-coding RNAs, highly abundant in the brain, that are widely involved in the pathological processes of central nervous system (CNS) disorders; however, whether circRNAs participate in the regulation of BBB permeability during meningitis remains unknown. Here, we identified a novel circRNA, circ_2858, that was significantly upregulated in human brain microvascular endothelial cells (hBMECs) upon meningitic infection. Read More

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December 2020

Theta-burst transcranial magnetic stimulation promotes stroke recovery by vascular protection and neovascularization.

Theranostics 2020 26;10(26):12090-12110. Epub 2020 Oct 26.

Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912, USA.

The integrity and function of the blood-brain barrier (BBB) is compromised after stroke. The current study was performed to examine potential beneficial effects and underlying mechanisms of repetitive transcranial magnetic stimulation (rTMS) on angiogenesis and vascular protection, function, and repair following stroke, which are largely unknown. Using a rat photothrombotic (PT) stroke model, continuous theta-burst rTMS was administered once daily to the infarcted hemisphere for 5 min, beginning 3 h after PT stroke. Read More

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October 2020

Establishment of an experimental rat model of high altitude cerebral edema by hypobaric hypoxia combined with temperature fluctuation.

Brain Res Bull 2020 12 24;165:253-262. Epub 2020 Oct 24.

Department of Pharmacy, The 940th Hospital of Joint Logistics Support Force, Lanzhou, Gansu, 730050, People's Republic of China. Electronic address:

High altitude cerebral edema (HACE) is a kind of life threat disease encountered at high altitude, but the precise pathogenesis of it is far more understood. Hypobaic hypoxia (HH) and cold are conditions characteristic of high altitude environment. HH is always considered as the central causative factor for the development of HACE, but the effect of cold stress on HACE has been rarely investigated. Read More

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December 2020

Effects of salvianolate lyophilized injection combined with Xueshuantong injection in regulation of BBB function in a co-culture model of endothelial cells and pericytes.

Brain Res 2021 Jan 28;1751:147185. Epub 2020 Oct 28.

Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address:

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. The salvianolate lyophilized injection (SLI) and Xueshuantong Injection (XST) are two standardized Chinese medicine injections which have been widely used in the treatment of cerebrovascular diseases. Salvianolic acid B (Sal B) and Notoginsenoside R1 (NR1) is respectively one of the active constituents of SLI and XST, which have certain effects on stroke. Read More

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January 2021

Spatiotemporal variations of vascular endothelial growth factor in the brain of diabetic cognitive impairment.

Pharmacol Res 2021 Jan 11;163:105234. Epub 2020 Oct 11.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address:

Although it is feared that diabetes-induced cognitive impairment (DCI) will become a major clinical problem worldwide in the future, its detailed pathological mechanism is not well known. Because patients with diabetes have various complications of vascular disease, vascular disorders in the brain are considered to be one of the main mechanisms of DCI. Mounting evidence suggests that the vascular endothelial growth factor (VEGF) family plays a crucial role in the development of DCI. Read More

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January 2021

Atorvastatin disrupts primary human brain microvascular endothelial cell functions via prenylation-dependent mitochondrial inhibition and oxidative stress.

Fundam Clin Pharmacol 2021 Apr 27;35(2):341-350. Epub 2020 Oct 27.

Department of Neurology, Hubei Hospital of Integrated Traditional Chinese and Western Medicine, Wuhan, China.

Primary human brain microvascular endothelial cell (HBMEC) is the major component of the blood-brain barrier (BBB). Atorvastatin, a HMG-CoA reductase inhibitor, is a cholesterol-lowering drug commonly used to reduce the risk for cardiovascular disease. Numerous studies have reported the pleiotropic effects of atorvastatin on endothelial cells, but the findings are controversial and inconclusive. Read More

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The three-phase enriched environment paradigm promotes neurovascular restorative and prevents learning impairment after ischemic stroke in rats.

Neurobiol Dis 2020 12 23;146:105091. Epub 2020 Sep 23.

School of Traditional Chinese Medicine, Capital Medical University, Beijing, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing, China. Electronic address:

Enriched environment (EE) with a complex combination of sensorimotor, cognitive and social stimulations has been shown to enhance brain plasticity and improve recovery of functions in animal models of stroke. The present study extended these findings by assessing whether the three-phase EE intervention paradigm would improve neurovascular remodeling following ischemic stroke. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). Read More

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December 2020

Oxytocin Reduces Brain Injury and Maintains Blood-Brain Barrier Integrity After Ischemic Stroke in Mice.

