Protective effects of cortistatin(CST-14) against kainate-induced neurotoxicity in rat brain

Cortistatin (CST-14) is a recently discovered endogenous peptide which shares similarity to somatostatin and binds to somatostatin receptors. In this study, we show that CST-14 exhibits anticonvulsive and neuroprotective effects in rats. Injection of rats with kainic acid (KA; 10 mg/kg; i.p.) generated a strong seizure activity which was attenuated by the i.c.v, application of 1 and 10 nmol CST-14 when given 10 min before KA. Moreover, 3 days after KA injection, a marked loss of neurons in cortex and hippocampus of rats was observed which was inhibited by pretreatment with CST-14. An immunohistochemical analysis using specific antibodies revealed that KA reduced immunoactive sst(2A) and sst(3) somatostatin receptors in the hippocampus-an effect which was largely prevented by pretreatment with CST-14. Superfusion of hippocampal slices with CST-14 also reduced the stimulated release of H-3-D-aspartate. We conclude that CST-14 exerts neuroprotective effects by binding to somatostatin receptors which in turn leads to a reduced release of excitotoxic neurotransmitters. (C) 1998 Elsevier Science B.V. Al rights reserved.