Abstract
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. Intracerebroventricular 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.
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- Brönnegård M., Andersson O., Edwall D., Lund J., Norstedt G., Carstedt-Duke J. Human calpactin II (lipocortin I) messenger ribonucleic acid is not induced by glucocorticoids. Mol Endocrinol. 1988 Aug;2(8):732–739. doi: 10.1210/mend-2-8-732. [DOI] [PubMed] [Google Scholar]
- Bullock R., Graham D. I., Chen M. H., Lowe D., McCulloch J. Focal cerebral ischemia in the cat: pretreatment with a competitive NMDA receptor antagonist, D-CPP-ene. J Cereb Blood Flow Metab. 1990 Sep;10(5):668–674. doi: 10.1038/jcbfm.1990.120. [DOI] [PubMed] [Google Scholar]
- Carey F., Forder R., Edge M. D., Greene A. R., Horan M. A., Strijbos P. J., Rothwell N. J. Lipocortin 1 fragment modifies pyrogenic actions of cytokines in rats. Am J Physiol. 1990 Aug;259(2 Pt 2):R266–R269. doi: 10.1152/ajpregu.1990.259.2.R266. [DOI] [PubMed] [Google Scholar]
- Cirino G., Peers S. H., Flower R. J., Browning J. L., Pepinsky R. B. Human recombinant lipocortin 1 has acute local anti-inflammatory properties in the rat paw edema test. Proc Natl Acad Sci U S A. 1989 May;86(9):3428–3432. doi: 10.1073/pnas.86.9.3428. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dumuis A., Pin J. P., Oomagari K., Sebben M., Bockaert J. Arachidonic acid released from striatal neurons by joint stimulation of ionotropic and metabotropic quisqualate receptors. Nature. 1990 Sep 13;347(6289):182–184. doi: 10.1038/347182a0. [DOI] [PubMed] [Google Scholar]
- Hirata F. The regulation of lipomodulin, a phospholipase inhibitory protein, in rabbit neutrophils by phosphorylation. J Biol Chem. 1981 Aug 10;256(15):7730–7733. [PubMed] [Google Scholar]
- Johnson M. D., Kamso-Pratt J. M., Whetsell W. O., Jr, Pepinsky R. B. Lipocortin-1 immunoreactivity in the normal human central nervous system and lesions with astrocytosis. Am J Clin Pathol. 1989 Oct;92(4):424–429. doi: 10.1093/ajcp/92.4.424. [DOI] [PubMed] [Google Scholar]
- Johnson M. D., Kamso-Pratt J., Pepinsky R. B., Whetsell W. O., Jr Lipocortin-1 immunoreactivity in central and peripheral nervous system glial tumors. Hum Pathol. 1989 Aug;20(8):772–776. doi: 10.1016/0046-8177(89)90071-3. [DOI] [PubMed] [Google Scholar]
- Lynch M. A., Voss K. L. Arachidonic acid increases inositol phospholipid metabolism and glutamate release in synaptosomes prepared from hippocampal tissue. J Neurochem. 1990 Jul;55(1):215–221. doi: 10.1111/j.1471-4159.1990.tb08841.x. [DOI] [PubMed] [Google Scholar]