Effects of DHEA and DHEAS in Neonatal Hypoxic-Ischemic Brain Injury

Neonatal brain injury remains a significant issue with limited treatment options. The endogenous neurosteroids dehydroxyepiandrosterone (DHEA) and its sulfate ester (DHEAS) have demonstrated promising therapeutic potential in adult brain injury models due to their neuroprotective mechanisms. This study aimed to analyze the neuroprotective potential of DHEA and DHEAS with a particular interest in anti-oxidative properties in a mouse model of neonatal hypoxic-ischemic brain injury. Using the modified Rice-Vanucci model, brain injury was induced in 7-day-old mouse pups, followed by treatment with various concentrations of DHEA and DHEAS (0.1, 1, and 10 µg/g body weight) via intraperitoneal injection after a 2-hour recovery period. Mice were sacrificed after 24 hours for analysis of somatometry, brain injury, apoptosis, microglial activation, and oxidative stress markers (NOX2, 4-HNE, 8-OHdG), along with the anti-oxidant marker SOD1. No statistically significant effects of the treatments were observed at the tested doses and time points. Although this study did not conclusively demonstrate the anti-oxidative neuroprotective potential of DHEA or DHEAS, neither substance exhibited toxic or harmful effects. Several factors may have contributed to the lack of observable effects, underscoring the need for further refinement in future studies of DHEA(S) and other treatments of neonatal hypoxic-ischemic brain injury.