Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/8031
Title: Acute Lipopolysaccharide-Mediated Injury in Neonatal White Matter Glia: Role of TNF-α, IL-1β, and Calcium
Authors: Sherwin, Catherine
Fern, Robert
First Published: 1-Jul-2005
Publisher: The American Association of Immunologists
Citation: The Journal of Immunology, 2005, 175 (1), pp. 155-161
Abstract: 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.
ISSN: 0022-1767
Links: http://www.jimmunol.org/content/vol175/issue1/
http://hdl.handle.net/2381/8031
Type: Article
Description: Full text of this item is not currently available on the LRA. The final published version is available at http://www.jimmunol.org/content/vol175/issue1/.
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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