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      Astrocytic modulation of blood brain barrier: perspectives on Parkinson’s disease

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          Abstract

          The blood–brain barrier (BBB) is a tightly regulated interface in the Central Nervous System (CNS) that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells (ECs), pericytes and astrocytes that create a neurovascular unit (NVU) with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Under neurological disorders, such as chronic cerebral ischemia, brain trauma, Epilepsy, Alzheimer and Parkinson’s Diseases, a disruption of the BBB takes place, involving a lost in the permeability of the barrier and phenotypical changes in both the ECs and astrocytes. In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival. In this review we discuss the implications of astrocyte functions in the protection of the BBB, and in the development of Parkinson’s disease (PD) and related disorders. Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.

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          Most cited references113

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          Endothelial cell-cell junctions: happy together.

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            Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs.

            We have generated mice homozygous for a disruption of the mdr1a (also called mdr3) gene, encoding a drug-transporting P-glycoprotein. The mice were viable and fertile and appeared phenotypically normal, but they displayed an increased sensitivity to the centrally neurotoxic pesticide ivermectin (100-fold) and to the carcinostatic drug vinblastine (3-fold). By comparison of mdr1a (+/+) and (-/-) mice, we found that the mdr1a P-glycoprotein is the major P-glycoprotein in the blood-brain barrier and that its absence results in elevated drug levels in many tissues (especially in brain) and in decreased drug elimination. Our findings explain some of the side effects in patients treated with a combination of carcinostatics and P-glycoprotein inhibitors and indicate that these inhibitors might be useful in selectively enhancing the access of a range of drugs to the brain.
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              The blood-brain barrier in health and disease.

              The blood-brain barrier (BBB) is a term used to describe a series of properties possessed by the vasculature of the central nervous system (CNS) that tightly regulate the movement of ions, molecules, and cells between the blood and the CNS. This barrier is crucial to provide the appropriate environment to allow for proper neural function, as well as protect the CNS from injury and disease. In this review, I discuss the cellular and molecular composition of the BBB and how the development and function of the BBB is regulated by interactions with the CNS microenvironment. I further discuss what is known about BBB dysfunction during CNS injury and disease, as well as methodology used to deliver drugs across the BBB to the CNS. Copyright © 2012 American Neurological Association.

                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                17 June 2014
                04 August 2014
                2014
                : 8
                : 211
                Affiliations
                [1] 1Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana Bogotá, D.C., Colombia
                [2] 2Departamento de Biofunção, Universidade Federal da Bahia Salvador, Brazil
                [3] 3Instituto Cajal, CSIC Madrid, Spain
                [4] 4Laboratorio de Citoarquitectura y Plasticidad Neuronal, Facultad de Medicina, Instituto de Investigaciones cardiológicas Prof. Dr. Alberto C. Taquini (ININCA), UBA-CONICET, Buenos Aires Argentina
                [5] 5Cellular and Molecular Neurobiology Area, Group of Neuroscience of Antioquia, Faculty of Medicine, SIU, University of Antioquia UdeA Medellín, Colombia
                Author notes

                Edited by: Rubem C. A. Guedes, Universidade Federal de Pernambuco, Brazil

                Reviewed by: Hajime Hirase, RIKEN - Brain Science Institute, Japan; Ping Liu, University of Connecticut Health Center, USA

                *Correspondence: George E. Barreto, Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Edf. Carlos Ortiz, Oficina 107, Cra 7 40-62, Bogotá, D.C., Colombia e-mail: gsampaio@ 123456javeriana.edu.co

                This article was submitted to the journal Frontiers in Cellular Neuroscience.

                Article
                10.3389/fncel.2014.00211
                4120694
                25136294
                7cfeacac-470f-4e37-884f-d4c25a42baff
                Copyright © 2014 Cabezas, Ávila, Gonzalez, El-Bachá, Báez, Garcia-Segura, Jurado Coronel, Capani, Cardona-Gomez and Barreto.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 May 2014
                : 14 July 2014
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 143, Pages: 11, Words: 10091
                Categories
                Neuroscience
                Review Article

                Neurosciences
                bbb,astrocytes,reactive astrogliosis,endothelial cells,parkinson disease
                Neurosciences
                bbb, astrocytes, reactive astrogliosis, endothelial cells, parkinson disease

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