ArtPoster
TitelThe effect of DHEA and DHEA-S on activated-caspase-3 apoptotic cell death in the healthy and injured neonatal mouse brain
TopicNeonatologie
Einleitung

Neonatal hypoxic-ischemic encephalopathy (HIE), a consequence of perinatal asphyxia, still poses a therapeutic challenge for neonatologists. A promising treatment option are the hormone dehydroepiandrosterone (DHEA) and its sulfate ester DHEA-S, due to their neuroprotective properties. This work evaluates a potential protective effect of DHEA and DHEA-S in neonatal mouse pups suffering from hypoxic-ischemic brain injury.

Patient/en und Methoden

This experimental study examined activated caspase-3-dependent apoptosis in the brain of 87 mouse pups. In a first step, a toxicity study in healthy animals was conducted. Thirty-nine mouse pups were randomly assigned to one of the following treatment groups. Every individual received a single intraperitoneal injection of either PBS (phosphate-buffered saline, control), PBS/DMSO (dimethyl sulfoxide, “solute control”), different concentrations of DHEA (0.1 µg, 1 µg or 10 µg per g bodyweight), or different concentrations of DHEA-S (0.1 µg, 1 µg or 10 µg per g bodyweight). In a second step, 48 animals were subjected to hypoxic-ischemic brain injury. Therefore, the right common carotid artery was ligated and cut, and the study animals were placed in a hypoxic chamber filled with 8% oxygen and 92% nitrogen for 17 minutes. Subsequently, they were randomly assigned to the above-mentioned treatment groups. Mouse brains were histologically processed and immunohistochemically stained. Coronal brain sections were assessed via light microscopy and caspase-3 positive cells quantified in various brain regions (grey matter, white matter, hippocampus, striatum, thalamus, hypothalamus).

Ergebnisse

In the toxicity study, significantly lower numbers of activated caspase-3-positive cells were found in animals treated with DHEA 10 µg/g bodyweight in grey matter (p=0.036, vs. PBS). No other statistically significant difference was detected. In animals subjected to hypoxic-ischemic brain injury, DHEA and DHEA-S did not affect caspase-3 activation. No sex-specific differences were detected.

Schlussfolgerung/Diskussion

In the toxicity study, 10 µg/g bodyweight DHEA seems to reduce neuronal apoptosis in grey matter compared to controls. Since this result was only found in one region of grey matter, the clinical relevance of this finding is uncertain. Neonatal mouse pups with hypoxic-ischemic brain injury did not benefit from a single intraperitoneal injection of various concentrations of DHEA or DHEA-S. Further studies are required.

review
Erstautor*in ist unter 35 Jahre alt
Autor*in 1Julia Saurer Medizinische Universität Innsbruck/ Department für Pädiatrie II
Autor*in 2Sandra Bergerweiß Medizinische Universität Innsbruck/ Department für Pädiatrie II
Autor*in 3Martina Urbanek Medizinische Universität Innsbruck/ Department für Pädiatrie II
Autor*in 4Eva Huber Medizinische Universität Innsbruck/ Department für Pädiatrie II
Autor*in 5Ursula Kiechl-Kohlendorfer Medizinische Universität Innsbruck/ Department für Pädiatrie II
Autor*in 6Elke Griesmaier Medizinische Universität Innsbruck/ Department für Pädiatrie II
Autor*in 7Anna Posod Medizinische Universität Innsbruck/ Department für Pädiatrie II