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brain endothelium

M R Lee, R D Jayant
The blood-brain barrier (BBB) is a structural and functional barrier between the interstitial fluid of the brain and the blood; the barrier maintains the precisely controlled biochemical environment that is necessary for neural function. This constellation of endothelial cells, macrophages, pericytes, and astrocytes forms the neurovascular unit which is the structural and functional unit of the blood-brain barrier. Peptides enter and exit the CNS by transport systems expressed by the capillary endothelial cells of the neurovascular unit...
December 10, 2018: Cell and Tissue Research
Ciro De Luca, Anna Maria Colangelo, Lilia Alberghina, Michele Papa
Coagulation and the immune system interact in several physiological and pathological conditions, including tissue repair, host defense, and homeostatic maintenance. This network plays a key role in diseases of the central nervous system (CNS) by involving several cells (CNS resident cells, platelets, endothelium, and leukocytes) and molecular pathways (protease activity, complement factors, platelet granule content). Endothelial damage prompts platelet activation and the coagulation cascade as the first physiological step to support the rescue of damaged tissues, a flawed rescuing system ultimately producing neuroinflammation...
2018: Frontiers in Cellular Neuroscience
Bapurao Surnar, Uttara Basu, Bhabatosh Banik, Anis Ahmad, Brian Marples, Nagesh Kolishetti, Shanta Dhar
The success of nanoparticle-mediated delivery of antioxidant and antiinflammatory-based neuroprotectants to the brain to improve neuronal functions in neurodegenerative diseases has demonstrated lesser impact instead of achieving its full potential. We hypothesized that these failures were due to a combination of parameters, such as: ( i ) unavailability of a delivery vehicle, which can reproducibly and efficiently transport through the brain capillary endothelium; ( ii ) inefficient uptake of therapeutic nanoparticles in the neuronal cell population; and ( iii ) limited ability of a single nanoparticle to cross the two most-impermeable biological barriers, the blood-brain barrier and mitochondrial double membrane, so that a nanoparticle can travel through the brain endothelial barrier to the mitochondria of target cells where oxidative damage is localized...
December 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
Abha Sahni, Hema P Narra, Jignesh Patel, Sanjeev K Sahni
Microvascular endothelial cells (ECs) represent the primary target cells during human rickettsioses and respond to infection via the activation of immediate⁻early signaling cascades and the resultant induction of gene expression. As small noncoding RNAs dispersed throughout the genome, microRNAs (miRNAs) regulate gene expression post-transcriptionally to govern a wide range of biological processes. Based on our recent findings demonstrating the involvement of fibroblast growth factor receptor 1 (FGFR1) in facilitating rickettsial invasion into host cells and published reports suggesting miR-424 and miR-503 as regulators of FGF2/FGFR1, we measured the expression of miR-424 and miR-503 during R...
December 1, 2018: Cells
Yoshiaki Ando, Hideshi Okada, Genzou Takemura, Kodai Suzuki, Chihiro Takada, Hiroyuki Tomita, Ryogen Zaikokuji, Yasuaki Hotta, Nagisa Miyazaki, Hirohisa Yano, Isamu Muraki, Ayumi Kuroda, Hirotsugu Fukuda, Yuki Kawasaki, Haruka Okamoto, Tomonori Kawaguchi, Takatomo Watanabe, Tomoaki Doi, Takahiro Yoshida, Hiroaki Ushikoshi, Shozo Yoshida, Shinji Ogura
Endothelial glycocalyx coats healthy vascular endothelium and plays an important role in vascular homeostasis. Although cerebral capillaries are categorized as continuous, as are those in the heart and lung, they likely have specific features related to their function in the blood brain barrier. To test that idea, brains, hearts and lungs from C57BL6 mice were processed with lanthanum-containing alkaline fixative, which preserves the structure of glycocalyx, and examined using scanning and transmission electron microscopy...
