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(Stroke. 1996;27:527-535.)
© 1996 American Heart Association, Inc.

Articles

Reactive Glia Express Cytosolic Phospholipase A2 After Transient Global Forebrain Ischemia in the Rat

James A. Clemens, PhD; Diane T. Stephenson, BS; E. Barry Smalstig, BS; Edda F. Roberts, MS; Edward M. Johnstone, MS; John D. Sharp, PhD; Sheila P. Little, PhD Ruth M. Kramer, PhD

From Eli Lilly and Company, CNS and Cardiovascular Divisions, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Ind.

Correspondence to Dr James A. Clemens, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.

Background and Purpose Phospholipid breakdown has been reported to be an early event in the brain after global cerebral ischemia. Our earlier observations showing the localization of cytosolic phospholipase A₂ (cPLA₂) to astrocytes in aged human brains and the intense glial activation observed after global forebrain ischemia prompted us to investigate the cellular localization of cPLA₂ in the rat brain subjected to global ischemia.

Methods Immunohistochemistry was performed in sections through the dorsal hippocampus in rats subjected to 30 minutes of four-vessel occlusion. PLA₂ was localized with the use of a highly selective antiserum. Double immunofluorescent localization was performed to colocalize cPLA₂ with various glial cell types. cPLA₂ levels were also measured by enzymatic assay and Western blot analysis.

Results A marked induction of cPLA₂ was observed in activated microglia and astrocytes in the CA1 hippocampal region at 72 hours after ischemia. Only a subset of astrocytes and microglia were immunoreactive for cPLA₂. Twenty-four hours after ischemia, numerous cPLA₂ immunoreactive astrocytes were observed. Western blot analysis of hippocampal homogenates at 72 hours after ischemia showed induction of a 100-kD band that comigrated with purified human cPLA₂, and a threefold induction in cPLA₂ activity was demonstrated by enzymatic assay.

Conclusions These results indicate that both reactive astrocytes and microglia contain elevated levels of cPLA₂. Induction of cPLA₂ was confined to areas of neurodegeneration and likely precedes its onset. The results suggest that reactive glia may play a role in the pathophysiology of delayed neuronal death after transient global forebrain ischemia.

Key Words: astrocytes • cerebral ischemia, global • occlusion • phospholipids • rats

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