TY - JOUR
T1 - Preconditioning by Oxygen-Glucose Deprivation Preserves Cell Proliferation and Reduces Cytotoxicity in Primary Astrocyte Cultures
AU - Nikiforou, Maria
AU - Vlassaks, Evi
AU - Strackx, Eveline
AU - Kramer, Boris W.
AU - Vles, Johan S. H.
AU - Gavilanes, Antonio W. D.
PY - 2015
Y1 - 2015
N2 - 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-1 beta, TNF-alpha, 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.
AB - 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-1 beta, TNF-alpha, 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.
KW - Astrocytes
KW - cytokines
KW - hypoxia-ischemia
KW - hypoxic-ischemic preconditioning
KW - oxygen-glucose deprivation
KW - proliferation
U2 - 10.2174/1871527314666150116120518
DO - 10.2174/1871527314666150116120518
M3 - Article
C2 - 25613497
SN - 1871-5273
VL - 14
SP - 61
EP - 67
JO - Cns & Neurological Disorders-Drug Targets
JF - Cns & Neurological Disorders-Drug Targets
IS - 1
ER -