Influence of dexamethasone on neurotoxicity caused by oxygen and glucose deprivation in vitro.
There is conflicting evidence regarding the impact of glucocorticoid exposure on hypoxic ischemic brain injury. We examined the effects of timing, duration, and concentration of dexamethasone on neuronal injury following in vitro oxygen glucose deprivation (OGD). Dissociated embryonic rat basal forebrain cells were cultured and either preincubated with dexamethasone for 72 h or continuously exposed prior to, during, and after OGD. Injury was assessed by morphology rating and cholineacetyltransferase (ChAT) activity at Day 13 in vitro, 2 days after OGD. Preincubation with nanomolar concentrations of dexamethasone resulted in a dose-dependent exaggeration of injury. Combined glutamate receptor antagonist application negated this deleterious effect, suggesting that dexamethasone may increase glutamate release, decrease uptake, or upregulate glutamate receptor expression. Continuous application of a narrow concentration range of dexamethasone (100 nM and 1 microM) prior to, during, and after insult protected neurons. Dose, timing, and duration of glucocorticoid administration may each be critical variables influencing outcome of hypoxic ischemic brain insult.
Flavin
M P
MP
Department of Pediatrics, Queen's University, Kingston, Ontario, Canada.
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005947:Glucose / Q000172:deficiency*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009422:Nervous System Diseases / Q000139:chemically induced; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D002795:Choline O-Acetyltransferase; D005947:Glucose