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- D'angelo, Barbara, et al.
(author)
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Expression of the Nrf2-system at the blood-CSF barrier is modulated by neonatal inflammation and hypoxia-ischemia
- 2013
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In: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 36:3, s. 479-490
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Journal article (peer-reviewed)abstract
- ORIGINAL ARTICLE Expression of the Nrf2-system at the blood-CSF barrier is modulated by neonatal inflammation and hypoxia-ischemia Barbara D ’ Angelo & C. Joakim Ek & Mats Sandberg & Carina Mallard Received: 29 May 2012 /Revised: 14 September 2012 /Accepted: 10 October 2012 /Published online: 30 October 2012 # SSIEM and Springer Science+Business Media Dordrecht 2012 Abstract Transcription factor NF-E2-related factor-2 (Nrf2) is a key regulator of endogenous anti-oxidant sys- tems shown to play a neuroprotective role in the adult by preserving blood – brain barrier function. The choroid plex- us, 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 antioxi- dant 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.
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