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The amount of apoptotic neurons was determined using <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content> assay. The expressions of Bcl\u20102, Bax, Akt, <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2, <jats:styled-content style=\"fixed-case\">IKK<\/jats:styled-content><jats:italic>\u03b2<\/jats:italic>, I<jats:italic>\u03ba<\/jats:italic>B<jats:italic>\u03b1<\/jats:italic> were measured using Western blot. The nuclear translocation and activation of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B was measured using a fluorescence microscope and electrophoretic mobility shift assay (<jats:styled-content style=\"fixed-case\">EMSA<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bakkenolide\u2010IIIa (4, 8, 16 mg\/kg; i.g.) was administered immediately after reperfusion could reduce the brain infarct volume, and the neurological deficit, as well as a high dose of bakkenolide\u2010IIIa, increases the 72 h survival rate in cerebrally damaged rats. <jats:italic>In vitro<\/jats:italic> data demonstrated that bakkenolide\u2010IIIa could increase cell viability and decrease the amount of apoptotic cells in cultured primary hippocampal neurons exposed to <jats:styled-content style=\"fixed-case\">OGD<\/jats:styled-content>. Bakkenolide\u2010IIIa also dose\u2010dependently increased the ratio of Bcl\u20102 to Bax. These results indicated that inhibition of apoptosis partly mediated the neuroprotection of bakkenolide\u2010IIIa. Furthermore, bakkenolide\u2010IIIa inhibited the phosphorylation of Akt, <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2, <jats:styled-content style=\"fixed-case\">IKK<\/jats:styled-content><jats:italic>\u03b2<\/jats:italic>, I<jats:italic>\u03ba<\/jats:italic>B<jats:italic>\u03b1<\/jats:italic>, and p65 in cultured hippocampal neurons exposed to <jats:styled-content style=\"fixed-case\">OGD<\/jats:styled-content>. Bakkenolide\u2010IIIa not only inhibited the nuclear translocation of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B in cultured neurons exposed to <jats:styled-content style=\"fixed-case\">OGD<\/jats:styled-content>, but also inhibited the activation of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B in peri\u2010infarct area in cerebrally damaged rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, our findings indicated that bakkenolide\u2010IIIa protects against cerebral damage by inhibiting <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 activation and inactivated <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B signaling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12470","type":"journal-article","created":{"date-parts":[[2015,10,29]],"date-time":"2015-10-29T04:48:50Z","timestamp":1446094130000},"page":"943-952","source":"Crossref","is-referenced-by-count":7,"title":["Bakkenolide\u2010IIIa Protects Against Cerebral Damage Via Inhibiting <scp>NF<\/scp>\u2010<i>\u03ba<\/i>B Activation"],"prefix":"10.1111","volume":"21","author":[{"given":"Qian","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy College of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Run\u2010Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Diving Medicine Faculty of Naval Medicine Second Military Medical University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of 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