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(American Journal of Pathology. 2004;164:1173-1181.)
© 2004 American Society for Investigative Pathology

Oxidized Low-Density Lipoprotein Is Present in Astrocytes Surrounding Cerebral Infarcts and Stimulates Astrocyte Interleukin-6 Secretion

Feng-Shiun Shie^*, M. Diana Neely, Izumi Maezawa^*, Hope Wu, Sandy J. Olson, Günther Jürgens, Kathleen S. Montine^* and Thomas J. Montine^*

From the Department of Pathology,^* University of Washington, Seattle, Washington; the Department of Pathology, Vanderbilt University, Nashville, Tennessee; and the Institute of Medical Biochemistry, Karl-Franzens Universitat Graz, Graz, Austria

Ischemic injury to brain is associated with both disruption of the blood-brain barrier and increased oxidative stress. Given the neurotoxicity associated with exposure to oxidized low-density lipoprotein (oxLDL) in vitro, we tested the hypothesis that oxLDL may be present in parenchymal cells of cerebrum after infarction and that oxLDL may influence the pathophysiology of cerebral infarction. Our results showed that the subacute phase of cerebral infarction in patients was characterized by the appearance of oxLDL epitopes in astrocytes, but not neurons or microglia, in the perinecrotic zone. We further demonstrated that minimally oxLDL was most effectively internalized by primary cultures of rat astrocytes, and that exposure to minimal oxLDL stimulated astrocyte interleukin-6 secretion but did not alter nitric oxide production. These results demonstrate for the first time that oxLDL is present in brain parenchyma of patients with ischemic infarction and suggest a potential mechanism by which oxLDL may activate innate immunity and thereby indirectly influence neuronal survival.

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