November 30, 2018: Scientific Reports
Sen Yin, Wenwu Bai, Peng Li, Xu Jian, Tichao Shan, Zhenyu Tang, Xuejiao Jing, Song Ping, Quanzhong Li, Zhang Miao, Shuangxi Wang, Wensheng Ou, Jianchun Fei, Tao Guo
OBJECTIVE: Vascular dementia is the second leading cause of dementia, which is strongly associated with diabetes. Ectopic expression of miR-133a in endothelial cells is involved in endothelial dysfunction in diabetes. Whether berberine, as a natural product in Coptis chinensis, improves vascular dementia induced by diabetes remains unknown. METHODS: Diabetes and subsequent vascular dementia were induced in rats by injecting streptozotocin (50 mg/kg/day) for five consecutive days...
November 26, 2018: Clinical and Experimental Hypertension: CHE
Kevin Kruse, Quinn S Lee, Ying Sun, Jeff Klomp, Xiaoyan Yang, Fei Huang, Mitchell Y Sun, Shuangping Zhao, Zhigang Hong, Stephen M Vogel, Jae-Won Shin, Deborah E Leckband, Leon M Tai, Asrar B Malik, Yulia A Komarova
Vascular endothelial (VE)-cadherin forms homotypic adherens junctions (AJs) in the endothelium, whereas N-cadherin forms heterotypic adhesion between endothelial cells and surrounding vascular smooth muscle cells and pericytes. Here we addressed the question whether both cadherin adhesion complexes communicate through intracellular signaling and contribute to the integrity of the endothelial barrier. We demonstrated that deletion of N-cadherin ( Cdh2 ) in either endothelial cells or pericytes increases junctional endothelial permeability in lung and brain secondary to reduced accumulation of VE-cadherin at AJs...
November 21, 2018: Journal of Cell Biology
Raymond Wong, Nikolett Lénárt, Laura Hill, Lauren Toms, Graham Coutts, Bernadett Martinecz, Eszter Császár, Gábor Nyiri, Athina Papaemmanouil, Ari Waisman, Werner Müller, Markus Schwaninger, Nancy Rothwell, Sheila Francis, Emmanuel Pinteaux, Adam Denes, Stuart M Allan
The cytokine interleukin-1 (IL-1) is a key contributor to neuroinflammation and brain injury, yet mechanisms by which IL-1 triggers neuronal injury remain unknown. Here we induced conditional deletion of IL-1R1 in brain endothelial cells, neurons and blood cells to assess site-specific IL-1 actions in a model of cerebral ischaemia in mice. Tamoxifen treatment of IL-1R1 floxed (fl/fl ) mice crossed with mice expressing tamoxifen-inducible Cre-recombinase under the Slco1c1 promoter resulted in brain endothelium-specific deletion of IL-1R1 and a significant decrease in infarct size (29%), blood-brain barrier (BBB) breakdown (53%) and neurological deficit (40%) compared to vehicle-treated or control (IL-1R1fl/fl ) mice...
November 16, 2018: Brain, Behavior, and Immunity
Yasushi Iwasaki, Rina Hashimoto, Yufuko Saito, Ikuko Aiba, Akira Inukai, Akio Akagi, Maya Mimuro, Hiroaki Miyahara, Tetsuyuki Kitamoto, Mari Yoshida
An 83-year-old Japanese man presented with gait disturbance followed by rapidly-progressive cognitive impairment. Magnetic resonance diffusion-weighted images showed extensive hyperintense regions in the cerebral cortex. Four weeks after symptom onset, myoclonus appeared, and the patient developed difficulty swallowing; intravenous peripheral continuous infusions without vitamin supplementation were administered during the last two months of the patient's life. The patient reached the akinetic mutism state and died 12 weeks after symptom onset due to sepsis...
November 8, 2018: Prion
Ji-Yue Wen, Shan-Shan Gao, Fang-Lin Chen, Shuo Chen, Mei Wang, Zhi-Wu Chen
The role of CSE-produced H2 S on cerebrovascular relaxation and cerebral ischemia-reperfusion (I/R) injury was investigated using CSE knockout (CSE-/- ) and wild-type (CSE+/+ ) mice. The relaxation of the cerebral basilar artery (BA) to CSE-produced H2 S and its mechanism were detected. The results revealed that both NaHS, a donor of exogenous H2 S, and ROCK inhibitor Y27632 could induce significant relaxation of the BA, but the relaxation of the BA to NaHS was significantly attenuated by Y27632. In addition, removal of endothelium could reduce the relaxation of the BA to Y27632; CSE knockout also significantly attenuated Y27632-induced BA relaxation with endothelium rather than without endothelium...
