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https://www.readbyqxmd.com/read/28441414/regional-early-and-progressive-loss-of-brain-pericytes-but-not-vascular-smooth-muscle-cells-in-adult-mice-with-disrupted-platelet-derived-growth-factor-receptor-%C3%AE-signaling
#1
Angeliki Maria Nikolakopoulou, Zhen Zhao, Axel Montagne, Berislav V Zlokovic
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain...
2017: PloS One
https://www.readbyqxmd.com/read/28440874/role-of-glycogen-synthase-kinase-3-in-ischemia-induced-blood-brain-barrier-disruption-in-aged-female-rats
#2
Han Xiao, Mingyang Deng, Binbin Yang, Jianguang Tang, Zhiping Hu
Estrogen receptors have protective effects against ischemic brain injury. However, the molecular mechanisms underlying this phenomenon have yet to be well studied. Given that inhibition of glycogen synthase kinase (GSK3) can reduce cerebral ischemia/reperfusion injury, we hypothesized that estrogen receptors-mediated protective effects against ischemia-induced blood brain barrier (BBB) disruption involve inhibition of GSK3. Thus, we evaluated GSK3 expression in the brain of ovariectomized female rats, and examined the effects of intracerebroventricular pre-treatments of SB216763, GSK3 inhibitor, on BBB permeability following middle cerebral artery occlusion (MCAO)...
April 25, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28435263/neuroprotection-against-apoptosis-of-sk-n-mc-cells-using-rmp-7-and-lactoferrin-grafted-liposomes-carrying-quercetin
#3
Yung-Chih Kuo, Chien-Wei Tsao
A drug delivery system of quercetin (QU)-encapsulated liposomes (LS) grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf) was developed to permeate the blood-brain barrier (BBB) and rescue degenerated neurons, acting as an Alzheimer's disease (AD) pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse human brain microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ) fibrils...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28434009/hypoxic-ischaemic-encephalopathy-and-the-blood-brain-barrier-in-neonates
#4
Wei Ling Amelia Lee, Adina T Michael-Titus, Divyen K Shah
This review aims to highlight a possible relationship between hypoxic-ischaemic encephalopathy (HIE) and the disruption of the blood-brain barrier (BBB). Inflammatory reactions perpetuate a large proportion of cerebral injury. The extent of injury noted in HIE is not only determined by the biochemical cascades that trigger the apoptosis-necrosis continuum of cell death in the brain parenchyma, but also by the breaching of the BBB by pro-inflammatory factors. We examine the changes that contribute to the breakdown of the BBB that occur during HIE at a macroscopic, cellular, and molecular level...
April 22, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28433650/long-noncoding-rna-malat1-is-a-potent-autophagy-inducer-protecting-brain-microvascular-endothelial-cells-against-oxygen-glucose-deprivation-reoxygenation-induced-injure-by-sponing-mir-26b-and-upregulating-ulk2-expression
#5
Zhijun Li, Jing Li, Na Tang
Brain microvascular endothelial cell (BMEC) injury induced by ischemia-reperfusion (I/R) is the initial stage of blood-brain barrier (BBB) disruption, which results in a poor prognosis in ischemic stroke patients. Autophagy has been shown to have protective effects on BMECs against cerebral ischemic insults. However, molecular mechanism of BMEC autophagy during I/R is unclear. Long noncoding RNAs (lncRNAs) are emerging as new factors involved in cell autophagy. LncRNA Malat1 is one of the most highly upregulated I/R or OGD/R-responsive endothelial lncRNA and plays a protective role in BMECs against cerebral ischemic insults...
