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Expression of the Nrf2-system at the blood-CSF barrier is modulated by neonatal inflammation and hypoxia-ischemia

D'Angelo, B;Ek, CJ;Sandberg, M;Mallard, C;

Transcription factor NF-E2-related factor-2 (Nrf2) is a key regulator of endogenous anti-oxidant systems shown to play a neuroprotective role in the adult by preserving blood-brain barrier function. The choroid plexus, site for the blood-CSF barrier, has been suggested to be particularly important in maintaining brain barrier function in development. We investigated the expression of Nrf2- and detoxification-system genes in choroid plexus following systemic LPS injections, unilateral cerebral hypoxia-ischemia (HI) as well as the combination of LPS and HI (LPS/HI). Plexuses were collected at different time points after LPS, HI and LPS/HI in 9-day old mice. mRNA levels of Nrf2 and many of its target genes were analyzed by quantitative PCR. Cell death was analyzed by caspase-3 immunostaining and TUNEL. LPS caused down-regulation of the Nrf2-system genes while HI increased expression at earlier time points. LPS exposure prior to HI prevented many of the HI-induced gene increases. None of the insults resulted in any apparent cell death to choroidal epithelium. These data imply that the function of the inducible anti-oxidant system in the choroid plexus is down-regulated by inflammation, even if choroid cells are not structurally damaged. Further, LPS prevented the endogenous antioxidant response following HI, suggesting the possibility that the choroid plexus may be at risk if LPS is united with an insult that increases oxidative stress such as hypoxia-ischemia.