Effects of intracerebroventricular galanin or a galanin receptor 2/3 agonist on the lesion induced by transient occlusion of the middle cerebral artery in female rats.
Several studies have shown that injury to the central and peripheral nervous system can increase expression of galanin, a 29 amino acid neuropeptide. Moreover, there is evidence that galanin, especially through its galanin receptor 2 (GalR2) receptor, plays a neuroprotective role in different injury models. However, direct studies of a possible neuroprotective effect of galanin in experimental stroke models are lacking. Galanin, a GalR2/3 agonist or artificial CSF was continuously infused intracerebroventricularly (i.c.v.) in naïve female rats after a 60min transient and focal occlusion of the middle cerebral artery. The animals were sacrificed, and the ischemic lesion was visualized using 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining. The lesion was 98% larger after i.c.v. administration of the GalR2/3 agonist (2.4nmol/day) seven days after occlusion compared to artificial CSF (p=0.023). No statistically significant differences were found after seven days in the groups treated with galanin in three different concentrations (0.24, 2.4 and 24nmol/day; p=0.939, 0.715 and 0.977, respectively). There was no difference in the size of the ischemic lesions measured after three days in the galanin-treated group (2.4nmol/d) compared to artificial CSF (p=0.925). The present results show, surprisingly, that a GalR2/3 agonist doubled the size of the ischemic lesion. Whether this effect primarily reflects the properties of the current model, species, gender and/or the mode of galanin administration, e.g. causing desensitization, or whether galanin indeed lacks neuroprotective effect of its own, remains to be corroborated.
Department of Clinical and Experimental Medicine/Division of Clinical Chemistry, Linköping University, Linköping, Sweden.
Lovisa
L
Holm
Elvar
E
Theodorsson
Tomas
T
Hökfelt
Annette
A
Theodorsson
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D005260:Female; D019004:Galanin / Q000008:administration & dosage* / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D057967:Infusions, Intraventricular; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044092:Receptor, Galanin, Type 2 / Q000819:agonists*; D044093:Receptor, Galanin, Type 3 / Q000819:agonists*
D044092:Receptor, Galanin, Type 2; D044093:Receptor, Galanin, Type 3; D019004:Galanin