Prenatal Metyrapone Treatment Modulates Neonatal Cerebrovascular Structure, Function and Vulnerability to Mild Hypoxic-Ischemic Injury.

This study explored the hypothesis that late gestational reduction of corticosteroids transforms the cerebrovasculature, and modulates postnatal vulnerability to mild hypoxic-ischemic (HI) injury. Four groups of Sprague-Dawley neonates were studied: 1) Sham-Control; 2) Sham-MET; 3) HI-Control; 4) HI-MET. Metyrapone (MET), a corticosteroid synthesis inhibitor, was administered via drinking water from gestational day 11 to term. In Shams, MET administration: 1) decreased reactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis to surgical trauma in P9 pups by 37%; 2) promoted cerebrovascular contractile differentiation in middle cerebral arteries (MCA); 3) decreased compliance up to 46%, and increased depolarization-induced calcium mobilization n MCAs by 28%; 4) mildly increased hemispheric cerebral edema by 5%, decreased neuronal degeneration by 66% and increased astrogial and microglial activation by 10-fold and 4-fold, respectively; and 5) increased righting reflex times by 29%. Regarding HI, metyrapone-induced fetal transformation: 1) diminished reactivity of the HPA axis to HI-induced stress in P9/P10 pups; 2) enhanced HI-induced contractile de-differentiation in MCAs; 3) lessened the effects of HI on MCA compliance and calcium mobilization; 4) decreased HI-induced neuronal injury but unmasked regional HI-induced depression of microglial activation; and 5) attenuated the negative effects of HI on open field exploration, but enhanced the detrimental effects of HI on nega...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research