November 29, 2018: ACS Chemical Neuroscience
Jun Han, Hang-Hang Xu, Xiao-Long Chen, Hao-Ran Hu, Kun-Mei Hu, Zhi-Wu Chen, Guo-Wei He
Background: Total flavonoids of Rhododendron (TFR) is extracted from Rhododendron, a herbal medicine widely used in China. The main components are flavone compounds such as warfarin, rutin, quercetin, and hyperoside. We investigated the role of TRPV4 channel in the TFR induced endothelium-dependent hyperpolarizing factor- (EDHF-) mediated responses against ischemia/reperfusion injury (IR) in cerebral IR (CIR) rats. Methods: The morphological changes of cerebral cortex, the relaxation of cerebral basal artery (CBA), and cell membrane potential recording were studied in CIR rats...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Ji-Yue Wen, Mei Wang, Ya-Nan Li, Hui-Hui Jiang, Xuan-Jun Sun, Zhi-Wu Chen
This study was undertaken to demonstrate the vascular protection of exogenous and endogenous hydrogen sulfide (H2 S) on cerebral ischemia/reperfusion (I/R) injury. The effect of H2 S on cerebrovascular dysfunction in middle cerebral artery (MCA) and neuronal damage were measured after cerebral I/R induced by transient middle cerebral artery occlusion (MCAO) in cystathionine c-lyase (CSE) knockdown and wild-type rats. The effect of sodium hydrosulfide (NaHS, donor of exogenous H2 S), L-cysteine (L-Cys, substrate of endogenous H2 S), and endothelium cells on the responses of isolated MCA derived from non-ischemic rats was also evaluated to assess the underlying mechanism of H2 S-mediate cerebral vasodilation...
2018: Frontiers in Neurology
Dorota Piekna-Przybylska, Kavyasri Nagumotu, Danielle M Reid, Sanjay B Maggirwar
Reduced pericytes' coverage of endothelium in the brain is one of the structural changes leading to breach of the blood-brain barrier during HIV infection. We previously showed in central memory T (TCM ) cells that HIV latency increases cellular susceptibility to DNA damage. In this study, we investigated susceptibility of primary brain pericytes infected with HIV-1 to DNA damage in response to glutamate and TNF-α, both known to induce neuronal death during chronic inflammatory conditions. To infect pericytes, we used a single-cycle HIV-1 pseudotyped with VSV-G envelope glycoprotein and maintained the cultures until latency was established...
November 6, 2018: Journal of Neurovirology
Yuan Tang, Fariborz Soroush, Shuang Sun, Elisabetta Liverani, Jordan C Langston, Qingliang Yang, Laurie E Kilpatrick, Mohammad F Kiani
BACKGROUND: Neuroinflammation often develops in sepsis leading to activation of cerebral endothelium, increased permeability of the blood-brain barrier (BBB), and neutrophil infiltration. We have identified protein kinase C-delta (PKCδ) as a critical regulator of the inflammatory response and demonstrated that pharmacologic inhibition of PKCδ by a peptide inhibitor (PKCδ-i) protected endothelial cells, decreased sepsis-mediated neutrophil influx into the lung, and prevented tissue damage...
November 6, 2018: Journal of Neuroinflammation
Xin Zhang, Kaikai Ding, Jian Wang, Xingang Li, Peng Zhao
Glioblastoma multiforme (GBM) is the most common and aggressive primary human brain tumor. Although comprehensive therapies combining radiotherapy and chemotherapy after surgery can prolong survival, the prognosis is still poor with a median survival of only 14.6 months. Chemoresistance is one of the major causes of relapse as well as poor survival in glioma patients. Therefore, novel strategies to overcome chemoresistance are desperately needed for improved treatment of human GBM. Recent studies have demonstrated that the tumor microenvironment plays a critical role in the chemoresistance of various tumor types, which makes it a suitable target in anti-cancer therapies, as well as a valuable biomarker for prognostic purposes...
