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Göteborgs universitets publikationer

Innate defence regulator peptide 1018 protects against perinatal brain injury.

Författare och institution:
Hayde Bolouri (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Karin Sävman (Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa, Avdelningen för pediatrik); Wei Wang (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Anitha Thomas (-); Norbert Maurer (-); Edie Dullaghan (-); Christopher D Fjell (-); Joakim Ek (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Henrik Hagberg (Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa, Avdelningen för obstetrik och gynekologi); Robert E W Hancock (-); Kelly Brown (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); Carina Mallard (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi)
Publicerad i:
Annals of neurology, 75 ( 3 ) s. 395–410
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Objective: There is currently no pharmacological treatment that provides protection against brain injury in neonates. It is known that activation of an innate immune response is a key, contributing factor in perinatal brain injury, therefore, the neuroprotective therapeutic potential of innate defence regulator peptides (IDRs) was investigated. Methods: The anti-inflammatory effects of three IDRs was measured in LPS-activated murine microglia. IDRs were then assessed for their ability to confer neuroprotection in vivo when given 3h after neonatal brain injury in a clinically relevant model that combines an inflammatory challenge (LPS) with hypoxia-ischemia (HI). To gain insight into peptide-mediated effects on LPS-induced inflammation and neuroprotective mechanisms, global cerebral gene expression patterns were analyzed in pups that were treated with IDR-1018 either 4 h before LPS or 3h after LPS+HI. Results: IDR-1018 reduced inflammatory mediators produced by LPS-stimulated microglia cells in vitro and modulated LPS-induced neuroinflammation in vivo. When administered 3h after LPS+HI, IDR-1018 exerted effects on regulatory molecules of apoptotic (for e.g. Fadd and Tnfsf9) and inflammatory (for e.g. IL-1, TNF-α, chemokines and cell adhesion molecules) pathways and showed marked protection of both white and grey brain matter. Interpretation: IDR-1018 supresses pro-inflammatory mediators and cell injurious mechanisms in the developing brain, and post-insult treatment is efficacious in reducing LPS-induced hypoxic-ischemic brain damage. IDR-1018 is effective in the brain when given systemically, confers neuroprotection of both grey and white matter, and lacks significant effects on the brain under normal conditions. Thus this peptide provides the features of a promising neuroprotective agent in newborns with brain injury. ANN NEUROL 2013. © 2013 American Neurological Association.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
Klinisk medicin ->
Postens nummer:
Posten skapad:
2014-02-24 15:24
Posten ändrad:
2014-05-12 08:21

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