The neuroprotective effects of N1-dansyl-spermine in the gerbil model of cerebral ischaemia.
The effects of N1-dansyl-spermine, a polyamine antagonist, and ifenprodil, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, were investigated in the gerbil model of global cerebral ischaemia. Transient forebrain ischaemia was induced by 5-min bilateral occlusion of the common carotid arteries. N1-dansyl-spermine (2, 5 and 10 mg/kg) and ifenprodil (30 mg/kg) were administered intraperitoneally 30 min after bilateral carotid artery occlusion. On histological examination, 4 days (96 h) after ischaemia, there was a significant decrease in neuronal density of the hippocampal CA1 subfield. This reduction in neuronal density was attenuated in those animals treated with the 5 or 10 mg/kg dose of N1-dansyl-spermine and those treated with 30 mg/kg ifenprodil. However, unlike ifenprodil, N1-dansyl-spermine failed to attenuate the ischaemia-induced increase in locomotor activity. This demonstrates that polyamines play a significant role in the neuronal damage produced after cerebral ischaemia, while casting doubt on the suggestion that increased locomotor activity correlates with CA1 pyramidal cell damage.
Kirby
Brian P
BP
Department of Pharmacology, School of Pharmacy, Trinity College, Dublin 2, Ireland. bkirby@rcsi.ie
Shaw
Graham G
GG
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001831:Body Temperature; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002452:Cell Count / Q000379:methods; D003619:Dansyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use; D011073:Polyamines / Q000037:antagonists & inhibitors*; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
D003619:Dansyl Compounds; D018691:Excitatory Amino Acid Antagonists; C105932:N(1)-dansylspermine; D018696:Neuroprotective Agents; D010880:Piperidines; D011073:Polyamines; D013096:Spermine; C010739:ifenprodil