Time course change of COX2-PGI2/TXA2 following global cerebral ischemia reperfusion injury in rat hippocampus

Abstract

BackgroundNeuroinflammation 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.MethodsThe levels of prostacyclin (PGI2) and thromboxane (TXA2) 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).ResultsThe 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 PGI2 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. TXA2 level decreased at 30 min and 2 h after reperfusion, but significantly increased at 6 h and peaked at 48 h. PGI2/TXA2 ratio increased at 30 min after reperfusion, and peaked at 48 h compared with the sham-operated animals.ConclusionsI/R injury significantly increased the COX2 expression, PGI2 and TXA2 levels, and the PGI2/TXA2 ratio in rat hippocampus in a time-dependent manner. As a consequence, the increased PGI2 level and PGI2/TXA2 ratio may represent a physiological mechanism to protect the brain against the neuronal damage produced by I/R injury.

MicroRNA-132 modifies angiogenesis in patients with ischemic cerebrovascular disease by suppressing the NF‑κB and VEGF pathway

“…The promotion of Cox-2 is part of the development of neuronal apoptosis in brain ischemia and neurodegenerative diseases (35). NF-κB exists in almost all types of cells.…”

Retracted: Protective effects of microRNA‐431 against cerebral ischemia‐reperfusion injury in rats by targeting the Rho/Rho‐kinase signaling pathway

“…Cerebral ischemia‐reperfusion injury is defined as a permanent or transient cerebral blood flow reduction or pause that impedes the central nervous system to meet the functional or metabolic demand (Yu et al, ). It occurred when blood vessel was blocked and further exacerbated by sudden recovery of the blood supply, causing the dysfunction of neurons, glia cells, and cerebral blood vessels (Ioroi et al, ; Tang et al, ).…”

“…Cerebral ischemia‐reperfusion injury‐induced ischemic stroke has been reported to become the third leading cause of death, only after heart disease and cancer (Liang, Shi, Luo, & Yang, ). Cerebral ischemia‐perfusion injury is featured with high morbidity, disability, and mortality and accounts for about 83% of all stroke cases (Lu et al, ; Yu et al, ). Increasing evidences have demonstrated that the mechanism of ischemia‐reperfusion injury was closely related with cell apoptosis and pyramidal neurons in hippocampal CA1 region were said to be the most vulnerable neurocytes to ischemia/reperfusion injury‐induced apoptosis (Yang et al, ).…”

Tetrandrine alleviates symptoms of rheumatoid arthritis in rats by regulating the expression of cyclooxygenase‑2 and inflammatory factors

“…COX-2 is a major inflammatory enzyme that has a rate-limiting role in the synthesis of prostaglandin (44). COX-2 also converts arachidonic acid into prostaglandin endoperoxides, which are subsequently converted to thromboxane A2 and prostaglandin to exert inflammatory effects (45).…”