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Tissue Barriers Oct 2017The blood brain barrier is a necessity for cerebral homeostasis and response to environmental insult, thus loss in functionality with age creates opportunities for... (Review)
Review
The blood brain barrier is a necessity for cerebral homeostasis and response to environmental insult, thus loss in functionality with age creates opportunities for disease to arise in the aged brain. Understanding how the barrier is developed and maintained throughout the earlier years of adult life can identify key processes that may have beneficial applications in the restoration of the aged brain. With an unprecedented increasing global aged population, the prevention and treatment of age-associated disorders has become a rising healthcare priority demanding novel approaches for the development of therapeutic strategies. The aging cardiovascular system has long been recognised to be a major factor in age-associated diseases such as stroke, atherosclerosis and cardiac arrest. Changes in the highly specialised cerebral vasculature may similarly drive neurodegenerative and neuropsychiatric disease.
Topics: Aging; Animals; Atherosclerosis; Blood-Brain Barrier; Brain; Humans; Stroke; Tight Junctions
PubMed: 28956691
DOI: 10.1080/21688370.2017.1373897 -
Seminars in Cell & Developmental Biology Feb 2015Essential requisite for the preservation of normal brain activity is to maintain a narrow and stable homeostatic control in the neuronal environment of the CNS. Blood... (Review)
Review
Essential requisite for the preservation of normal brain activity is to maintain a narrow and stable homeostatic control in the neuronal environment of the CNS. Blood flow alterations and altered vessel permeability are considered key determinants in the pathophysiology of brain injuries. We will review the present-day literature on the anatomy, development and physiological mechanisms of the blood-brain barrier, a distinctive and tightly regulated interface between the CNS and the peripheral circulation, playing a crucial role in the maintenance of the strict environment required for normal brain function.
Topics: Animals; Biological Transport; Blood-Brain Barrier; Brain; Endothelial Cells; Humans; Pharmaceutical Preparations
PubMed: 25681530
DOI: 10.1016/j.semcdb.2015.01.002 -
American Journal of Physiology. Cell... Feb 2019Ischemicstroke is a leading cause of death and disability in the United States, but recent advances in treatments [i.e., endovascular thrombectomy and tissue plasminogen... (Review)
Review
Ischemicstroke is a leading cause of death and disability in the United States, but recent advances in treatments [i.e., endovascular thrombectomy and tissue plasminogen activator (t-PA)] that target the stroke-causing blood clot, while improving overall stroke mortality rates, have had much less of an impact on overall stroke morbidity. This may in part be attributed to the lack of therapeutics targeting reperfusion-induced injury after the blood clot has been removed, which, if left unchecked, can expand injury from its core into the surrounding at risk tissue (penumbra). This occurs in two phases of increased permeability of the blood-brain barrier, a physical barrier that under physiologic conditions regulates brain influx and efflux of substances and consists of tight junction forming endothelial cells (and transporter proteins), astrocytes, pericytes, extracellular matrix, and their integrin cellular receptors. During, embryonic development, maturity, and following stroke reperfusion, cerebral vasculature undergoes significant changes including changes in expression of integrins and degradation of surrounding extracellular matrix. Integrins, heterodimers with α and β subunits, and their extracellular matrix ligands, a collection of proteoglycans, glycoproteins, and collagens, have been modestly studied in the context of stroke compared with other diseases (e.g., cancer). In this review, we describe the effect that various integrins and extracellular matrix components have in embryonic brain development, and how this changes in both maturity and in the poststroke environment. Particular focus will be on how these changes in integrins and the extracellular matrix affect blood-brain barrier components and their potential as diagnostic and therapeutic targets for ischemic stroke.
Topics: Animals; Astrocytes; Blood-Brain Barrier; Endothelial Cells; Extracellular Matrix; Humans; Integrins; Permeability; Stroke; Tight Junctions
PubMed: 30462535
DOI: 10.1152/ajpcell.00151.2018 -
International Journal of Molecular... Nov 2018The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic... (Review)
Review
The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria, and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the cerebral lymphatic functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in brain drainage, clearance, and recovery is still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on the connective bridge between the opening of a blood⁻brain barrier and activation of the meningeal lymphatic clearance. The ability to stimulate the lymph flow in the brain, is likely to play an important role in developing future innovative strategies in neurorehabilitation therapy.
Topics: Animals; Blood-Brain Barrier; Humans; Lymphatic System; Neurological Rehabilitation
PubMed: 30513598
DOI: 10.3390/ijms19123818 -
Tissue Barriers 2016The microvasculature of the brain forms a protective blood-brain barrier (BBB) that ensures a homeostatic environment for the central nervous system (CNS), which is... (Review)
Review
The microvasculature of the brain forms a protective blood-brain barrier (BBB) that ensures a homeostatic environment for the central nervous system (CNS), which is essential for optimal brain functioning. The barrier properties of the brain endothelial cells are maintained by cells surrounding the capillaries, such as astrocytes and pericytes. Together with the endothelium and a basement membrane, these supporting cells form the neurovascular unit (NVU). Accumulating evidence indicates that the supporting cells of the NVU release a wide variety of soluble factors that induce and control barrier properties in a concentration-dependent manner. The current review provides a comprehensive overview of how such factors, called morphogens, influence BBB integrity and functioning. Since impaired BBB function is apparent in numerous CNS disorders and is often associated with disease severity, we also discuss the potential therapeutic value of these morphogens, as they may represent promising therapies for a wide variety of CNS disorders.
