Oxytocin is neuroprotective against oxygen-glucose deprivation and reoxygenation in immature hippocampal cultures.
Oxytocin triggers an excitatory-to-inhibitory switch in GABA (gamma-aminobutyric acid) actions in immature neurons and this was found to increase their resistance to anoxic episodes. In this study we examined the neuroprotective effect of oxytocin on immature hippocampal cultures subjected to oxygen-glucose deprivation (OGD) both immediately after the insult, as well as after 6h of reoxygenation. We measured metabolic activity fluorometrically using resazurin and found that cellular viability was increased in the oxytocin treated group both immediately after OGD, as well as after 6 h of reoxygenation. While the oxytocin receptor antagonist atosiban blocked the effect of oxytocin, the Na+-K+-2Cl(-) cotransporter (NKCC1) blocker bumetanide protected neurons after reoxygenation. The effects of oxytocin are dose-related. Our results suggest that oxytocin exerts a prolonged neuroprotective action on fetal neurons. Perinatal pharmacologic manipulation of oxytocin receptors may have detrimental effects by increasing susceptibility of the fetal brain to hypoxic-ischemic insults.
Ceanga
Mihai
M
Department of Physiology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania.
Spataru
Ana
A
Zagrean
Ana-Maria
AM
D000818:Animals; D000831:Animals, Newborn; D002034:Bumetanide / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010121:Oxytocin / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D028021:Sodium-Potassium-Chloride Symporters / Q000502:physiology; D064506:Solute Carrier Family 12, Member 2; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
D018045:Receptors, Oxytocin; C578879:Slc12a2 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; C047046:atosiban; D002034:Bumetanide; D010121:Oxytocin; D005947:Glucose; D010100:Oxygen; D014668:Vasotocin