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Göteborgs universitets publikationer

Lipopolysaccharide Sensitizes Neonatal Hypoxic-Ischemic Brain Injury in a MyD88-Dependent Manner

Författare och institution:
Xiaoyang Wang (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); L. Stridh (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Wenli Li (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); J. Dean (-); A. Elmgren (-); L. Gan (-); Kristina Eriksson (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); Henrik Hagberg (Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa); Carina Mallard (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi)
Publicerad i:
Journal of Immunology, 183 ( 11 ) s. 7471-7477
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Neurological deficits in children, including cerebral palsy, are associated with prior infection during the perinatal period. Experimentally, we have shown that pre-exposure to the Gram-negative component LPS potentiates hypoxic-ischemic (HI) brain injury in newborn animals. LPS effects are mediated by binding to TLR4, which requires recruitment of the MyD88 adaptor protein or Toll/IL-1R domain-containing adapter inducing IFN-beta for signal transduction. In this study, we investigated the role of MyD88 in neonatal brain injury. MyD88 knockout (MyD88 KO) and wild-type mice were subjected to left carotid artery ligation and 10% O(2) for 50 min on postnatal day 9. LPS or saline were administered i.p. at 14 h before HI. At 5 days after HI in wild-type mice, LPS in combination with HI caused a significant increase in gray and white matter tissue loss compared with the saline-HI group. By contrast, in the MyD88 KO mice there was no potentiation of brain injury with LPS-HI. MyD88 KO mice exhibited reduced NFkappaB activation and proinflammatory cytokine-chemokine expression in response to LPS. The number of microglia and caspase-3 activation was increased in the brain of MyD88 KO mice after LPS exposure. Collectively, these findings indicate that MyD88 plays an essential role in LPS-sensitized HI neonatal brain injury, which involves both inflammatory and caspase-dependent pathways.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Postens nummer:
Posten skapad:
2009-11-23 16:25
Posten ändrad:
2010-02-22 12:05

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