Induction of prostacyclin/PGI sub(2) synthase expression after cerebral ischemia-reperfusion

• Published in: Journal of cerebral blood flow and metabolism Vol. 26; no. 4; pp. 491 - 501
• Main Authors: Fang, Yao-Ching, Wu, Jui-Sheng, Chen, Jean-Ju, Cheung, Wai-Mui, Tseng, Ping-Hui, Tam, Ka-Bik, Shyue, Song-Kun, Chen, Jin-Jer, Lin, Teng-Nan
• Format: Journal Article
• Language: English
• Published: 01.04.2006
• ISSN: 0271-678X
• DOI: 10.1038/sj.jcbfm.9600205

Prostacyclin (PGI sub(2)), a potent vasodilator and inhibitor of platelet aggregation and leukocyte activation, is crucial in vascular diseases such as stroke. Prostacyclin synthase (PGIS) is the key enzyme for PGI sub(2) synthesis. Although expression of PGIS was noted in the brain, its role in ischemic insult remains unclear. Here we reported the temporal and spatial expression of PGIS mRNA and protein after 60-min transient ischemia. Northern blot and in situ hybridization revealed a delayed increase of PGIS mRNA in the ischemic cortex at 24- to 72-h after ischemia; PGIS was detected mainly in the ipsilateral penumbra area, pyriform cortex, hippocampus, and leptomeninges. Western blot and immunohistochemical analysis revealed that PGIS proteins were expressed temporally and spatially similar to PGIS mRNA. PGIS was heavily colocalized with PECAM-1 to endothelial cells at the leptomeninges, large and small vessels, and localized to neuronal cells, largely at the penumbra area. A substantial amount of PGIS was also detected in the macrophage and glial cells. To evaluate its role against ischemic infarct, we overexpressed PGIS by adenoviral gene transfer. When infused 72h before ischemia (- 72h), Adv-PGIS reduced infarct volume by similar to 50%. However, it had no effect on infarct volume when infused immediately after ischemia (0h). Eicosanoid analysis revealed selective elevation of PGI sub(2) at - 72h while PGI sub(2) and TXB sub(2) were both elevated at 0h, altering the PGI sub(2)/thromboxane A sub(2) (TXA sub(2)) ratio from 10 to 4. These findings indicate that PGIS protects the brain by enhancing PGI sub(2) synthesis and creating a favorable PGI sub(2)/TXA sub(2) ratio.Journal of Cerebral Blood Flow & Metabolism (2006) 26, 491-501. doi:10.1038/sj.jcbfm.9600205; published online 10 August 2005