Dexamethasone but not the equivalent doses of hydrocortisone induces neurotoxicity in neonatal rat brain

Abstract

Background:The use of dexamethasone (Dex) in premature infants to treat or prevent chronic lung disease adversely affects neurodevelopment. Recent clinical studies suggest that hydrocortisone (HC) is a safer alternative to Dex. We compared the effects of Dex and HC on neurotoxicity in newborn rats. Methods: Rat pups of a neurodevelopmental stage equivalent to premature human neonates were administered Dex or HC either as a single dose on postnatal day (PD) 6, repeated doses on PD 4 to 6 or tapering doses at PD 3 to 6 by i.p. injection. Brain weight, caspase-3 activity, and apoptotic cells were measured at PD 7; learning capability, memory, and motor function were measured at juvenile age. results: Dex decreased both body and brain weight gain, while HC did not. Tapering and repeated doses of Dex increased caspase-3 activity, cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells but HC, except at high doses, did not. Dex impaired learning and memory capability at juvenile age, while the rats exposed to HC showed normal cognitive behavior. conclusion: HC is probably safer to use than Dex in the immediate postnatal period in neonatal rats. Cautious extrapolation of these findings to human premature infants is required.

Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia

“…However, PTSD and other neuropsychiatric diseases have been linked to altered glucocorticoid signaling (Du & Pang, ; Kim et al , ). It is therefore interesting that Fmn2 expression was decreased in human neuronal progenitor cells subjected to acute or chronic dexamethasone treatment, a synthetic glucocorticoid that can have detrimental effects on neuronal function and cognitive abilities (Crochemore et al , ; Tongjaroenbuangam et al , ; Feng et al , ; Lanshakov et al , ; Fig H). We also observed decreased Fmn2 expression in post‐mortem human brain samples (hippocampus) from AD patients when compared to age‐matched control individuals (Fig I).…”

Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE)

“…This decrease in brain maturation has been found to be associated with neuronal programmed cell death, attenuated maturation, and decreased organization of synaptic connections [ 22 , 23 ]. Hydrocortisone is a better alternative to dexamethasone because at similar dosing, it lacks the adverse side effects [ 24 ]. We provide evidence that via an alternative route, through intranasal administration, hydrocortisone has a potential to be used clinically in the treatment of hypoxic-ischemic encephalopathy.…”

Endocrine disruptors also function as nervous disruptors and can be renamed endocrine and nervous disruptors (ENDs)

“… Feng et al . [ 168 ]: decreased both body and brain weight gain. Tapering and repeated doses increased caspase-3 activity.…”