Metyrapone reduces rat brain damage and seizures after hypoxia-ischemia: an effect independent of modulation of plasma corticosterone levels?
Hypoxia-ischemia is accompanied by abundant corticosterone secretion that could exacerbate brain damage after the insult. The authors demonstrate that the steroid synthesis inhibitor metyrapone (150 mg/kg subcutaneously) suppresses the hypoxia-ischemia-induced rise of plasma corticosterone levels (17.3 +/- 3.6 micrograms/dL) when compared with corticosterone-treated animals (72.2 +/- 4.8 micrograms/dL) immediately after hypoxia-ischemia. In parallel, metyrapone reduced brain damage (P < 0.05). Moreover, none of the metyrapone-treated animals displayed seizures, whereas seven of eight corticosterone-treated animals had seizures after hypoxia-ischemia. Although corticosterone administration in metyrapone-treated animals elevated plasma corticosterone levels (39.0 +/- 5.3 micrograms/dL), this did not result in a subsequent increase in brain damage and seizures when compared with metyrapone-treated animals. The authors conclude that metyrapone reduces brain damage and the incidence of seizures after hypoxia-ischemia but that this effect might partially be independent from its effect on modulating plasma corticosterone levels.
Krugers
H J
HJ
Department of Biological Psychiatry, University of Groningen, The Netherlands.
Kemper
R H
RH
Korf
J
J
Ter Horst
G J
GJ
Knollema
S
S
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001831:Body Temperature; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003345:Corticosterone / Q000097:blood*; D004827:Epilepsy / Q000209:etiology / Q000517:prevention & control*; D002534:Hypoxia, Brain / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008124:Locomotion; D008297:Male; D008797:Metyrapone / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D018696:Neuroprotective Agents; D003345:Corticosterone; D008797:Metyrapone