April 19, 2017: Neuroscience
https://www.readbyqxmd.com/read/28432926/tick-borne-encephalitis-virus-infects-human-brain-microvascular-endothelial-cells-without-compromising-blood-brain-barrier-integrity
#6
Martin Palus, Marie Vancova, Jana Sirmarova, Jana Elsterova, Jan Perner, Daniel Ruzek
Alteration of the blood-brain barrier (BBB) is a hallmark of tick-borne encephalitis (TBE), a life-threating human viral neuroinfection. However, the mechanism of BBB breakdown during TBE, as well as TBE virus (TBEV) entry into the brain is unclear. Here, primary human microvascular endothelial cells (HBMECs) were infected with TBEV to study interactions with the BBB. Although the number of infected cells was relatively low in culture (<5%), the infection was persistent with high TBEV yields (>10(6)pfu/ml)...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28432486/cholesterol-as-a-modifying-agent-of-the-neurovascular-unit-structure-and-function-under-physiological-and-pathological-conditions
#7
REVIEW
Ewelina Czuba, Aleksandra Steliga, Grażyna Lietzau, Przemysław Kowiański
The brain, demanding constant level of cholesterol, precisely controls its synthesis and homeostasis. The brain cholesterol pool is almost completely separated from the rest of the body by the functional blood-brain barrier (BBB). Only a part of cholesterol pool can be exchanged with the blood circulation in the form of the oxysterol metabolites such, as 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC). Not only neurons but also blood vessels and neuroglia, constituting neurovascular unit (NVU), are crucial for the brain cholesterol metabolism and undergo precise regulation by numerous modulators, metabolites and signal molecules...
April 21, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28432017/dual-functional-nanoparticles-for-precise-drug-delivery-to-alzheimer-s-disease-lesions-targeting-mechanisms-pharmacodynamics-and-safety
#8
Xiaoyao Zheng, Chi Zhang, Qian Guo, Xu Wan, Xiayan Shao, Qingfeng Liu, Qizhi Zhang
Alzheimer's disease (AD) is the most common form of dementia and is characterized by the cerebral accumulation of extracellular amyloid plaques. In a previous study, this histopathological hallmark was used as a target on a dual-functional nanoparticle (TQNP) to deliver biotechnological drugs, such as the H102 peptide, a β-sheet breaker, to AD lesions precisely. This delivery system could reduce the amyloid-β (Aβ) burden in the brains of AD model mice, as well as ameliorated the memory impairment of the mice...
April 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28429235/regulation-of-human-brain-microvascular-endothelial-cell-adhesion-and-barrier-functions-by-memantine
#9
Fei Wang, Zhirong Zou, Yi Gong, Dong Yuan, Xun Chen, Tao Sun
Vascular risk factors have been linked to cognitive decline and dementia in the elderly. Microvascular inflammation, especially of the endothelium, may contribute to the progression of neurodegenerative events in Alzheimer's disease (AD). Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is a licensed drug used for the treatment of moderate to severe AD. However, little information is available regarding its anti-inflammatory effects on the endothelium. In this study, we investigated the effects of memantine on human brain microvascular endothelial dysfunction induced by the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α)...
April 20, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28428179/adamts13-controls-vascular-remodeling-by-modifying-vwf-reactivity-during-stroke-recovery
#10
Haochen Xu, Yongliang Cao, Xing Yang, Ping Cai, Lijing Kang, Ximin Zhu, Haiyu Luo, Lu Lu, Lixiang Wei, Xiaofei Bai, Yuanbo Zhu, Bing-Qiao Zhao, Wenying Fan
Angiogenic response is essential for ischemic brain repair. However, the mechanisms leading to postischemic neovascularization have not been established, and no therapies have been identified. The VWF-cleaving protease ADAMTS13 is required for endothelial tube formation in vitro However, there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited significantly reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) breakdown and extravascular deposits of serum proteins in the peri-infarct cortex at 14 days after stroke...
