Abstract
This study was carried out to investigate the exact mechanisms behind the neuroprotective effects of oleoylethanolamide (OEA) after acute cerebral ischemic injury. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. OEA (40 mg/kg, ip) was administered with a single injection upon reperfusion. The number of apoptotic cells was detected by TUNEL staining. The expression of Bax, Bcl-2, and TLR4, as well as the activities of NF-κB, Akt, and ERK1/2 were analyzed by western blot. Our data showed that OEA treatment alleviated cell apoptosis in a mouse model of ischemic stroke, accompanied by suppression of Bax, as well as upregulation of antiapoptotic protein Bcl-2 level. The changes of Bax and Bcl-2 could not be observed in PPARα knockout mice models with OEA administration. Importantly, OEA inhibited MCAO-induced TLR4 expression, NF-κB activation, IκBα degradation, and ERK1/2 phosphorylation. Our findings demonstrated that the neuroprotective effects of OEA on cerebral ischemia may be attributed to its antiapoptotic property achieved, at least in part, through the PPARα signaling and inhibition of both TLR4/NF-κB and ERK1/2 signaling pathways. These results provide new evidence indicating the neuroprotective effect of OEA on ischemic stroke.
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Acknowledgments
This study was supported by grants from the National Natural Sciences Foundation of China (Nos. 81373407, 81402921, and 81603093), the Natural Science Foundation of Fujian, China (Nos. 2016J01415, 2016D024, and 2015J01354), and the Science and Technology Project of Xiamen, China (No. 3502Z20144027).
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Hao Zhou, Wu-shuang Yang, and Ying Li contributed equally to this work and should be considered co-first authors.
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Zhou, H., Yang, Ws., Li, Y. et al. Oleoylethanolamide attenuates apoptosis by inhibiting the TLR4/NF-κB and ERK1/2 signaling pathways in mice with acute ischemic stroke. Naunyn-Schmiedeberg's Arch Pharmacol 390, 77–84 (2017). https://doi.org/10.1007/s00210-016-1309-4
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DOI: https://doi.org/10.1007/s00210-016-1309-4