Time course change of COX2-PGI(2)/TXA(2) following global cerebral ischemia reperfusion injury in rat hippocampus

BACKGROUND: Neuroinflammation plays pivotal roles in the progression of cerebral ischemia injury. Prostaglandins (PGs) as the major inflammatory mediators in the brain participate in the pathophysiological processes of cerebral ischemia injury. Cyclooxygenase-2 (COX2) is the rate-limiting enzyme of PGs, and thus it is necessary to characterize of the expression patterns of COX2 and its downstream products at the same time in a cerebral ischemia/reperfusion (I/R) model. METHODS: The levels of prostacyclin (PGI(2)) and thromboxane (TXA(2)) and the expression of COX2 were detected in the rat hippocampus at different time points after reperfusion (30 min, 2 h, 6 h, 24 h, 48 h, 7 d, and 15 d). RESULTS: The COX2 mRNA and protein expressions in hippocampus both remarkably increased at 30 min, and peaked at 7 d after global cerebral I/R compared with the sham-operated group. The level of PGI(2) significantly increased at 2 h after reperfusion, with a peak at 48 h, but was still significantly higher than the sham-operated animals at 15 d. TXA(2) level decreased at 30 min and 2 h after reperfusion, but significantly increased at 6 h and peaked at 48 h. PGI(2)/TXA(2) ratio increased at 30 min after reperfusion, and peaked at 48 h compared with the sham-operated animals. CONCLUSIONS: I/R injury significantly increased the COX2 expression, PGI(2) and TXA(2) levels, and the PGI(2)/TXA(2) ratio in rat hippocampus in a time-dependent manner. As a consequence, the increased PGI(2) level and PGI(2)/TXA(2) ratio may represent a physiological mechanism to protect the brain against the neuronal damage produced by I/R injury.