The effects of TRH analogues on cerebral ischaemia produced by middle cerebral artery occlusion in the rat.
This study examined the effects of two stabilised analogues of TRH, RX 77368 and CG 3509, in a rat cerebral ischaemia model produced by unilateral occlusion of the middle cerebral artery. The analogues were given intraventricularly after artery occlusion. The extent of the cortical ischaemia was evaluated after 10 days by somatosensory evoked potential (SEP) recording, followed by tetrazolium staining of brain slices for NADH-diaphorase activity. RX 77368 (2 X 10 micrograms; 15 min, 24 h) significantly improved the survival rate, protected the SEP and reduced the area of infarct. In contrast, neither a smaller dose of RX 77368 (2 X 3 micrograms) nor a 4 h delay in the treatment had any significant beneficial effects. Although CG 3509 (2 X 10 micrograms) resulted in an apparent improvement in survival, its overall effects were not statistically significant. The findings indicate that stabilised TRH analogues may have beneficial effects when given to animals with focal cerebral ischaemia.
D000818:Animals; D002536:Cerebral Arteries; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism; D005073:Evoked Potentials, Somatosensory; D005260:Female; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013997:Time Factors
C036430:orotirelin; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D008058:Dihydrolipoamide Dehydrogenase; D011761:Pyrrolidonecarboxylic Acid