Topics: Animals; Blood-Brain Barrier; Humans; Intercellular Signaling Peptides and Proteins; Neurodegenerative Diseases; Signal Transduction
PubMed: 27141417
DOI: 10.1080/21688370.2015.1090524 -
International Review of Neurobiology 2022Alcohol is the most commonly used drug of abuse in the world and binge drinking is especially harmful to the brain, though the mechanisms by which alcohol compromises... (Review)
Review
Alcohol is the most commonly used drug of abuse in the world and binge drinking is especially harmful to the brain, though the mechanisms by which alcohol compromises overall brain health remain somewhat elusive. A number of brain diseases and pathological states are accompanied by perturbations in Blood-Brain Barrier (BBB) function, ultimately exacerbating disease progression. The BBB is critical for coordinating activity between the peripheral immune system and the brain. Importantly, BBB integrity is responsive to circulating cytokines and other immune-related signaling molecules, which are powerfully modulated by alcohol exposure. This review will highlight key cellular components of the BBB; discuss mechanisms by which permeability is achieved; offer insight into methodological approaches for assessing BBB integrity; and forecast how alcohol-induced changes in the peripheral and central immune systems might influence BBB function in individuals with a history of binge drinking and ultimately Alcohol Use Disorders (AUD).
Topics: Blood-Brain Barrier; Ethanol; Humans; Inflammation
PubMed: 34801170
DOI: 10.1016/bs.irn.2021.06.009 -
Trends in Parasitology Jul 2019Cerebral malaria is a life-threatening complication of malaria caused by the parasite Plasmodium falciparum. The growing problem of drug resistance and the dearth of new... (Review)
Review
Cerebral malaria is a life-threatening complication of malaria caused by the parasite Plasmodium falciparum. The growing problem of drug resistance and the dearth of new antiparasitic drugs are a serious threat to the antimalaria treatment regimes. Studies on humans and the murine model have implicated the disruption of the blood-brain barrier (BBB) in the lethal course of the disease. Therefore, efforts to alleviate the BBB dysfunction could serve as an adjunct therapy. Here, we review the mechanisms associated with the disruption of the BBB. In addition, we discuss the current, still limited, knowledge on the contribution of different cell types, microparticles, and the kynurenine pathway in the regulation of BBB dysfunction, and how these molecules could be used as potential new therapeutic targets.
Topics: Animals; Antimalarials; Blood-Brain Barrier; Cell-Derived Microparticles; Disease Models, Animal; Drug Development; Humans; Kynurenine; Malaria, Cerebral
PubMed: 31147271
DOI: 10.1016/j.pt.2019.04.010 -
International Journal of Molecular... Aug 2021Currently, migraine is treated mainly by targeting calcitonin gene-related peptides, although the efficacy of this method is limited and new treatment strategies are... (Review)
Review
Currently, migraine is treated mainly by targeting calcitonin gene-related peptides, although the efficacy of this method is limited and new treatment strategies are desired. Neuroinflammation has been implicated in the pathogenesis of migraine. In patients with migraine, peripheral levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α, are known to be increased. Additionally, animal models of headache have demonstrated that immunological responses associated with cytokines are involved in the pathogenesis of migraine. Furthermore, these inflammatory mediators might alter the function of tight junctions in brain vascular endothelial cells in animal models, but not in human patients. Based on clinical findings showing elevated IL-1β, and experimental findings involving IL-1β and both the peripheral trigeminal ganglion and central trigeminal vascular pathways, regulation of the Il-1β/IL-1 receptor type 1 axis might lead to new treatments for migraine. However, the integrity of the blood-brain barrier is not expected to be affected during attacks in patients with migraine.
Topics: Animals; Blood-Brain Barrier; Brain; Cell Membrane Permeability; Humans; Inflammation; Migraine Disorders
PubMed: 34445635
DOI: 10.3390/ijms22168929 -
Mechanisms of Development Nov 2015The blood-brain barrier is an evolutionary ancient structure that provides direct support and protection of the nervous system. In all systems, it establishes a tight... (Review)
Review
The blood-brain barrier is an evolutionary ancient structure that provides direct support and protection of the nervous system. In all systems, it establishes a tight diffusion barrier that hinders uncontrolled paracellular diffusion into the nervous system. In invertebrates, the blood-brain barrier separates the nervous system from the hemolymph. Thus, the barrier-forming cells need to actively import ions and nutrients into the nervous system. In addition, metabolic or environmental signals from the external world have to be transmitted across the barrier into the nervous system. The first blood-brain barrier that formed during evolution was most likely based on glial cells. Invertebrates as well as primitive vertebrates still have a purely glial-based blood-brain barrier. Here we review the development and function of the barrier forming glial cells at the example of Drosophila.
Topics: Animals; Biological Transport; Blood-Brain Barrier; Brain; Drosophila; Hemolymph; Neurons
PubMed: 26103549
DOI: 10.1016/j.mod.2015.06.002 -
Histochemistry and Cell Biology Sep 2021Progressive deterioration of the central nervous system (CNS) is commonly associated with aging. An important component of the neurovasculature is the blood-brain...
Progressive deterioration of the central nervous system (CNS) is commonly associated with aging. An important component of the neurovasculature is the blood-brain barrier (BBB), majorly made up of endothelial cells joined together by intercellular junctions. The relationship between senescence and changes in the BBB has not yet been thoroughly explored. Moreover, the lack of in vitro models for the study of the mechanisms involved in those changes impede further and more in-depth investigations in the field. For this reason, we herein present an in vitro model of the senescent BBB and an initial attempt to identify senescence-associated alterations within.
Topics: Animals; Blood-Brain Barrier; Cells, Cultured; Cellular Senescence; Endothelial Cells; Mice; Models, Biological
PubMed: 34043058
DOI: 10.1007/s00418-021-01992-z