Location of Repository

Acute Lipopolysaccharide-Mediated Injury in Neonatal White Matter Glia: Role of TNF-α, IL-1β, and Calcium

By Catherine Sherwin and Robert Fern

Abstract

Full text of this item is not currently available on the LRA. \ud The final published version is available at http://www.jimmunol.org/content/vol175/issue1/.Bacterial infection is implicated in the selective CNS white matter injury associated with cerebral palsy, a common birth disorder. Exposure to the bacterial endotoxin LPS produced death of white matter glial cells in isolated neonatal rat optic nerve (RON) (a model white matter tract), over a 180-min time course. A delayed intracellular Ca2+ concentration ([Ca2+]i) rise preceded cell death and both events were prevented by removing extracellular Ca2+. The cytokines TNF-α or IL-1β, but not IL-6, mimicked the cytotoxic effect of LPS, whereas blocking either TNF- α with a neutralizing Ab or IL-1 with recombinant antagonist prevented LPS cytotoxicity. Ultrastructural examination showed wide-scale oligodendroglial cell death in LPS-treated rat optic nerves, with preservation of astrocytes and axons. Fluorescently conjugated LPS revealed LPS binding on microglia and astrocytes in neonatal white and gray matter. Astrocyte binding predominated, and was particularly intense around blood vessels. LPS can therefore bind directly to developing white matter astrocytes and microglia to evoke rapid cell death in neighboring oligodendroglia via a calcium- and cytokine-mediated pathway. In addition to direct toxicity, LPS increased the degree of acute cell death evoked by ischemia in a calcium-dependent manner

Publisher: The American Association of Immunologists
Year: 2005
OAI identifier: oai:lra.le.ac.uk:2381/8031
Journal:
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://hdl.handle.net/2381/803... (external link)
  • http://www.jimmunol.org/conten... (external link)
  • http://www.jimmunol.org/conten... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.