The effects of 17beta-estradiol on ischemia-induced neuronal damage in the gerbil hippocampus.
The effects of 17beta-estradiol, a potent estrogen, on ischemia-induced neuronal damage, membrane depolarization and changes in intracellular Ca2+ concentration were studied in gerbil hippocampi. The histological outcome evaluated seven days after 3 min of transient forebrain ischemia in hippocampal CA1 pyramidal cells was improved by high doses of 17beta-estradiol (30 microg, i.c.v. and 4 mg/kg, i.p.), whereas low doses of 17beta-estradiol (3 and 10 microg, i.c.v.) showed no protective effect. Administration of 17beta-estradiol did not affect the changes in the direct current potential shift in ischemia in the hippocampal CA1 area at any dosage. A hypoxia-induced intracellular Ca2+ increase was evaluated by in vitro microfluorometry in gerbil hippocampal slices. Pretreatment of 17beta-estradiol (4 mg/kg, injected i.p. 1 h before decapitation) suppressed the increase in the intracellular concentration of Ca2+ due to the in vitro hypoxia, affecting both the onset of the increase and the extent. The in vitro hypoxia in the Ca2+-free condition induced an elevation of the intracellular concentration of Ca2+, although the increase was gradual. Pretreatment of 17beta-estradiol (4 mg/kg, i.p.) also inhibited this elevation. These findings imply that high doses of 17beta-estradiol protect the neurons from ischemia by inhibiting the release of Ca2+ from the intracellular Ca2+ stores, as well as by inhibiting the influx of Ca2+ from the extracellular space.
Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Japan.
J
J
Chen
N
N
Adachi
K
K
Liu
T
T
Arai
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001925:Brain Damage, Chronic / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects; D004958:Estradiol / Q000627:therapeutic use*; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*
D015220:Calcium Channels; D018696:Neuroprotective Agents; D004958:Estradiol; D002118:Calcium