This study investigated whether peptides acting at somatostatin receptors, such as somatostatin-14, octreotide or cortistatin-14, can influence the extent of brain damage after focal ischaemia in rats. The intracerebroventricular application of 0.1 or 1.0 nmol somatostatin-14 5 min after middle cerebral artery occlusion significantly reduced the infarct size assessed 7 days after the insult (by 47% and 57% of the saline control), whereas 10.0 nmol had no significant protective effect (9% reduction). A similar dose/response relationship was obtained after intracerebroventricular injection of octreotide. The lower doses of 0.1 or 1.0 nmol afforded significant neuroprotection (reduction of the infarct size by 72 and 57%), whereas 10 nmol actually increased the infarct size up to 348%. Cortistatin-14 (10 nmol) decreased the ischaemic damage by 52%. For comparison with the neuropeptides acting on somatostatin receptors, the kappa opiate agonist enadoline (10 nmol) also had a significant protective effect against the development of focal ischaemia; the extent of the brain damage was reduced by 60% after intracerebroventricular injection.
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