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Multiple Antenatal Dexamethasone Treatment Alters Brain Vessel Differentiation in Newborn Mouse Pups

Please always quote using this URN: urn:nbn:de:bvb:20-opus-125471
  • Antenatal steroid treatment decreases morbidity and mortality in premature infants through the maturation of lung tissue, which enables sufficient breathing performance. However, clinical and animal studies have shown that repeated doses of glucocorticoids such as dexamethasone and betamethasone lead to long-term adverse effects on brain development. Therefore, we established a mouse model for antenatal dexamethasone treatment to investigate the effects of dexamethasone on brain vessel differentiation towards the blood-brain barrier (BBB)Antenatal steroid treatment decreases morbidity and mortality in premature infants through the maturation of lung tissue, which enables sufficient breathing performance. However, clinical and animal studies have shown that repeated doses of glucocorticoids such as dexamethasone and betamethasone lead to long-term adverse effects on brain development. Therefore, we established a mouse model for antenatal dexamethasone treatment to investigate the effects of dexamethasone on brain vessel differentiation towards the blood-brain barrier (BBB) phenotype, focusing on molecular marker analysis. The major findings were that in total brains on postnatal day (PN) 4 triple antenatal dexamethasone treatment significantly downregulated the tight junction protein claudin-5, the endothelial marker Pecam-1/CD31, the glucocorticoid receptor, the NR1 subunit of the N-methyl-D-aspartate receptor, and Abc transporters (Abcb1a, Abcg2 Abcc4). Less pronounced effects were found after single antenatal dexamethasone treatment and in PN10 samples. Comparisons of total brain samples with isolated brain endothelial cells together with the stainings for Pecam-1/CD31 and claudin-5 led to the assumption that the morphology of brain vessels is affected by antenatal dexamethasone treatment at PN4. On the mRNA level markers for angiogenesis, the sonic hedgehog and the Wnt pathway were downregulated in PN4 samples, suggesting fundamental changes in brain vascularization and/or differentiation. In conclusion, we provided a first comprehensive molecular basis for the adverse effects of multiple antenatal dexamethasone treatment on brain vessel differentiation.show moreshow less

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Metadaten
Author: Winfried Neuhaus, Marian Schlundt, Markus Fehrholz, Alexander Ehrke, Steffen Kunzmann, Stefan Liebner, Christian P. Speer, Carola Y. Förster
URN:urn:nbn:de:bvb:20-opus-125471
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004)
Language:English
Parent Title (English):PLoS One
Year of Completion:2015
Volume:10
Issue:8
Pagenumber:e0136221
Source:PLoS ONE 10(8): e0136221. doi:10.1371/journal.pone.0136221
DOI:https://doi.org/10.1371/journal.pone.0136221
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:angiogenesis; central nervous system; endothelial cells; mouse models; pregnancy; protein expression; sheep; tight junctions
Release Date:2016/01/26
Embargo Date:2016/01/26
EU-Project number / Contract (GA) number:241778
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung