TY  - JOUR
A1  - Neuhaus, Winfried
A1  - Schlundt, Marian
A1  - Fehrholz, Markus
A1  - Ehrke, Alexander
A1  - Kunzmann, Steffen
A1  - Liebner, Stefan
A1  - Speer, Christian P.
A1  - Förster, Carola Y.
T1  - Multiple antenatal dexamethasone treatment alters brain vessel differentiation in newborn mouse pups
JF  - PLoS ONE
N2  - 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.
KW  - preterm birth
KW  - fetal lung
KW  - corticosteroids
KW  - glucocorticoids
KW  - exposure
KW  - endothelial cells
KW  - in vitro
KW  - barrier
KW  - expression
KW  - rat
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148268
VL  - 10
IS  - 8
ER  - 
TY  - JOUR
A1  - Ben-Kraiem, Adel
A1  - Sauer, Reine-Solange
A1  - Norwig, Carla
A1  - Popp, Maria
A1  - Bettenhausen, Anna-Lena
A1  - Atalla, Mariam Sobhy
A1  - Brack, Alexander
A1  - Blum, Robert
A1  - Doppler, Kathrin
A1  - Rittner, Heike Lydia
T1  - Selective blood-nerve barrier leakiness with claudin-1 and vessel-associated macrophage loss in diabetic polyneuropathy
JF  - Journal of Molecular Medicine
N2  - Diabetic polyneuropathy (DPN) is the most common complication in diabetes and can be painful in up to 26% of all diabetic patients. Peripheral nerves are shielded by the blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels. So far, there are conflicting results regarding the role and function of the BNB in the pathophysiology of DPN. In this study, we analyzed the spatiotemporal tight junction protein profile, barrier permeability, and vessel-associated macrophages in Wistar rats with streptozotocin-induced DPN. In these rats, mechanical hypersensitivity developed after 2 weeks and loss of motor function after 8 weeks, while the BNB and the blood-DRG barrier were leakier for small, but not for large molecules after 8 weeks only. The blood-spinal cord barrier remained sealed throughout the observation period. No gross changes in tight junction protein or cytokine expression were observed in all barriers to blood. However, expression of Cldn1 mRNA in perineurium was specifically downregulated in conjunction with weaker vessel-associated macrophage shielding of the BNB. Our results underline the role of specific tight junction proteins and BNB breakdown in DPN maintenance and differentiate DPN from traumatic nerve injury. Targeting claudins and sealing the BNB could stabilize pain and prevent further nerve damage.
KW  - macrophages
KW  - neuropathy
KW  - barrier
KW  - pain
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265237
VL  - 99
IS  - 9
ER  -