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Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic-ischemic brain injury.

Järlestedt, Katarina (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,Perinatal Center, University of Gothenburg, Gothenburg, Sweden
Rousset, Catherine I (author)
Centre for the Developing Brain, King's College, London, UK
Ståhlberg, Anders, 1975 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
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Sourkova, Hana (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
Atkins, Alison L (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
Thornton, Claire (author)
Centre for the Developing Brain, King's College, London, UK
Barnum, Scott R (author)
Department of Microbiology, University of Alabama, Birmingham, Alabama, USA
Wetsel, Rick A (author)
Research Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas–Houston, Houston, Texas, USA
Dragunow, Mike (author)
Department of Pharmacology and The National Research Centre for Growth and Development, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
Pekny, Milos, 1965 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
Mallard, Carina, 1963 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,Perinatal Center, University of Gothenburg, Gothenburg, Sweden
Hagberg, Henrik, 1955 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology,Institute of Neuroscience and Physiology, Department of Physiology,Perinatal Center, Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Centre for the Developing Brain, King's College, London, UK
Pekna, Marcela, 1966 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
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 (creator_code:org_t)
2013-06-04
2013
English.
In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - Bethesda : Wiley. - 1530-6860 .- 0892-6638. ; 27:9, s. 3797-3804
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.-Järlestedt, K., Rousset, C. I., Ståhlberg, A., Sourkova, H., Atkins, A. L., Thornton, C., Barnum, S. R., Wetsel, R. A., Dragunow, M., Pekny, M., Mallard, C., Hagberg, H., Pekna, M. Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic-ischemic brain injury.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Keyword

behavioral deficit
mice

Publication and Content Type

ref (subject category)
art (subject category)

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