T 48 h, and still elevated until 7 d after focal cerebral ischemia
T 48 h, and still elevated until 7 d after focal cerebral ischemia in rats, and COX2 was localized mainly in neurons. COX2 promoted the generation of free radicals when catalyzing AA to PGs, which is associated with the neurontoxicity of COX2 in cerebral ischemia [41]. Oxidative stress can directly induce the transcription of neuronal COX2 [42], which could lead to a vicious cycle associated with neurotoxicity. Our results demonstrated that the time-dependent upregulation of COX2 mRNA and the production of COX2 protein in rat hippocampus persisted for 7 d after ischemia. It suggested that increase of COX2 expression may involve in the brain injury. The reasons lied in the increased risk of cerebrovascular and cardiovascular complications in patients after long-term take of COX2 inhibitors are that COXYu et al. Behavioral and Brain Functions 2014, 10:42 http://www.behavioralandbrainfunctions.com/content/10/1/Page 8 ofinhibitors selectively inhibit PGI2 in the blood vessel wall without the concomitant inhibition of TXA2, and could promote hypertension and thrombosis, and increase cardiovascular risks [43]. Our results demonstrated an upregulation of COX2 expression and an upregulation of PGI2 and TXA2 levels at 20 min after global ischemia in rat hippocampus. It is reported that increased COX2 expression is associated with increased PGI2 and TXA2 levels [44]. PGI2 level significantly increased in rat hippocampus at 2 h with a peak at 48 h. Levels PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27484364 of TXA2 significantly decreased at 30 min and 2 h, thereafter began to increase at 6 h and peaked at 48 h. Similarly, Huttemeier et al. [24] found that the levels of PGI2 and TXA2 in the extracellular fluid increased significantly from 40 to 80 min and from 20 to 80 min after global cerebral I/R, respectively. It is unclear why the level of TXA2 decreased in the early period following I/R insult. Interestingly, the peak time is 7 d for COX2 expression and is 48 h for its downstream PGI2 and TXA2. The reason is unclear and should be explored in the future. Regarding their effects on cerebral I/R injury, the PGI2 and TXA2 bind to G protein-coupled receptors to exert different bio-effects. The infarct volumes and neurological deficit scores were significantly greater in IP-/- mice than in wildtype mice following focal cerebral ischemia [45]. Activation of IP receptor can SC144MedChemExpress SC144 attenuate anatomical and functional damages following ischemic stroke [45]. TXA2 receptor antagonist can ameliorate brain edema and cerebral infarct areas following focal cerebral ischemia [46], indicating that IP receptor is neuroprotective, while the TP receptor mediates harmful effects on cerebral ischemia injury. The increased ratio of PGI2/TXA2 is valuable for neuron-protection. It is reported that a favorable PGI2/ TXA2 ratio could protect the brain from injury [20,47]. PGI2/TXA2 ratio in rat hippocampus significantly increased from 30 min to 7 d after I/R injury compared with the sham-operated animals. The increased ratio may represent a physiological mechanism to protect the brain against the neuronal damage produced by I/R injury. Similarly, the levels of PGI2 and TXA2 and the ratio of PGI2/TXA2 were significantly higher in rat hippocampal slices of 18- and 24-month-old animals compared to 3-month-old animals, probably contributing to protecting the brain against aging-induced neuronal damage [48]. TP receptor antagonist and PGI2 alleviate brain injury by regulating collateral blood flow through vascular endothelium TP and.