Neuroprotective properties of prostaglandin I2 IP receptor in focal cerebral ischemia.
We and others have identified that inhibition of cyclooxygenase might not be the optimal approach to limiting brain damage after stroke. Now we are investigating the unique properties of the various prostaglandin receptors to determine whether blocking those that mediate toxicity or stimulating those that reduce toxicity will improve neurological outcomes. Here, we determined the respective contribution of the prostaglandin I(2) (PGI(2)) receptor in transient middle cerebral artery (MCA) occlusion (tMCAO) and permanent MCAO (pMCAO) preclinical stroke models by using male wildtype (WT) and IP receptor knockout (IP(-/-)) C57Bl/6 mice. In addition, we investigated the putative preventive and therapeutic effects of the IP receptor agonist beraprost. The infarct volumes and neurological deficit scores (NDS) were significantly greater in IP(-/-) than in WT mice after both tMCAO and pMCAO. Interestingly, beraprost pretreatment (50 or 100 microg/kg p.o.) 30 min before tMCAO and post-treatment (100 microg/kg p.o.) at 2 or 4.5 h of reperfusion significantly reduced the neurological deficit score and infarct volume in WT mice. Post-treatment with beraprost (100 microg/kg p.o.) 4.5 h after pMCAO also significantly decreased neurological deficits and infarct volume in WT mice. Together, these novel findings suggest for the first time that PGI(2) IP receptor activation can attenuate anatomical and functional damage following ischemic stroke.
Saleem
S
S
Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Shah
Z A
ZA
Maruyama
T
T
Narumiya
S
S
Doré
S
S
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control*; D015331:Cohort Studies; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D044006:Receptors, Epoprostenol / Q000819:agonists* / Q000502:physiology*
D018696:Neuroprotective Agents; D044006:Receptors, Epoprostenol; C048081:beraprost; D011464:Epoprostenol