ArtPoster
TitelEffect of the neuroactive steroids DHEA and DHEA-S on microglial cell activation in a mouse model of neonatal hypoxic-ischemic brain injury
TopicNeonatologie
Einleitung

Despite the progress in medical care of preterm infants and sick newborns, prematurity and perinatal asphyxia are still associated with a high risk of neonatal cerebral damage. Causal therapies are currently lacking. The neuroactive steroids dehydroepiandrosterone (DHEA) and its sulfate ester DHEA-S are a promising option to reduce microglial cell activation in the wake of perinatal brain injury.

Patient/en und Methoden

In this experimental study we assessed microglial cell activation in 87 neonatal mouse brains, which were either healthy or injured by hypoxia-ischemia. In a first step, conducted as a toxicity study, 39 healthy mice were randomly assigned to one of eight treatment groups and received an intraperitoneal injection of either phosphate-buffered saline (PBS), PBS+ dimethyl sulfoxide (DMSO, -“solvent control”) or DHEA or DHEA-S in different concentrations. In a second step, 48 animals were subjected to hypoxic-ischemic brain injury by ligation of the right common carotid artery and subsequent exposure to a hypoxic environment. Study animals were then randomly assigned to the above-mentioned treatment groups (n=6), stratified by gender (1:1). All brains were histologically processed and coronal brain sections were immunohistochemically stained with microglial specific Anti IBA-1 to determine the number of activated microglial cells in different brain regions.

Ergebnisse

At this point the analysis of the toxicity study is still ongoing.
In the hypoxic-ischemic injury study, no significant differences in microglial cell activation were detected between the different treatment groups. There were significant differences in the number of activated microglial cells between male and female mice in three different brain regions of the right hemisphere, namely the thalamus (PBS, p=0.048), hippocampal formation (PBS/DMSO, p=0.02) and at white matter (DHEA 10µg/g bodyweight, p=0.007).

Schlussfolgerung/Diskussion

The study did not reveal an effect of DHEA or DHEAS on microglial cell activation in the hypoxic ischemic injured mouse brain. There are some limitations, such as the small number of cases or the manual microscopic analysis, which might affect the number of detected activated cells. The relevance of the observed sex difference is uncertain, as only some regions without a distinct pattern were affected and the number of cases is low, but further investigation is ongoing.

review
Erstautor*in ist unter 35 Jahre alt
Autor*in 1Sandra Bergerweiß Department of Pediatrics II, Medical University of Innsbruck, Innsbruck, Austria
Autor*in 2Julia Saurer Department of Pediatrics II, Medical University of Innsbruck, Innsbruck, Austria
Autor*in 3Martina Urbanek Department of Pediatrics II, Medical University of Innsbruck, Innsbruck, Austria
Autor*in 4Eva Huber Department of Pediatrics II, Medical University of Innsbruck, Innsbruck, Austria
Autor*in 5Ursula Kiechl-Kohlendorfer Department of Pediatrics II, Medical University of Innsbruck, Innsbruck, Austria
Autor*in 6Elke Griesmaier Department of Pediatrics II, Medical University of Innsbruck, Innsbruck, Austria
Autor*in 7Anna Posod Department of Pediatrics II, Medical University of Innsbruck, Innsbruck, Austria