Protective effect of prostaglandin I(2) analogs on ischemic delayed neuronal damage in gerbils.
We found a novel subtype of prostaglandin (PG) I(2) receptor (IP(2)) expressed in the central nervous system. Recently we have demonstrated that (15R)-16-m-tolyl-17,18,19, 20-tetranorisocarbacyclin (15R-TIC) and 15-deoxy-16-m-tolyl-17,18,19, 20-tetranorisocarbacyclin (15-deoxy-TIC), IP(2)-specific ligands, significantly prevented high (50%) oxygen-induced apoptotic neuronal death in cultured hippocampal neurons. We report here a potent neuroprotective effect of such analogs on delayed neuronal death of hippocampal CA1 neurons following transient ischemia for 3 min in gerbils. (15S)-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin (15S-TIC), which nonselectively acts both on the PGI(2) receptor expressed in the peripheral tissue (IP(1)) and on IP(2), also showed a neuroprotective effect on such an ischemic model at higher doses than those for 15R-TIC and 15-deoxy-TIC. These PGI(2) analogs did not affect brain temperature, indicating that the agents showed the neuroprotective effect not by a hypothermic effect, but rather by the direct action on neurons.
Cui
Y
Y
Department of Neuroscience, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita-shi, Osaka, 565-0874, Japan.
Kataoka
Y
Y
Satoh
T
T
Yamagata
A
A
Shirakawa
N
N
Watanabe
Y
Y
Suzuki
M
M
Yanase
H
H
Kataoka
K
K
Watanabe
Y
Y
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005849:Gerbillinae; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D013237:Stereoisomerism
C401841:15-deoxy-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin; C119304:16-tolyl-17,18,19,20-tetranorisocarbacyclin; D018696:Neuroprotective Agents; D011464:Epoprostenol