Transcriptome profiling of the newborn mouse brain after hypoxia-reoxygenation: Hyperoxic reoxygenation induces inflammatory and energy failure responsive genes

Background:

Supplemental oxygen used during resuscitation can be detrimental to the newborn brain. The aim was to determine how different oxygen therapies affect gene transcription in a hypoxia–reoxygenation model.

Methods:

C57BL/6 mice (n = 56), postnatal day 7, were randomized either to 120 min of hypoxia 8% O2 followed by 30 min of reoxygenation with 21, 40, 60, or 100% O2, or to normoxia followed by 30 min of 21 or 100% O2. Affymetrix 750k expression array was applied with RT-PCR used for validation. Histopathology and immunohistochemistry 3 d after hypoxia–reoxygenation compared groups reoxygenated with 21 or 100% O2 with normoxic controls (n = 22).

Results:

In total, ~81% of the gene expression changes were altered in response to reoxygenation with 60 or 100% O2 and constituted many inflammatory-responsive genes (i.e., C5ar2, Stat3, and Ccl12). Oxidative phosphorylation was downregulated after 60 or 100% O2. Iba1+ cells were significantly increased in the striatum and hippocampal CA1 after both 21 and 100% O2.

Conclusion:

In the present model, hypoxia–reoxygenation induces microglial accumulation in subregions of the brain. The transcriptional changes dominating after applying hyperoxic reoxygenation regimes include upregulating genes related to inflammatory responses and suppressing the oxidative phosphorylation pathway.