April 20, 2017: Blood
https://www.readbyqxmd.com/read/28425493/characterization-of-different-microbubbles-in-assisting-focused-ultrasound-induced-blood-brain-barrier-opening
#11
Sheng-Kai Wu, Po-Chun Chu, Wen-Yen Chai, Shih-Tsung Kang, Chih-Hung Tsai, Ching-Hsiang Fan, Chih-Kuang Yeh, Hao-Li Liu
Microbubbles (MBs) serve as a critical catalyst to amplify local cavitation in CNS capillary lumen to facilitate focused ultrasound (FUS) to transiently open the blood-brain barrier (BBB). However, limited understanding is available regarding the effect of different microbubbles to induce BBB opening. The aim of this study is to characterize different MBs on their effect in FUS-induced BBB opening. Three MBs, SonoVue, Definity, and USphere, were tested, with 0.4-MHz FUS exposure at 0.62-1.38 of mechanical index (MI) on rats...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28425480/efficient-cns-targeting-in-adult-mice-by-intrathecal-infusion-of-single-stranded-aav9-gfp-for-gene-therapy-of-neurological-disorders
#12
K Bey, C Ciron, L Dubreil, J Deniaud, M Ledevin, J Cristini, V Blouin, P Aubourg, M-A Colle
Adeno-associated virus (AAV) gene therapy constitutes a powerful tool for the treatment of neurodegenerative diseases. While AAVs are generally administered systemically to newborns in preclinical studies of neurological disorders, in adults the maturity of the blood-brain barrier (BBB) must be considered when selecting the route of administration. Delivery of AAVs into the cerebrospinal fluid (CSF) represents an attractive approach to target the central nervous system (CNS) and bypass the BBB. In this study, we investigated the efficacy of intra-CSF delivery of a single-stranded (ss) AAV9-CAG-GFP vector in adult mice via intracisternal (iCist) or intralumbar (it-Lumb) administration...
April 20, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28423515/preclinical-therapeutic-efficacy-of-a-novel-blood-brain-barrier-penetrant-dual-pi3k-mtor-inhibitor-with-preferential-response-in-pi3k-pten-mutant-glioma
#13
Dimpy Koul, Shuzhen Wang, Shaofang Wu, Norihiko Saito, Siyuan Zheng, Feng Gao, Isha Kaul, Masaki Setoguchi, Kiyoshi Nakayama, Kumiko Koyama, Yoshinobu Shiose, Erik P Sulman, Yasuhide Hirota, W K Alfred Yung
Glioblastoma (GBM) is an ideal candidate disease for signal transduction targeted therapy because the majority of these tumors harbor genetic alterations that result in aberrant activation of growth factor signaling pathways. Loss of heterozygosity of chromosome 10, mutations in the tumor suppressor gene PTEN, and PI3K mutations are molecular hallmarks of GBM and indicate poor prognostic outcomes in many cancers. Consequently, inhibiting the PI3K pathway may provide therapeutic benefit in these cancers. PI3K inhibitors generally block proliferation rather than induce apoptosis...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#14
Maria Karamita, Christopher Barnum, Wiebke Möbius, Malú G Tansey, David E Szymkowski, Hans Lassmann, Lesley Probert
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28422060/clarifying-the-ghrelin-system-s-ability-to-regulate-feeding-behaviours-despite-enigmatic-spatial-separation-of-the-ghsr-and-its-endogenous-ligand
#15
REVIEW
Alexander Edwards, Alfonso Abizaid
Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor (GHSR), a receptor found in relatively high concentrations in hypothalamic and mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can be explained by the effects of this hormone on regions of the brain that have a more permeable blood brain barrier (BBB), ghrelin produced within the periphery demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are expressed...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28420192/thioredoxin-interacting-protein-mediates-apoptosis-in-early-brain-injury-after-subarachnoid-haemorrhage
#16
Qing Zhao, Xudong Che, Hongxia Zhang, Guanping Tan, Liu Liu, Dengzhi Jiang, Jun Zhao, Xiang Xiang, Xiaochuan Sun, Zhaohui He
Early brain injury (EBI) is considered to be the major factor associated with high morbidity and mortality after subarachnoid haemorrhage (SAH). Apoptosis is the major pathological mechanism of EBI, and its pathogenesis has not been fully clarified. Here, we report that thioredoxin-interacting protein (TXNIP), which is induced by protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK), participates in EBI by promoting apoptosis. By using adult male Sprague-Dawley rats to establish SAH models, as well as Terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining, immunofluorescence, and western blot, we found that TXNIP expression significantly increased after SAH in comparison to the sham group and peaked at 48 h (up to 3...
