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Author: Leon Smyth
Publisher:
ISBN:
Category :
Languages : en
Pages : 466
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Book Description
The blood-brain barrier (BBB) is an important protective structure that restricts the free passage of blood components and circulating immune cells into the brain. The BBB is primarily composed of endothelial cells that line the inside of the vessel, and is surrounded by pericytes that perform critical roles in its formation and maintenance. In this project, I aimed to examine aspects of inflammatory signalling at the BBB using primary human brain pericytes and endothelia. Initially, pericytes were characterised in human brain tissue to develop a panel of markers for pericytes in vitro. Characterisation studies validated that in vitro cultures of pericytes recapitulated their in situ phenotype, as well as identifying two novel markers of vascular smooth muscle cell phenotype in situ and in vitro. A protocol for the isolation of primary human brain endothelia was then developed to study the interactions of pericytes and endothelia in vitro, and these cultures were shown to retain their unique brain endothelial phenotype. Using cultures of pericytes and endothelia, differences in the inflammatory response of these two cell types were identified, including unique secretions, and differential sensitivity to inflammatory stimuli. Subsequently, the role of platelet-derived growth factor-BB (PDGF-BB) was investigated in greater detail. PDGF-BB was found to cause a proliferative response in brain pericytes, as has been found previously, but also induced the expression of inflammation-related secretions. The pathways through which this inflammatory response was mediated were dissected using genetic and pharmacological inhibitors. Interestingly, it was found that PDGF-BB altered pericyteendothelial interactions, stopping pericytes from strengthening the endothelial barrier. The role of PDGF-BB was investigated further in co-cultures, incorporating astrocytes, microglia, endothelia, and pericytes. It was observed that PDGF-BB improves the formation of blood vessel-like endothelial cords in vitro due to reduced cell death and increased expression of angiogenesis-associated molecules, reminiscent of its effects in vivo. The BBB is a critical structure in the brain, but has not yet been targeted to treat disease. Together these findings provide novel insights into cell-cell signalling at the BBB, and how these interactions are modified during inflammatory conditions. Because BBB damage and neuroinflammation are critical disease processes in neurological diseases, the factors that govern neuroinflammation at the BBB present potential drug targets to prevent the progression of AD.
Author: Leon Smyth
Publisher:
ISBN:
Category :
Languages : en
Pages : 466
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Book Description
The blood-brain barrier (BBB) is an important protective structure that restricts the free passage of blood components and circulating immune cells into the brain. The BBB is primarily composed of endothelial cells that line the inside of the vessel, and is surrounded by pericytes that perform critical roles in its formation and maintenance. In this project, I aimed to examine aspects of inflammatory signalling at the BBB using primary human brain pericytes and endothelia. Initially, pericytes were characterised in human brain tissue to develop a panel of markers for pericytes in vitro. Characterisation studies validated that in vitro cultures of pericytes recapitulated their in situ phenotype, as well as identifying two novel markers of vascular smooth muscle cell phenotype in situ and in vitro. A protocol for the isolation of primary human brain endothelia was then developed to study the interactions of pericytes and endothelia in vitro, and these cultures were shown to retain their unique brain endothelial phenotype. Using cultures of pericytes and endothelia, differences in the inflammatory response of these two cell types were identified, including unique secretions, and differential sensitivity to inflammatory stimuli. Subsequently, the role of platelet-derived growth factor-BB (PDGF-BB) was investigated in greater detail. PDGF-BB was found to cause a proliferative response in brain pericytes, as has been found previously, but also induced the expression of inflammation-related secretions. The pathways through which this inflammatory response was mediated were dissected using genetic and pharmacological inhibitors. Interestingly, it was found that PDGF-BB altered pericyteendothelial interactions, stopping pericytes from strengthening the endothelial barrier. The role of PDGF-BB was investigated further in co-cultures, incorporating astrocytes, microglia, endothelia, and pericytes. It was observed that PDGF-BB improves the formation of blood vessel-like endothelial cords in vitro due to reduced cell death and increased expression of angiogenesis-associated molecules, reminiscent of its effects in vivo. The BBB is a critical structure in the brain, but has not yet been targeted to treat disease. Together these findings provide novel insights into cell-cell signalling at the BBB, and how these interactions are modified during inflammatory conditions. Because BBB damage and neuroinflammation are critical disease processes in neurological diseases, the factors that govern neuroinflammation at the BBB present potential drug targets to prevent the progression of AD.
Author: Ruth Lyck
Publisher: Springer
ISBN: 3319455141
Category : Medical
Languages : en
Pages : 288
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Book Description
This PIR volume presents a comprehensive collection of reviews that focus on the role of the blood-brain barrier (BBB) during steady-state and inflamed conditions. Within the central nervous system (CNS) the constantly changing bloodstream is strictly separated from the CNS parenchyma by the BBB. However, viruses, bacteria, parasites and auto-aggressive immune cells can penetrate the barrier and significantly contribute to CNS inflammation. The BBB can actively contribute to neuroinflammation by presentation of chemokines, expression of cell adhesion molecules and alterations of barrier properties. As such, understanding the role of the BBB under healthy and pathological conditions is essential to the development of new drugs to efficiently combat inflammatory diseases of the CNS.
