Prenatal Dexamethasone Exposure Causes Loss of Neonatal Hypoxia Tolerance: Cellular Mechanisms

Abstract

~~~[~iirlll!t~tll (~/ ' / ' / 1 ( 1 r t~7~i~~o I o~y j~, Diikc Lrtiivor.\i/!, .\lc,dii~11 C'cti~cr, Di/r/i(~tl~, ~\'or~/i C7(iroliti (i 27710 ABSTRACT. Glucocorticoids promote lung cell differen-for surfactant synthesis. This beneficial effect has led to widetiation and thus enhance surfactant synthesis in the man-spread use of glucocorticoids by obstetricians and pediatricians agement of neonatal respiratory distress syndrome. Be-to prevent or treat neonatal respiratory distress syndrome in cause they also accelerate differentiation in other targets, infants born prematurely. However, enhanced cell difTcrentiation glucocorticoids may compromise physiologic responses comes at the expense of cell proliferation (1). leading to shortfalls that operate through specialized fetal-neonatal mecha-in lung cell number, especially at the high doses typical of clinical nisms. The current study csplores one such process, the steroid use (2). The compound effects of glucocorticoid exposure capacity to maintain cardiac function during hyposia, a during development, sacrificing cell division in favor of differcritical function in light of the hyposia associated with entiation. are also seen in systems other than the intended parturition and with neonatal respiratory distress. Preg-therapeutic target: in the nervous system, general impairment of nant rats were given 0.05, 0.2, or 0.8 mg/kg of desameth-cell acquisition is paired with selective promotion of developasone on gestational d 17, 18, and 19, and the response to ment of a number of neurotransmitter systems, most notably hyposia was assessed in the offspring on the day after catecholaminergic pathways (3-6). In the liver, targeting of catebirth. Desamethasonc produced a dose-dependent impair-cholamine ncurotr~nsmission leads to a premature transition ment of survival during esposure to 5% 01 (5 kPa 0 2 ) for from fetal ij-receptor-mediated control of glucose metabolism to 120 min. ECG measurements showed that death in the the adult mechanism dominated by tul-receptors (7). Unlike the desamethasone-exposed animals was preceded by multiple situation in the lung. where an accelerated time course of cell arrhythmias and progressive atrioventricular conduction differentiation is beneficial in treating respiratory distress syndefects, terminating in cardiac arrest. Because maintenance drome, the promotional effect on hepatic adrcnergic mechanisms of neonatal cardiac conduction during hyposia depends on is detrimental. ij-Adrenergic dominance in the fetal-neonatal adrenergic mechanisms operating through adrenomedul-period is adaptive for the carbohydrate-poor milk diet that relary catecholamine release and actions at transiently cs-quires gluconeogenesis: this metabolic process is effectively pressed a*-receptors in the immature myocardium, we linked to @-receptors, with the appropriate stimulus supplied by examined these mechanisms in control and desametha-a ij-adrcnergic agonist (epinephrine) released from the adrenal sone-esposed neonates. Desamethasone caused cardiac a*-m...

Long-Term Prenatal Hypoxia Alters Maturation of Adrenal Medulla in Rat

“…These data indicate that prenatal Hx disturbs the ontogenesis of adrenal function by altering processes involved in the synthesis or release of NE and E. The major effects in this respect were exhibited during the perinatal period, but this impairment persisted into adulthood. Similarly, altered adrenomedullary development has been previously reported in connection with intrauterine growth retardation (46), prenatal exposure to dexamethasone (47), and placental restriction (48). All these previous findings together with our results indicate that insult during gestation impaired adrenal function.…”

Neuroprotective effect of magnesium sulfate and dexamethasone on intrauterine ischemia in the fetal rat brain: ultrastructural evaluation

“…In our work, dexamethasone decreased the TBARS values back to control levels and decreased the mitochondrial damage when compared to ischemic brain injury group. The neuroprotective effect of dexamethasone is well correlated with previous studies (4,5,13,15). When compared to each other magnesium sulphate and dexamethasone had no statistical difference in their effects on TBARS values or mitochondrial scores suggesting that both drugs were equally neuroprotective in our study.…”

“…The dexamethasone exerts a series of effects on injured neural tissue (13,20). These effects are the regulation of energy metabolism, the prevention of progressive posttraumatic ischemia, the prevention of neurofilament degradation and the inhibition of membrane lipid hydrolysis (3,4,25).…”

Postnatal steroid treatment and brain development

“…N decreased survival after prenatal dexamethasone treatment among 1 day old rats breathing 5% O 2 43 N exacerbation of neuronal and astroglial injury induced by hypoxia or hypoglycaemia in fetal rat hippocampal cell cultures exposed to corticosterone 44 N decrease in the number of surviving motor neurones after nerve transaction 45 N increased ischaemic brain damage after carotid artery occlusion 46 In contrast, protective effects have been also reported:…”