title: Glucocorticoid Induced Cerebellar Toxicity in the Developing Neonate: Implications for Glucocorticoid Therapy during Bronchopulmonary Dysplasia.
abstract: Prematurely born infants commonly suffer respiratory dysfunction due to the immature state of their lungs. As a result, clinicians often administer glucocorticoid (GC) therapy to accelerate lung maturation and reduce inflammation. Unfortunately, several studies have found GC therapy can also produce neuromotor/cognitive deficits and selectively stunt the cerebellum. However, despite its continued use, relatively little is known about how exposure to this hormone might produce neurodevelopmental deficits. In this review, we use rodent and human research to provide evidence that GC therapy may disrupt cerebellar development through the rapid induction of apoptosis in the cerebellar external granule layer (EGL). The EGL is a transient proliferative region responsible for the production of over 90% of the neurons in the cerebellum. During normal development, endogenous GC stimulation is thought to selectively signal the elimination of the EGL once production of new neurons is complete. As a result, GC therapy may precociously eliminate the EGL before it can produce enough neurons for normal cerebellar function. It is hoped that this review may provide information for future clinical research in addition to translational guidance for the safer use of GC therapy.
authors: Department of Psychiatry, School of Medicine, Washington University in St. Louis, 660 South Euclid, Box #8134, St. Louis, MO 63110, USA; Tel.: +1-314-362-7007;
authors: Kevin K
authors: KK
authors: Noguchi
keywords: 11β-Hydroxysteroid Dehydrogenase Type II; apoptosis; betamethasone; bronchopulmonary dysplasia; cerebellum; dexamethasone; external granule layer; hydrocortisone; neural progenitor cell