November 1, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Qariani Hajare, Khmamouche Mehdi
Wilson's disease is a copper toxicosis characterized by an overload in tissue copper (mainly hepatic, cerebral and pericorneal). It is caused by ATP7B mutations which incorporate copper into ceruloplasmin in the liver and pass out excess copper into the bile. This disease can be adequately treated if diagnosed early. The challenge is to diagnose it in the early stage of liver disease, before it becomes multisystemic. We report the case of a 19-year old female patient with Wilson's disease with multisytemic involvement: mucocutaneous pallor, intermittent hand tremor, that started when she was 16 years, hepatitis complicated by ascites, neurological disorder, such as postural tremor of the arms and the legs...
2018: Pan African Medical Journal
Panfeng Fu, Mark Shaaya, Anantha Harijith, Jeffrey R Jacobson, Andrei Karginov, Viswanathan Natarajan
Sphingolipids, first described in the brain in 1884, are important structural components of biological membranes of all eukaryotic cells. In recent years, several lines of evidence support the critical role of sphingolipids such as sphingosine, sphingosine-1-phosphate (S1P), and ceramide as anti- or pro-inflammatory bioactive lipid mediators in a variety of human pathologies including pulmonary and vascular disorders. Among the sphingolipids, S1P is a naturally occurring agonist that exhibits potent barrier enhancing property in the endothelium by signaling via G protein-coupled S1P1 receptor...
2018: Current Topics in Membranes
Franca Orsini, Stefano Fumagalli, Eszter Császár, Krisztina Tóth, Daiana De Blasio, Rosalia Zangari, Nikolett Lénárt, Ádám Dénes, Maria-Grazia De Simoni
Objective- Circulating complement factors are activated by tissue damage and contribute to acute brain injury. The deposition of MBL (mannose-binding lectin), one of the initiators of the lectin complement pathway, on the cerebral endothelium activated by ischemia is a major pathogenic event leading to brain injury. The molecular mechanisms through which MBL influences outcome after ischemia are not understood yet. Approach and Results- Here we show that MBL-deficient (MBL-/- ) mice subjected to cerebral ischemia display better flow recovery and less plasma extravasation in the brain than wild-type mice, as assessed by in vivo 2-photon microscopy...
November 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Dan Shi, Man Qi, Liping Zhou, Xiang Li, Le Ni, Changming Li, Tianyou Yuan, Yunqian Wang, Yongli Chen, Chaoyue Hu, Dandan Liang, Li Li, Yi Liu, Jun Li, Yi-Han Chen
Objective- Mitochondria are the important yet most underutilized target for cardio-cerebrovascular function integrity and disorders. The Tom (translocases of outer membrane) complex are the critical determinant of mitochondrial homeostasis for making organs acclimate physiological and pathological insults; however, their roles in the vascular system remain unknown. Approach and Results- A combination of studies in the vascular-specific transgenic zebrafish and genetically engineered mice was conducted. Vascular casting and imaging, endothelial angiogenesis, and mitochondrial protein import were performed to dissect potential mechanisms...
November 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Qiuchen Zhao, Zhanyang Yu, Fang Zhang, Lena Huang, Changhong Xing, Ning Liu, Yun Xu, Xiaoying Wang
Histone deacetylase 3 (HDAC3), a member of class I HDAC, regulates a wide variety of normal and abnormal physiological functions. Recent experimental studies suggested that inhibition of HDAC3 may increase acetylation of certain key signaling regulating proteins such as peroxisome proliferator-activated receptor γ (PPARγ), which plays a crucial role in modulating cerebrovascular function and integrity. However, the role of HDAC3 inhibition in cerebrovascular endothelium function under pathological condition has not been fully investigated...
October 22, 2018: Journal of Neurochemistry
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