NEUROPROTECTIVE PROPERTIES OF PROSTAGLANDIN I-2 IP RECEPTOR IN FOCAL CEREBRAL ISCHEMIA

作者：Saleem S; Shah Z A; Maruyama T; Narumiya S; Dore S^*

来源：Neuroscience, 2010, 170(1): 317-323.

DOI：10.1016/j.neuroscience.2010.06.060

• beraprost sodium
• cerebral ischemia
• middle cerebral artery occlusion
• mouse
• prostacyclin

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-/-) C57BI/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 mu g/kg p.o.) 30 min before tMCAO and post-treatment (100 mu g/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 mu g/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.

• 出版日期2010-9-29