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      The gut microbiota influences blood-brain barrier permeability in mice.

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          Abstract

          Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to regulate barrier function in endothelial tissues. Exposure of germ-free adult mice to a pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. Our results suggest that gut microbiota-BBB communication is initiated during gestation and propagated throughout life.

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          Most cited references21

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          Critical period regulation.

          Neuronal circuits are shaped by experience during critical periods of early postnatal life. The ability to control the timing, duration, and closure of these heightened levels of brain plasticity has recently become experimentally accessible, especially in the developing visual system. This review summarizes our current understanding of known critical periods across several systems and species. It delineates a number of emerging principles: functional competition between inputs, role for electrical activity, structural consolidation, regulation by experience (not simply age), special role for inhibition in the CNS, potent influence of attention and motivation, unique timing and duration, as well as use of distinct molecular mechanisms across brain regions and the potential for reactivation in adulthood. A deeper understanding of critical periods will open new avenues to "nurture the brain"-from international efforts to link brain science and education to improving recovery from injury and devising new strategies for therapy and lifelong learning.
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            The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications.

            Human pathologies such as vascular malformations, hemorrhagic stroke, and edema have been associated with defects in the organization of endothelial cell junctions. Understanding the molecular basis of these diseases requires different integrated approaches which include basic cell biology, clinical studies, and studies in animal models such as mice and zebrafish. In this review we discuss recent findings derived from these approaches and their possible integration in a common picture.
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              The microbiology of butyrate formation in the human colon

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                Author and article information

                Journal
                Sci Transl Med
                Science translational medicine
                1946-6242
                1946-6234
                Nov 19 2014
                : 6
                : 263
                Affiliations
                [1 ] Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden. viorica.braniste@ki.se sven.pettersson@ki.se.
                [2 ] Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
                [3 ] Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA.
                [4 ] Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, 17176 Stockholm, Sweden.
                [5 ] Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
                [6 ] Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
                [7 ] Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, 17176 Stockholm, Sweden. Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
                [8 ] Department of Laboratory Medicine, Karolinska Institutet, 14186 Stockholm, Sweden.
                [9 ] Department of Biosciences and Nutrition, Karolinska Institutet, and School of Technology and Health, KTH Royal Institute of Technology, Novum, SE-141 57 Huddinge, Sweden.
                [10 ] Laboratory of Functional Neuroanatomy, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA.
                [11 ] Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden. Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 637551, Singapore. viorica.braniste@ki.se sven.pettersson@ki.se.
                Article
                6/263/263ra158 NIHMS677533
                10.1126/scitranslmed.3009759
                25411471
                2d0a6303-5043-43c7-aad6-1da68f76d00e
                Copyright © 2014, American Association for the Advancement of Science.

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