Protective effect of prostaglandin I(2) analogs on ischemic delayed neuronal damage in gerbils

  • Biochem Biophys Res Commun. 1999 Nov 19;265(2):301-4. doi: 10.1006/bbrc.1999.1671.
Y Cui  1 ,  Y Kataoka ,  T Satoh ,  A Yamagata ,  N Shirakawa ,  Y Watanabe ,  M Suzuki ,  H Yanase ,  K Kataoka ,  Y Watanabe
Affiliations
  • 1. Department of Neuroscience, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita-shi, Osaka, 565-0874, Japan.
PMID: 10558861 DOI: 10.1006/bbrc.1999.1671
Abstract

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.

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