Lipocortin-1 is an endogenous inhibitor of ischemic damage in the rat brain

Jane K. Relton, Paul J L M Strijbos, Celestine T. O'Shaughnessy, Frank Carey, Robert A. Forder, Fred J H Tilders, Nancy J. Rothwell

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Lipocortin-1 (annexin-1) is an endogenous peptide with antiinflammatory properties. We have previously demonstrated lipocortin immunoreactivity in certain glial cells and neurons in the rat brain (Strijbos, P. J. L. M., F. J. H. Tilders, F. Carey, R. Forder, and N. J. Rothwell. 1990. Brain Res. In press.), and have shown that an NH2-terminal fragment (1-188) of lipocortin-1 inhibits the central and peripheral actions of cytokines on fever and thermogenesis in the rat in vivo (Carey, F., R. Forder, M. D. Edge, A. R. Greene, M. A. Horan, P. J. L. M. Strijbos, and N. J. Rothwell. 1990. Am. J. Physiol. 259:R266; and Strijbos, P. J. L. M., J. L. Browning, M. Ward, R. Forder, F. Carey, M. A. Horan, and N. J. Rothwell. 1991. Br. J. Pharmacol. In press.). We now report that intracerebroventricular administration of lipocortin-1 fragment causes marked inhibition of infarct size (60%) and cerebral edema (46%) measured 2 h after cerebral ischemia (middle cerebral artery occlusion) in the rat in vivo. The lipocortin-1 fragment was effective when administered 10 min after induction of ischemia. Ischemia caused increased expression of lipocortin-1 around the area of infarction as demonstrated by immunocytochemistry. Intra-cerebroventricular injection of neutralizing antilipocortin-1 fragment antiserum increased the size of infarct (53%) and the development of edema (29%). These findings indicate that lipocortin-1 is an endogenous inhibitor of cerebral ischemia with considerable therapeutic potential.
Original languageEnglish
Pages (from-to)305-310
Number of pages5
JournalJournal of Experimental Medicine
Issue number2
Publication statusPublished - 1991


  • Animals
  • Annexins
  • physiology: Brain
  • physiopathology: Brain Edema
  • physiopathology: Brain Ischemia
  • pharmacology: Calcium-Binding Proteins
  • drug effects: Cell Survival
  • physiopathology: Cerebral Infarction
  • Fluorescent Antibody Technique
  • Injections, Intraventricular
  • Male
  • Rats
  • Rats, Inbred Strains
  • administration & dosage: Recombinant Proteins
  • Support, Non-U.S. Gov't


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