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      Glial Connexins and Pannexins in the Healthy and Diseased Brain

      1 , 1 , 1 , 1
      Physiological Reviews
      American Physiological Society

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          Abstract

          Over the past several decades a large amount of data have established that glial cells, the main cell population in the brain, dynamically interact with neurons and thus impact their activity and survival. One typical feature of glia is their marked expression of several connexins, the membrane proteins forming intercellular gap junction channels and hemichannels. Pannexins, which have a tetraspan membrane topology as connexins, are also detected in glial cells. Here, we review the evidence that connexin and pannexin channels are actively involved in dynamic and metabolic neuroglial interactions in physiological as well as in pathological situations. These features of neuroglial interactions open the way to identify novel non-neuronal aspects that allow for a better understanding of behavior and information processing performed by neurons. This will also complement the “neurocentric” view by facilitating the development of glia-targeted therapeutic strategies in brain disease.

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          Tumour exosome integrins determine organotropic metastasis

          Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
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            Astrocyte-endothelial interactions at the blood-brain barrier.

            The blood-brain barrier, which is formed by the endothelial cells that line cerebral microvessels, has an important role in maintaining a precisely regulated microenvironment for reliable neuronal signalling. At present, there is great interest in the association of brain microvessels, astrocytes and neurons to form functional 'neurovascular units', and recent studies have highlighted the importance of brain endothelial cells in this modular organization. Here, we explore specific interactions between the brain endothelium, astrocytes and neurons that may regulate blood-brain barrier function. An understanding of how these interactions are disturbed in pathological conditions could lead to the development of new protective and restorative therapies.
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              An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

              Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term "stroke" is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.
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                Author and article information

                Contributors
                Journal
                Physiological Reviews
                Physiological Reviews
                American Physiological Society
                0031-9333
                1522-1210
                January 01 2021
                January 01 2021
                : 101
                : 1
                : 93-145
                Affiliations
                [1 ]Collège de France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, Paris, France; University Pierre et Marie Curie, Paris, France; MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, Paris, France; Department of Cellular & Physiological Sciences, Life Sciences Institute, Faculty of Medicine, University of British Columbia,...
                Article
                10.1152/physrev.00043.2018
                32326824
                7f419d0c-fd73-4da4-a60d-e48b8708dfc2
                © 2021
                History

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