title: Preconditioning by oxygen-glucose deprivation preserves cell proliferation and reduces cytotoxicity in primary astrocyte cultures.
abstract: Hypoxic-ischemic preconditioning (HIPC) has a neuroprotective effect against a subsequent, more severe perinatal hypoxic-ischemic episode. The protective processes of preconditioning (PC) in the immature brain remain undefined but are most likely related to the immune cells of the central nervous system. To determine the role of astrocytes in HIPC, we initially exposed primary rat astrocytes to oxygen-glucose deprivation (OGD) for 30 minutes as a PC stimulus. A subsequent more severe insult was induced 24 hours later by exposing the astrocytes to OGD for 3 hours. These experiments revealed that OGD for 3 hours induced increased cytotoxicity as measured by lactate dehydrogenase in primary astrocytes, which was diminished in astrocytes earlier subjected to PC. Moreover, decreased cell proliferation, as measured by Ki67, and lower cytokine expression (IL-1β, TNF-α, IL-6, IL-10) were observed in astrocytes subjected to OGD for 3 hours, while these levels remained unchanged in PC+OGD cells. Therefore, we speculate that PC by OGD may affect the survival, proliferation and function of primary cultured astrocytes which may partly explain the neuroprotective properties of HIPC seen in HI rat models.
authors.affiliation: Department of Neuropsychology - Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht 6200MD, The Netherlands. m.nikiforou@maastrichtuniversity.nl.
authors.forename: Maria
authors.initials: M
authors.lastname: Nikiforou
authors.forename: Evi
authors.initials: E
authors.lastname: Vlassaks
authors.forename: Eveline
authors.initials: E
authors.lastname: Strackx
authors.forename: Boris
authors.initials: B
authors.lastname: W Kramer
authors.forename: Johan S H
authors.initials: JS
authors.lastname: Vles
authors.forename: Antonio W D
authors.initials: AW
authors.lastname: Gavilanes
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology*; D039481:CD11b Antigen / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D019194:Ischemic Preconditioning / Q000379:methods*; D019394:Ki-67 Antigen / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D007770:L-Lactate Dehydrogenase; D005947:Glucose