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.