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Cellular damage post insult occurs after a delay and is mediated by a secondary neural energy failure. <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\u2010activated protein kinase (<jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>) is a sensor of cellular stress resulting from <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> depletion and\/or calcium dysregulation, hallmarks of the neuronal cell death observed after <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activation has been implicated in the models of adult ischaemic injury but, as yet, there have been no studies defining its role in neonatal asphyxia. Here, we find that in an\u00a0<jats:italic>in vivo<\/jats:italic> model of neonatal hypoxia\u2013ischaemic and in oxygen\/glucose deprivation in neurons, there is pathological activation\u00a0of the calcium\/calmodulin\u2010dependent protein kinase kinase \u03b2 (CaMKK\u03b2)\u2010<jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>\u03b11 signalling pathway. Pharmacological inhibition of <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> during the insult promotes neuronal survival but, conversely, inhibiting <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activity prior to the insult sensitizes neurons, exacerbating cell death. Our data have pathological relevance for neonatal <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content> as prior sensitization such as exposure to bacterial infection (reported to reduce <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activity) produces a significant increase in injury.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13034-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>We show that in an <jats:italic>in vivo<\/jats:italic> model of neonatal hypoxia\u2013ischaemic and in oxygen\/glucose deprivation in neurons, there is a pathological activation of the CaMKK\u03b2\u2010AMPK\u03b11 signalling pathway. Inhibiting AMPK during OGD promotes neuronal survival; conversely, inhibiting AMPK prior to OGD exacerbates cell death. Our data have clinical relevance as\u00a0prior sensitization (e.g. exposure to bacterial infection reducing AMPK activity) increases injury. AMPK, AMP\u2010activated protein kinase; HI, hypoxia\u2013ischaemia; OGD, oxygen\u2013glucose deprivation.<\/jats:p>","DOI":"10.1111\/jnc.13034","type":"journal-article","created":{"date-parts":[[2015,1,17]],"date-time":"2015-01-17T06:25:11Z","timestamp":1421475911000},"page":"242-252","source":"Crossref","is-referenced-by-count":54,"title":["A dual role for <scp>AMP<\/scp>\u2010activated protein kinase (AMPK) during neonatal hypoxic\u2013ischaemic brain injury in mice"],"prefix":"10.1111","volume":"133","author":[{"given":"Catherine I.","family":"Rousset","sequence":"first","affiliation":[{"name":"Division of Imaging Sciences and Biomedical Engineering Centre for the Developing Brain King's College London King's Health Partners St. Thomas\u2019 Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona C.","family":"Leiper","sequence":"additional","affiliation":[{"name":"Redox Metabolism Group MRC Clinical Sciences Centre Imperial College London 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