Neuromolecular Med 2020 12 11;22(4):557-571. Epub 2020 Sep 11.

Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran.

The present study was designed to determine the effect of different doses of oxytocin (OXT) on neuronal injury, spatial memory, blood-brain barrier (BBB) integrity and to explore possible underlying molecular mechanisms in the early stage of stroke in mice. Stroke model was generated by middle cerebral artery occlusion (MCAO) for 60 min and 24 h reperfusion in mice. OXT at doses of 1, 2, 4 and 8 IU/per mouse was administrated intranasally at the beginning of brain ischemia. Read More

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December 2020

The Protective Effects of Juglanin in Cerebral Ischemia Reduce Blood-Brain Barrier Permeability via Inhibition of VEGF/VEGFR2 Signaling.

Drug Des Devel Ther 2020 5;14:3165-3175. Epub 2020 Aug 5.

Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, People's Republic of China.

Introduction: Ischemic brain injury due to stroke or other pathologies is a major contributor to disability and mortality worldwide. Upon the occurrence of stroke, neuronal cells undergo apoptosis due to the deprivation of oxygen and nutrients and failure of the blood-brain barrier (BBB). In the moments immediately following a stroke, widespread perfusion resulting from hyperpermeability is accompanied by an acute inflammatory response, which induces neovascularization and often permanent neurological injury. Read More

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Expression of VEGF- and tight junction-related proteins in the neocortical microvasculature of patients with drug-resistant temporal lobe epilepsy.

Microvasc Res 2020 11 13;132:104059. Epub 2020 Aug 13.

Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav) Sede Sur, Ciudad de México, Mexico.

The blood-brain barrier (BBB) maintains the optimal microenvironment for brain function. Tight junctions (TJs) allow endothelial cells to adhere to each other, leading to the formation of a barrier that prevents the penetration of most molecules via transcellular routes. Evidence has indicated that seizure-induced vascular endothelial growth factor (VEGF) type 2 receptor (VEGFR-2) pathway activation weakens TJs, inducing vasodilatation and increasing vascular permeability and subsequent brain injury. Read More

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November 2020

Inducers of the endothelial cell barrier identified through chemogenomic screening in genome-edited hPSC-endothelial cells.

Proc Natl Acad Sci U S A 2020 08 5;117(33):19854-19865. Epub 2020 Aug 5.

Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215;

The blood-retina barrier and blood-brain barrier (BRB/BBB) are selective and semipermeable and are critical for supporting and protecting central nervous system (CNS)-resident cells. Endothelial cells (ECs) within the BRB/BBB are tightly coupled, express high levels of Claudin-5 (CLDN5), a junctional protein that stabilizes ECs, and are important for proper neuronal function. To identify novel CLDN5 regulators (and ultimately EC stabilizers), we generated a CLDN5-P2A-GFP stable cell line from human pluripotent stem cells (hPSCs), directed their differentiation to ECs (CLDN5-GFP hPSC-ECs), and performed flow cytometry-based chemogenomic library screening to measure GFP expression as a surrogate reporter of barrier integrity. Read More

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Reciprocal Interplay Between Astrocytes and CD4+ Cells Affects Blood-Brain Barrier and Neuronal Function in Response to β Amyloid.

Front Mol Neurosci 2020 3;13:120. Epub 2020 Jul 3.

Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.

: In Alzheimer's disease (AD) neuronal degeneration is associated with gliosis and infiltration of peripheral blood mononuclear cells (PBMCs), which participate in neuroinflammation. Defects at the blood-brain barrier (BBB) facilitate PBMCs migration towards the central nervous system (CNS) and in particular CD4+ T cells have been found in areas severely affected in AD. However, the role of T cells, once they migrate into the CNS, is not well defined. Read More

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Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis.

Microvasc Res 2020 11 14;132:104042. Epub 2020 Jul 14.

Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States of America; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States of America; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, United States of America. Electronic address:

During brain development, chemical cues released by developing neurons, cellular signaling with pericytes, and mechanical cues within the brain extracellular matrix (ECM) promote angiogenesis of brain microvascular endothelial cells (BMECs). Angiogenesis is also associated with diseases of the brain due to pathological chemical, cellular, and mechanical signaling. Existing in vitro and in vivo models of brain angiogenesis have key limitations. Read More

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November 2020

VEGF/VEGFR-2 system exerts neuroprotection against Phoneutria nigriventer spider envenomation through PI3K-AKT-dependent pathway.