April 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416077/blood-brain-barrier-permeability-is-regulated-by-lipid-transport-dependent-suppression-of-caveolae-mediated-transcytosis
#17
Benjamin J Andreone, Brian Wai Chow, Aleksandra Tata, Baptiste Lacoste, Ayal Ben-Zvi, Kevin Bullock, Amy A Deik, David D Ginty, Clary B Clish, Chenghua Gu
The blood-brain barrier (BBB) provides a constant homeostatic brain environment that is essential for proper neural function. An unusually low rate of vesicular transport (transcytosis) has been identified as one of the two unique properties of CNS endothelial cells, relative to peripheral endothelial cells, that maintain the restrictive quality of the BBB. However, it is not known how this low rate of transcytosis is achieved. Here we provide a mechanism whereby the regulation of CNS endothelial cell lipid composition specifically inhibits the caveolae-mediated transcytotic route readily used in the periphery...
April 11, 2017: Neuron
https://www.readbyqxmd.com/read/28415790/hyperglycemia-via-activation-of-thromboxane-a2-receptor-impairs-the-integrity-and-function-of-blood-brain-barrier-in-microvascular-endothelial-cells
#18
Zhihong Zhao, Jue Hu, Xiaoping Gao, Hui Liang, Haiya Yu, Suosi Liu, Zhan Liu
Diabetes is one of high risk factors for cardio- and cerebra-vascular diseases, including stroke, atherosclerosis and hypertension. This study was conducted to elucidate whether and how thromboxane receptor (TPr) activation contributes to blood-brain barrier (BBB) dysfunction in diabetes. Human brain microvascular endothelial cells (HBMECs) were cultured. The levels of phosphorylated endothelial nitric oxide synthase (eNOS) at Ser1177 (p-eNOS) and Akt at Ser473 (p-Akt) were assayed by western blot. Exposure of HBMECs to either high glucose (HG) or thromboxane A2 (TxA2) mimetic U46619, significantly reduced p-eNOS and p-Akt...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415681/a-reproducible-model-of-intramedullary-spinal-cord-tumor-in-rats-bearing-rg2-cells
#19
Yuandong Zhuang, Wei Zhao, Weiqiang Zhang, Hao Wei, Xinming Huang, Gangfeng Cai, Chaofeng Fu, Chunhua Wang, Rui Wang, Songsheng Shi, Weizhong Yang, Chunmei Chen
Intramedullary spinal cord tumors (IMSCTs) are lethal diseases to many patients. The lack of adequate animal model has hampered the development of novel treatments. In the current study, a rodent intramedullary glioma model is established to study IMSCT progression. Fischer 344 rats received a intramedullary implantation of RG2 glioma cells. The neurological state of each rat was evaluated on daily basis using the Basso, Beattie and Bresnahan (BBB) scale. Rats implanted with RG2 cells developed significant hind limb paraplegia 20 days after implantation...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413983/peripheral-blood-mononuclear-cells-of-alzheimer-s-disease-patients-control-ccl4-and-cxcl10-levels-in-a-human-blood-brain-barrier-model
#20
Julie Vérité, Thierry Janet, Adrien Julian, Damien Chassaing, Guylène Page, Marc Paccalin
BACKGROUND: Alzheimer's disease (AD) is accompanied by a neuroinflammation triggering chemoattractant signals towards peripheral blood mononuclear cells (PBMCs), in turn could reduce amyloid plaques after transmigration through the blood brain barrier (BBB). But the chemotactic environment remains unclear. OBJECTIVE: To analyze five chemokines known to be involved in AD in three different cellular models to better understand the cellular and molecular interactions in the BBB...
April 17, 2017: Current Alzheimer Research
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