{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:39:16Z","timestamp":1785386356858,"version":"3.55.0"},"reference-count":76,"publisher":"Canadian Science Publishing","issue":"9","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:p> Neuroinflammation plays a critical role during sepsis triggered by microglial activation. Mammalian target of rapamycin (mTOR) has gained attraction in neuroinflammation, however, the mechanism remains unclear. Our goal was to assess the effects of mTOR inhibition by rapamycin on inflammation, microglial activation, oxidative stress, and apoptosis associated with the changes in the inhibitor-\u03baB (I\u03baB)-\u03b1\/nuclear factor-\u03baB (NF-\u03baB)\/hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) pathway activity following a systemic challenge with lipopolysaccharide (LPS). Rats received saline (10 mL\/kg), LPS (10\u00a0mg\/kg), and (or) rapamycin (1\u00a0mg\/kg) intraperitoneally. Inhibition of mTOR by rapamycin blocked phosphorylated form of ribosomal protein S6, NF-\u03baB p65 activity by increasing degradation of I\u03baB-\u03b1 in parallel with HIF-1\u03b1 expression increased by LPS in the kidney, heart, lung, and brain tissues. Rapamycin attenuated the increment in the expression of tumor necrosis factor-\u03b1 and interleukin-1\u03b2, the inducible nitric oxide synthase, gp91<jats:sup>phox<\/jats:sup>, and p47<jats:sup>phox<\/jats:sup> in addition to nitrite levels elicited by LPS in tissues or sera. Concomitantly, rapamycin treatment reduced microglial activation, brain expression of caspase-3, and Bcl-2-associated X protein while it increased expression of B cell lymphoma 2 induced by LPS. Overall, this study supports the hypothesis that mTOR contributes to the detrimental effect of LPS-induced systemic inflammatory response associated with neuroinflammation via I\u03baB-\u03b1\/NF-\u03baB\/HIF-1\u03b1 signaling pathway. <\/jats:p>","DOI":"10.1139\/cjpp-2020-0487","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T21:36:45Z","timestamp":1614461805000},"page":"921-934","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["mTOR inhibition as a possible pharmacological target in the management of systemic inflammatory response and associated neuroinflammation by lipopolysaccharide challenge in rats"],"prefix":"10.1139","volume":"99","author":[{"given":"Demet Sinem","family":"Guden","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Mersin University, Mersin, 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