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Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic‐ischemic brain injury
- Source :
- The FASEB Journal. 27:3797-3804
- Publication Year :
- 2013
- Publisher :
- Wiley, 2013.
-
Abstract
- Complement is an essential component of inflammation that plays a role in ischemic brain injury. Recent reports demonstrate novel functions of complement in normal and diseased CNS, such as regulation of neurogenesis and synapse elimination. Here, we examined the role of complement-derived peptide C3a in unilateral hypoxia-ischemia (HI), a model of neonatal HI encephalopathy. HI injury was induced at postnatal day 9 (P9), and loss of hippocampal tissue was determined on P31. We compared WT mice with transgenic mice expressing C3a under the control of glial fibrillary acidic protein promoter, which express biologically active C3a only in CNS and without the requirement of a priori complement activation. Further, we injected C3a peptide into the lateral cerebral ventricle of mice lacking the C3a receptor (C3aR) and WT mice and assessed HI-induced memory impairment 41 d later. We found that HI-induced tissue loss in C3a overexpressing mice was reduced by 50% compared with WT mice. C3a peptide injected 1 h after HI protected WT but not C3aR-deficient mice against HI-induced memory impairment. Thus, C3a acting through its canonical receptor ameliorates behavioral deficits after HI injury, and C3aR is a novel therapeutic target for the treatment of neonatal HI encephalopathy.
- Subjects :
- Genetically modified mouse
medicine.medical_specialty
Hippocampus
Mice, Transgenic
chemical and pharmacologic phenomena
Inflammation
Biochemistry
Mice
Internal medicine
Genetics
Animals
Medicine
RNA, Messenger
Receptor
Molecular Biology
Neurons
biology
Glial fibrillary acidic protein
business.industry
Macrophages
Neurogenesis
Immunohistochemistry
Receptors, Complement
Complement system
Mice, Inbred C57BL
Endocrinology
Animals, Newborn
Astrocytes
Hypoxia-Ischemia, Brain
Immunology
Complement C3a
biology.protein
C3a receptor
medicine.symptom
business
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....c8b6ebee51490a54f88625ed39767bd2