Metyrapone reduces rat brain damage and seizures after hypoxia-ischemia: an effect independent of modulation of plasma corticosterone levels?

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
H J KrugersS Knollema

Abstract

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.

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Citations

Mar 6, 1999·Neurosurgical Review·C A KochG P Chrousos
Sep 20, 2011·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Ehsan SabooryShiva Roshan-Milani
Mar 6, 2012·European Journal of Pharmacology·Jean-Baptiste DrouetFrédéric Canini
Aug 5, 2011·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Omer AtesSaime Sezer
May 13, 2017·Neuropharmacology·Luis García-GarcíaMiguel A Pozo
Oct 26, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·H J KrugersM Joëls
Feb 3, 2005·British Medical Bulletin·Daqing MaMervyn Maze
Oct 28, 2008·Stress : the International Journal on the Biology of Stress·Thomas A HarrisBarbara E Lingwood
Feb 28, 2008·Stress : the International Journal on the Biology of Stress·C D ConradR J Hobbs
Dec 7, 2019·Progress in Neuro-psychopharmacology & Biological Psychiatry·Rafael Pazinatto AguiarRúbia M Weffort Oliveira

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