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      The cerebral circulation and cerebrovascular disease I: Anatomy.

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          Abstract

          In this paper, which is the first in a three-part series that reviews cerebrovascular anatomy, pathogenesis, and stroke, we lay the anatomical foundation for the rest of the series. Beginning with its origin in the branches of the aorta, we start by describing the arterial system. This system is partitioned into two major divisions (anterior and posterior circulations) that differ significantly in features and pathogenic potential. The systems, and the major branches that comprise them, are described. Description of the arterial system proceeds to the point of the fulfillment of its function. This function, the exchange of gases and nutrients with the cerebral parenchyma, is the subject of a subsequent section on the microcirculation and blood-brain barrier. Finally, the cerebral venous system, which is composed of cerebral veins and dural venous sinuses, is described. Thus, an anatomical context is supplied for the discussion of cerebrovascular disease pathogenesis provided by our second paper.

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          Most cited references80

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          The blood-brain barrier: an engineering perspective

          It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlich's first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and this selective permeability remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore, advances in our understanding of the structure and function of the blood-brain barrier are key to developing effective treatments for a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases.
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            Pericytes in the microvasculature.

            Pericytes, also known as Rouget cells or mural cells, are associated abluminally with all vascular capillaries and post-capillary venules. Differences in pericyte morphology and distribution among vascular beds suggest tissue-specific functions. Based on their location and their complement of muscle cytoskeletal proteins, pericytes have been proposed to play a role in the regulation of blood flow. In vitro studies demonstrating the contractile ability of pericytes support this concept. Pericytes have also been suggested to be oligopotential and have been reported to differentiate into adipocytes, osteoblasts and phagocytes. The mechanisms involved in vessel formation have yet to be elucidated but observations indicate that the primordial endothelium can recruit undifferentiated mesenchymal cells and direct their differentiation into pericytes in microvessels, and smooth muscle cells in large vessels. Communication between endothelial cells and pericytes, or their precursors, may take many forms. Soluble factors such as platelet-derived growth factor and transforming growth factors-beta are likely to be involved. In addition, physical contact mediated by cell adhesion molecules, integrins and gap junctions appear to contribute to the control of vascular growth and function. Development of culture methods has allowed some functions of pericytes to be directly examined. Co-culture of pericytes with endothelial cells leads to the activation of transforming growth factor-beta, which in turn influences the growth and differentiation of the vascular cells. Finally, the pericyte has been implicated in the development of a variety of pathologies including hypertension, multiple sclerosis, diabetic microangiopathy and tumor vascularization.
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              Blood-brain barrier drug targeting: the future of brain drug development.

              As human longevity increases, the likelihood of the onset of diseases of the brain (and other organs) also increases. Clinical therapeutics offer useful long-term treatments, if not cures, if drugs can be delivered appropriately and effectively. Unfortunately, research in drug transport to the brain has not advanced very far. Through better characterization of the transport systems utilized within the blood-brain barrier, a greater understanding of how to exploit these systems will lead to effective treatments for brain disorders. Pardridge reviews the functions of the various known transport systems in the brain and discusses how the development of BBB drug-targeting programs in pharmaceutical and academic settings may lead to more efficacious treatments.
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                Author and article information

                Journal
                Brain Circ
                Brain circulation
                Medknow
                2455-4626
                2394-8108
                April 1 2017
                : 3
                : 2
                Affiliations
                [1 ] Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, MI, USA.
                [2 ] Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
                Article
                BC-3-45
                10.4103/bc.bc_10_17
                6126264
                30276305
                71936708-f4fd-4827-a0b3-4f5a611ae218
                History

                Cerebral arteries,blood brain barrier,cerebral circulation,cerebral microcirculation,cerebral venous system,cerebrovascular anatomy,cerebrovascular disease

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