{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T18:07:44Z","timestamp":1771870064792,"version":"3.50.1"},"reference-count":0,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Physiol Biochem"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>Background\/Aims: This study was to examine the role played by hypoxia inducible factor-1 (HIF-1\u03b1) in regulating pro-inflammatory cytokines (PICs) pathway in the rat hippocampus after cardiac arrest (CA) induced-transient global ischemia followed by cardiopulmonary resuscitation (CPR). Those PICs include interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6) and tumor necrosis factor-\u03b1 (TNF-\u03b1). Methods: A rat model of CA induced by asphyxia was used in the current study. Following CPR, the hippocampus CA1 region was obtained for ELISA to determine the levels of HIF-1\u03b1 and PICs; and Western Blot analysis to determine the protein levels of PIC receptors. Results: Our data show that IL-1\u03b2, IL-6 and TNF-\u03b1 were significant elevated in the hippocampus after CPR as compared with control group. This was companied with increasing of HIF-1\u03b1 and the time courses for HIF-1\u03b1 and PICs were similar. In addition, PIC receptors, namely IL-1R, IL-6R and TNFR1 were upregulated in CA rats. Also, stimulation of HIF-1\u03b1 by systemic administration of ML228, HIF-1\u03b1 activator, significantly attenuated the amplified IL-6\/IL-6R and TNF-\u03b1 \/TNFR1 pathway in the hippocampus of CA rats, but did not modify IL-1\u03b2 and its receptor. Moreover, ML228 attenuated upregulated expression of Caspase-3 indicating cell apoptosis evoked by CA. Conclusion: Transient global ischemia induced by CA increases the levels of IL-1\u03b2, IL-6 and TNF-\u03b1 and thereby leads to enhancement in their respective receptor in the rat hippocampus. Stabilization of HIF-1\u03b1 plays a role in attenuating amplified expression IL-6R, TNFR1 and Caspase-3 in the processing of transient global ischemia. Results of our study suggest that PICs contribute to cerebral injuries evoked by transient global ischemia and in this pathophysiological process activation of HIF-1\u03b1 improves tissues against ischemic injuries. Our data revealed specific signaling pathways in alleviating CA-evoked global cerebral ischemia by elucidating that HIF-1\u03b1 plays an important role in regulating PIC signal pathways and Caspase-3. The subsequent induction of HIF-1\u03b1 and its target signals is likely a part of the intrinsic neuroprotective effects aimed at attenuating damage as a result of global cerebral ischemia. Thus, targeting one or more of these signaling molecules has clinical implications for treatment and improvement of CA-evoked global cerebral ischemia often observed in clinics.<\/jats:p>","DOI":"10.1159\/000445643","type":"journal-article","created":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T21:03:08Z","timestamp":1467838988000},"page":"511-520","source":"Crossref","is-referenced-by-count":59,"title":["HIF-1\u03b1 Activation Attenuates IL-6 and TNF-\u03b1 Pathways in Hippocampus of Rats Following Transient Global Ischemia"],"prefix":"10.1159","volume":"39","author":[{"given":"Jihong","family":"Xing","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2016,7,7]]},"container-title":["Cellular Physiology and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/445643","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/445643","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/445643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:59:38Z","timestamp":1745431178000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000445643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,7,29]]}},"URL":"https:\/\/doi.org\/10.1159\/000445643","archive":["Portico"],"relation":{},"ISSN":["1015-8987","1421-9778"],"issn-type":[{"value":"1015-8987","type":"print"},{"value":"1421-9778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016]]}}}