C1 Esterase Inhibitor Reduces BBB Leakage and Apoptosis in the Hypoxic Developing Mouse Brain
Autor: | Gudrun Boie, Susan Jung, Regina Trollmann, Hans-Georg Topf |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Subventricular zone Apoptosis Nerve Tissue Proteins S100 Calcium Binding Protein beta Subunit Matrix metalloproteinase Occludin Neuroprotection Mitochondrial Proteins 03 medical and health sciences Cellular and Molecular Neuroscience Mice Random Allocation 0302 clinical medicine Pregnancy Internal medicine medicine Animals RNA Messenger Hypoxia Hypoxia Brain TUNEL assay Tight Junction Proteins Tight junction Chemistry Brain Gene Expression Regulation Developmental Membrane Proteins Dual Specificity Phosphatase 1 Hypoxia (medical) Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Neurology Animals Newborn Blood-Brain Barrier Molecular Medicine Female medicine.symptom Inflammation Mediators Complement C1 Inhibitor Protein 030217 neurology & neurosurgery |
Zdroj: | Neuromolecular medicine. 22(1) |
ISSN: | 1559-1174 |
Popis: | Inflammatory pathways involved in blood–brain barrier (BBB) vulnerability and hypoxic brain oedema in models of perinatal brain injury seem to provide putative therapeutic targets. To investigate impacts of C1-esterase inhibitor (C1-INH; 7.5–30 IU/kg, i.p.) on functional BBB properties in the hypoxic developing mouse brain (P7; 8% O2 for 6 h), expression of pro-apoptotic genes (BNIP3, DUSP1), inflammatory markers (IL-1s, TNF-alpha, IL-6, MMP), and tight junction proteins (ZO-1, occludin, claudin-1, -5), and S100b protein concentrations were analysed after a regeneration period of 24 h. Apoptotic cell death was quantified by CC3 immunohistochemistry and TUNEL staining. In addition to increased apoptosis in the parietal cortex, hippocampus, and subventricular zone, hypoxia significantly enhanced the brain-to-plasma albumin ratio, the cerebral S100b protein levels, BNIP3 and DUSP1 mRNA concentrations as well as mRNA expression of pro-inflammatory cytokines (IL-1s, TNF-alpha). In response to C1-INH, albumin ratio and S100b concentrations were similar to those of controls. However, the mRNA expression of BNIP3 and DUSP1 and pro-inflammatory cytokines as well as the degree of apoptosis were significantly decreased compared to non-treated controls. In addition, occludin mRNA levels were elevated in response to C1-INH (p |
Databáze: | OpenAIRE |
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