Author: Anna Eskilsson
Publisher:
ISBN: 9789179299361
Category : Electronic books
Languages : en
Pages : 55
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Book Description
Author: Katerina Dorovini-Zis
Publisher: CRC Press
ISBN: 1498727069
Category : Medical
Languages : en
Pages : 418
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Book Description
Located at the interface between blood and the brain, the blood-brain barrier is a dynamic permeability barrier formed by a continuous layer of specialized endothelial cells endowed with important permeability, transport, and regulatory functions that both protect the internal milieu of the brain and allow essential nutrients to be transported into
Author: Arthur Liesz
Publisher: Frontiers Media SA
ISBN: 2889196917
Category : Neurosciences. Biological psychiatry. Neuropsychiatry
Languages : en
Pages : 286
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Book Description
Mechanisms of brain-immune interactions became a cutting-edge topic in systemic neurosciences over the past years. Acute lesions of the brain parenchyma, particularly, induce a profound and highly complex neuroinflammatory reaction with similar mechanistic properties between differing disease paradigms like ischemic stroke, intracerebral hemorrhage (ICH) and traumatic brain injury (TBI). Resident microglial cells sense tissue damage and initiate inflammation, activation of the endothelial brain-immune interface promotes recruitment of systemic immune cells to the brain and systemic humoral immune mediators (e.g. complements and cytokines) enter the brain through the damaged blood-brain barrier. These cellular and humoral constituents of the neuroinflammatory reaction to brain injury contribute substantially to secondary brain damage and neurodegeneration. Diverse inflammatory cascades such as pro-inflammatory cytokine secretion of invading leukocytes and direct cell-cell-contact cytotoxicity between lymphocytes and neurons have been demonstrated to mediate the inflammatory ‘collateral damage’ in models of acute brain injury. Besides mediating neuronal cell loss and degeneration, secondary inflammatory mechanisms also contribute to functional modulation of neurons and the impact of post-lesional neuroinflammation can even be detected on the behavioral level. The contribution of several specific immune cell subpopulations to the complex orchestration of secondary neuroinflammation has been revealed just recently. However, the differential vulnerability of specific neuronal cell types and the molecular mechanisms of inflammatory neurodegeneration are still elusive. Furthermore, we are only on the verge of characterizing the control of long-term recovery and neuronal plasticity after brain damage by inflammatory pathways. Yet, a more detailed but also comprehensive understanding of the multifaceted interaction of these two supersystems is of direct translational relevance. Immunotherapeutic strategies currently shift to the center of translational research in acute CNS lesion since all clinical trials investigating direct neuroprotective therapies failed. To advance our knowledge on brain-immune communications after brain damage an interdisciplinary approach covered by cellular neuroscience as well as neuroimmunology, brain imaging and behavioral sciences is crucial to thoroughly depict the intricate mechanisms.
Author: Gonzalo Emiliano Aranda Abreu
Publisher: BoD – Books on Demand
ISBN: 9535134515
Category : Medical
Languages : en
Pages : 320
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Book Description
"Mechanisms of Neuroinflammation" book explains how the neuronal cells become swollen at the moment of the blood-brain barrier disruption and how they lose their immunological isolation. A cascade of cytokines and immune cells from the bloodstream enters the nervous system, inflaming neurons and activating the glia. This produces a neuroinflammatory process that can generate different neurodegenerative diseases. Better understanding of mechanisms that are activated at the time when the damage to the brain occurs could lead to the development of suitable therapies that revert the neuronal inflammation and thus prevent further damage to the nervous system.
Author: Saparna Pai
Publisher: Frontiers Media SA
ISBN: 2889453642
Category :
Languages : en
Pages : 110
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Book Description
Inflammation of the CNS can have devastating, long-lived, and in some cases fatal consequences for patients. The stimuli that can induce CNS inflammation are diverse, and include infectious agents, autoimmune responses against CNS-expressed antigens, and sterile inflammation following ischemia or traumatic injury. In these conditions, cells of the immune system play central roles in promulgation and resolution of the inflammatory response. However, the immunological mechanisms at work in these diverse responses differ according to the nature of the response. Our understanding of the actions of immune cells in the CNS has been restricted by the difficulty in visualising leukocytes as they undergo recruitment from the cerebral microvasculature and following their entry into the CNS parenchyma. However, advances in in vivo microscopy over the last 10-15 years have overcome many of these difficulties, and studies using these forms of microscopy have revealed a wealth of new information regarding the cellular and molecular mechanisms of CNS inflammation. This Research Topic brings together state of the art reviews examining the use of in vivo imaging in investigating inflammation and leukocyte behaviour in the CNS. Papers in this Research Topic describe how in vivo microscopy has increased our understanding of the actions of immune cells in the inflamed CNS, following various stimuli including autoimmunity, infection and sterile inflammation.