Toxicon 2020 Oct 7;185:76-90. Epub 2020 Jul 7.

Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil; Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. Electronic address:

This study was undertaken to elucidate why VEGF/VEGFR-2 is elevated in the hippocampus of rats injected with Phoneutria nigriventer spider venom (PNV). PNV delays Na channels inactivation; blocks Ca and K channels, increases glutamate release, causes blood-brain breakdown (BBBb), brain edema and severe excitotoxicity. Analytical FT-IR spectroscopy showed profound alteration in molecular biochemical state, with evidences for VEGFR-2 (KDR/Flk-1) signaling mediation. Read More

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October 2020

Endothelin receptor antagonists alleviate blood-brain barrier disruption and cerebral edema in a mouse model of traumatic brain injury: A comparison between bosentan and ambrisentan.

Neuropharmacology 2020 09 16;175:108182. Epub 2020 Jun 16.

Laboratory of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyama-Kita Higashinada, Kobe, 668-8558, Japan. Electronic address:

Traumatic brain injury (TBI) is induced by the immediate physical disruption of brain tissue. TBI causes disruption of the blood-brain barrier (BBB) and brain edema. In the cerebrospinal fluid (CSF) of TBI patients, endothelin-1 (ET-1) is increased, suggesting that ET-1 aggravates TBI-induced brain damage. Read More

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September 2020

Hypertonic saline mediates the NLRP3/IL-1β signaling axis in microglia to alleviate ischemic blood-brain barrier permeability by downregulating astrocyte-derived VEGF in rats.

CNS Neurosci Ther 2020 Jun 12. Epub 2020 Jun 12.

Department of Critical Care Medicine, The First Affiliated Hospital, University of South China, Hengyang, China.

Introduction: The aim of this study was to explore whether the antibrain edema of hypertonic saline (HS) is associated with alleviating ischemic blood-brain barrier (BBB) permeability by downregulating astrocyte-derived vascular endothelial growth factor (VEGF), which is mediated by microglia-derived NOD-like receptor protein 3 (NLRP3) inflammasome.

Methods: The infarct volume and BBB permeability were detected. The protein expression level of VEGF in astrocytes in a transient focal brain ischemia model of rats was evaluated after 10% HS treatment. Read More

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HIF-1α is involved in blood-brain barrier dysfunction and paracellular migration of bacteria in pneumococcal meningitis.

Acta Neuropathol 2020 08 11;140(2):183-208. Epub 2020 Jun 11.

Institute for Medical Microbiology and Infection Control, Goethe University, Frankfurt am Main, Germany.

Bacterial meningitis is a deadly disease most commonly caused by Streptococcus pneumoniae, leading to severe neurological sequelae including cerebral edema, seizures, stroke, and mortality when untreated. Meningitis is initiated by the transfer of S. pneumoniae from blood to the brain across the blood-cerebrospinal fluid barrier or the blood-brain barrier (BBB). Read More

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Sirt3 Protects Against Ischemic Stroke Injury by Regulating HIF-1α/VEGF Signaling and Blood-Brain Barrier Integrity.

Cell Mol Neurobiol 2020 Jun 4. Epub 2020 Jun 4.

School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.

Sirtuin 3 (Sirt3) is a member of the Sirtuin family proteins and known to regulate multiple physiological processes such as metabolism and aging. As stroke is an aging-related disease, in this work, we attempt to examine the role and potential mechanism of Sirt3 in regulating ischemic stroke by using a permanent middle cerebral artery occlusion (pMCAO) model in wild type (WT) and Sirt3 knockout (KO) mice, coupled with oxygen glucose deprivation (OGD) experiments in cultured primary astrocytes. Sirt3 deficiency aggravated neuronal cell apoptosis and neurological deficits after brain ischemia. Read More

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VEGI Improves Outcomes in the Early Phase of Experimental Traumatic Brain Injury.

Neuroscience 2020 07 5;438:60-69. Epub 2020 May 5.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Neurological Institute, Tianjin, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China. Electronic address:

Excessive expression of vascular endothelial growth factor (VEGF) is a common cause of blood-brain barrier (BBB) breakdown that triggers severe complications following traumatic brain injury (TBI). It has been shown that inhibition of VEGF activities may attenuate cerebral edema in pathological conditions. Vascular endothelial growth inhibitor (VEGI; also known as TNFSF15), a cytokine produced largely by vascular endothelial cells, is capable of downregulating VEGF expression and inhibiting VEGF receptor-2 (VEGFR2) activation. Read More

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