Neuronal and astrocytic interactions modulate brain endothelial properties during metabolic stresses of in vitro cerebra
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RESEARCH
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Neuronal and astrocytic interactions modulate brain endothelial properties during metabolic stresses of in vitro cerebral ischemia Ganta Vijay Chaitanya1,2, Alireza Minagar3 and Jonathan S Alexander1*
Abstract Neurovascular and gliovascular interactions significantly affect endothelial phenotype. Physiologically, brain endothelium attains several of its properties by its intimate association with neurons and astrocytes. However, during cerebrovascular pathologies such as cerebral ischemia, the uncoupling of neurovascular and gliovascular units can result in several phenotypical changes in brain endothelium. The role of neurovascular and gliovascular uncoupling in modulating brain endothelial properties during cerebral ischemia is not clear. Specifically, the roles of metabolic stresses involved in cerebral ischemia, including aglycemia, hypoxia and combined aglycemia and hypoxia (oxygen glucose deprivation and re-oxygenation, OGDR) in modulating neurovascular and gliovascular interactions are not known. The complex intimate interactions in neurovascular and gliovascular units are highly difficult to recapitulate in vitro. However, in the present study, we used a 3D co-culture model of brain endothelium with neurons and astrocytes in vitro reflecting an intimate neurovascular and gliovascular interactions in vivo. While the cellular signaling interactions in neurovascular and gliovascular units in vivo are much more complex than the 3D co-culture models in vitro, we were still able to observe several important phenotypical changes in brain endothelial properties by metabolically stressed neurons and astrocytes including changes in barrier, lymphocyte adhesive properties, endothelial cell adhesion molecule expression and in vitro angiogenic potential.
Background Neurovascular and gliovascular units form the functional units in the brain [1-4]. These units consist of a highly intimate, organized and complex association between neurons, astrocytes, brain endothelium, pericytes and fibroblasts. Neurons are at the center of the neurovascular units and astrocytes are at the center of gliovascular units. In the gliovascular unit, astrocytes ensheath blood vessels at one end and at the other end communicate with neuronal pre- and post-synaptic processes [5,6]. While electrical and biochemical synapses play a key role in neuronal information exchange, astrocytes communicate through the gap junctions in their end foot processes regulated by extracellular and intracellular signaling [7,8]. Astrocytes also play a highly important role in neurovascular coupling [9-11]. These units work in a perfectly synchronized manner to regulate the * Correspondence: [email protected] 1 Department of Molecular and Cellular Physiology, Louisiana State University Health-Shreveport, Louisiana 71103, USA Full list of author information is available at the end of the article
central nervous system (CNS) biochemical and physiological processes involved in cerebral blood flow, brain energetics, blood brain barrier (BBB) pro
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