Lipocortin - 1 Is an Endogenous Inhibitor of Ischemic Damage in the Rat Brain By Jane

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 ofischemia. Ischemia caused increased expression of lipocortin-1 around the area of infarction as demonstrated by immunocytochemistry. Intracerebroventricular injection of neutralizing antilipocortin-1 fragment antiserum increased the size ofinfarct (53%) and the development ofedema (29%). These findings indicate that lipocortin-1 is an endogenous inhibitor of cerebral ischemia with considerable therapeutic potential .