Effects of somatostatin, octreotide and cortistatin on ischaemic neuronal damage following permanent middle cerebral artery occlusion in the rat.
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.
Rauca
C
C
Institute of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany. christine.rauca@medizin.uni-magdeburg.de
Schäfer
K
K
Höllt
V
V
D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage*; D001831:Body Temperature / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D006728:Hormones / Q000378:metabolism / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D020768:Middle Cerebral Artery; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D015282:Octreotide / Q000378:metabolism / Q000494:pharmacology*; D011759:Pyrrolidines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology*
D001572:Benzofurans; D006728:Hormones; D009479:Neuropeptides; D018696:Neuroprotective Agents; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C099323:cortistatin; D013004:Somatostatin; C067110:enadoline; D015282:Octreotide