C1 Esterase Inhibitor Reduces BBB Leakage and Apoptosis in the Hypoxic Developing Mouse Brain

Autor: Gudrun Boie, Susan Jung, Regina Trollmann, Hans-Georg Topf
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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