RESUMEN
Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc., a long-established traditional Chinese medicine, is beneficial to the treatment of neurodegenerative diseases including ischemic stroke. In particular, its major component, cornel iridoid glycoside (CIG), was evidenced to exhibit neuroprotective effects against cerebral ischemic/reperfusion injury (CIR/I). Aimed to explore the effects of the CIG on brain edema of the CIR/I rats, the CIG was analyzed with the main constituents by using HPLC. The molecular docking analysis was performed between the CIG constituents and AQP4-M23. TGN-020, an AQP4 inhibitor, was used as a comparison. In the in vivo experiments, the rats were pre-treated with the CIG and were injured by performing middle cerebral artery occlusion/reperfusion (MCAO/R). After 24â¯h, the rats were examined for neurological function, pathological changes, brain edema, and polarized Aqp4 expressions in the brain. The HPLC analysis indicated that the CIG was composed of morroniside and loganin. The molecular docking analysis showed that both morroniside and loganin displayed lower binding energies to AQP4-M23 than TGN-020. The CIG pre-treated rats exhibited fewer neurological function deficits, minimized brain swelling, and reduced lesion volumes compared to the MCAO/R rats. In the peri-infarct and infarct regions, the CIG pre-treatment restored the polarized Aqp4 expression which was lost in the MCAO/R rats. The results suggested that the CIG could attenuate brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized Aqp4 through the interaction of AQP4-M23 with morroniside and loganin.
RESUMEN
Background: Restoration of blood supply is a desired goal for the treatment of acute ischemic stroke. However, the restoration often leads to cerebral ischemia-reperfusion injury (CIR/I), which greatly increases the risk of non-neural organ damage. In particular, the acute kidney injury might be one of the most common complications. Aims: The study aimed to understand the damage occurred and the potential molecular mechanisms. Methods: The study was explored on the CIR/I rats generated by performing middle cerebral artery occlusion/reperfusion (MCAO/Reperfusion). The rats were evaluated with injury on the brains, followed by the non-neural organs including kidneys, livers, colons and stomachs. They were examined further with histopathological changes, and gene expression alterations by using RT-qPCR of ten aquaporins (Aqps) subtypes including Aqp1ï½Aqp9 and Aqp11. Furthermore, the Aqps expression profiles were constructed for each organ and analyzed by performing Principle Component Analysis. In addition, immunohistochemistry was explored to look at the protein expression of Aqp1, Aqp2, Aqp3 and Aqp4 in the rat kidneys. Results: There was a prominent down-regulation profile in the MCAO/Reperfusion rat kidneys. The protein expression of Aqp1, Aqp2, Aqp3 and Aqp4 was decreased in the kidneys of the MCAO/Reperfusion rats. We suggested that the kidney was in the highest risk to be damaged following the CIR/I. Down-regulation of Aqp2, Aqp3 and Aqp4 was involved in the acute kidney injury induced by the CIR/I.