Author: Katerina Dorovini-Zis
Publisher: CRC Press
ISBN: 1498727093
Category : Medical
Languages : en
Pages : 390
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Book Description
Located at the interface between blood and the brain, the blood-brain barrier is a dynamic permeability barrier formed by a continuous layer of specialized endothelial cells endowed with important permeability, transport, and regulatory functions that both protect the internal milieu of the brain and allow essential nutrients to be transported into
Author: Giora Z. Feuerstein
Publisher: Springer
ISBN: 3034882971
Category : Medical
Languages : en
Pages : 351
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Book Description
Stroke is a leading cause of death in developed countries. However, current therapeutic strategies for stroke have been largely unsuccessful. One possible explanation is that research and pharmacological management have focused on very early events in brain ischemia. New research has shown that brain ischemia and trauma elicit strong inflammatory reactions driven by both external and brain cells. The recognition of inflammation as a fundamental response to brain ischemia provides novel opportunities for new anti-inflammatory therapies. For the first time, an international body of researchers presents the latest findings about the cellular and humoral aspects of immune and inflammatory reactions in the brain. The work may have an impact on the treatment of neuroinjuries and ancillary brain diseases, and increase the understanding of the roles infections and immune reactions play in the brain milieu.
Author: David Kobiler
Publisher: Springer Science & Business Media
ISBN: 9780306467080
Category : Medical
Languages : en
Pages : 450
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Book Description
1. Overview of the Structure and Function of the Blood-Brain Barrier in vivo; J. Fenstermacher, et al. 2. Expression and Modulation of Blood-Brain Monocarboxylate Transporters; L.R. Drewes, et al. 3. Neuroprotective and Detoxifying Mechanisms at the Blood-Brain Interfaces; J.-F. Ghersi-Egea, et al. 4. Measurement and Prediction of Blood-Brain Barrier Permeability: In vivo, in silico and in vitro approaches; N.J. Abbott, et al. 5. Recent Advances in the Development of Cell Culture Models for the Blood-Brain and Blood-CSF-Barrier; T. Nitz, et al. 6. Gene Expression Changes and Progression to a BBB Phenotype in a Dynamic Model of the BBB; S.Y. Desai, et al. 7. Novel Endothelial-Mediated Responses Associated with Micro-Circulation and BBB Function; M. Spatz, et al. 8. Modulators of Blood-Brain Barrier (BBB) Permeability: In Vitro and In Vivo Drug Transport to the Brain; A.G. de Boer, et al. 9. Controlled Modulation of the Blood-Brain and Blood-Tumor Barrier Using Novel Lipid Mimetic Compounds; M. Polyak, et al. 10. Carbon Dioxide Gas as an Angiographic Contrast Agent in the Cerebral Circulation; A.J. Wilson, M.M. Boxer. 11. Diffusion MRI and Q-Space Diffusion MRI: From Cerebral Ischemia to Multiple Sclerosis and Beyond; Y. Cohen, et al. 12. Brain Iron Uptake and Transport in Animal Model of Iron Deficiency, Tardive Dyskinesia and Neurodegenerative Diseases; M.B.H. Youdin, et al. 13. Stress, Pyridostigmine and the Blood-Brain Barrier; E. Grauer. 14. Transcytosis and Signalling of Pneumococci at the Blood-Brain Barrier; J.R. Weber, E.I. Tuomanen. 15. Entry of Viruses into the Central Nervous System; J.K. Fazakerley. 16. An Animal Model for the Study of BBB Modulators; D. Kobiler, et al. 17. Physiological Pathways Responsible for the Breakdown of the Blood-Brain Barrier During Viral Encephalitis; C.S. Reiss, N. Chen. 18. Gene Transfer to the Salivary Glands: Application in Gene Therapy; E. Shai, et al. 19. The Effect of Hyperosmotic Blood-Brain Barrier Disruption on Experimental Autoimmune Encephalomyelitis; H. Ovadia, et al. 20. Direct In Vivo Evidence for &agr;4-Integrin Mediated Interaction of Encephalitogenic T Cells with Endothelial VCAM-1 in the Spinal Cord White Matter Using Intravital Fluorescence Videomicroscopy; B. Engelhardt, et al. 21. The Blood-Brain Barrier in Immune Mediated Diseases of the Central Nervous System; S. Miron, A. Achiron. 22. Strategies for Increasing Drug Delivery to the Brain: Lessons Derived from Treatment of Brain Tumors; Tl. Siegal. 23. Intraarterial Therpy With or Without Radiation Therapy for Patients with Brain Tumors; S. Madajewicz, et al. 24. Optimizing Drugs for Brain Action; N.H. Greig, et al. 25. The Role of Plasma Protein Binding in Drug Delivery to Brain; Q.R. Smith, et al. 26. Issues Related to Intranasal Delivery of Neuropeptides to Temporal Lobe Targets; M.J. Kubek, et al. 27. Synthesis of Poly(Carboxyphenoxypropane-Sebacic Anhydride) for the Delivery of Drugs to the Brain; A.J. Domb, M. Kubek. 28. Intranasal Delivery of Bioactive Peptides or Peptide Analogues Enhances Spatial Memory and Protects Against Cholinergic Deficits; I. Gozes, et al. 29. Role of Inflammation in Stroke: Benefits or H
