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Title: Rat Astrocytes and Brain Pericytes: Secretome Profiles of Cytokines and Chemokines During Anoxia
Authors: Zeinab Adel Mahmoud Samy Sayed 
Supervisor: Prof. Zoran Redzic
Keywords: Astrocytes : brain
Issue Date: 2017
Publisher:  Kuwait university - college of graduate studies
Abstract: Cerebral ischemia occurs when cerebral blood flow is reduced to a point at which it is not sufficient to sustain local metabolism, which causes functional impairment and could lead to brain tissue damage. Protective or detrimental effects of several cytokines and chemokines that are released from the cells of the neurovascular unit during cerebral ischemia are well documented. However, no study so far has explored the secretome profile of a large panel of these signalling molecules. The aim of this in vitro study was to use advantages of a recently developed multi-array assay in order to explore time patterns of secretion of 30 cytokines and chemokines from rat brain astrocytes and pericytes in primary cultures during anoxia and to compare these to the corresponding pattern of secretion in the presence of oxygen. Primary cultures were produced and exposed either to normoxia or anoxia for 2-48h. After exposure, the conditioned medium was harvested and processed for profiling of cytokines and chemokines using a rat cytokine array panel. In addition, the time pattern of angiopoietin-1 secretion was determined by ELISA. Changes in secretion of cytokines and chemokines from astrocytes during anoxia were related to a particular molecular network by importing the data into the Core Analysis tool of Ingenuity Pathways Analysis (IPA) software. The main findings were that astrocytes secreted all tested cytokines at various time points even in the presence of oxygen. During anoxia, secretion of these cytokines has largely increased, though different time patterns were revealed for different cytokines. In contrast to astrocytes, pericytes released 20-26 cytokines in the presence of oxygen, while in anoxia this secretion was severely reduced. A striking observation was that concentrations of most cytokines were higher in the medium harvested from pericytes (regardless of the conditions) than in the medium harvested from astrocytes. IPA analysis revealed that the main pathway that was triggered in astrocytes by anoxia was HIF-1α mediated pathway. However, three other pathways that are related to antigen presentation and inflammation were also triggered in astrocytes. Thus, it appears that astrocytes play an important role in triggering and regulating inflammation in cerebral hypoxia/ ischemia.
Appears in Programs:0530 Physiology (M.Sc.)

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