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As energy availability after <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> is suppressed, we questioned if increasing <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activity after <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> would improve cognitive outcome. <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> was delivered using the electromagnetic controlled cortical impact model on male Sprague\u2013Dawley rats (275\u2013300\u00a0g) and C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice (20\u201325\u00a0g). <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activity within the injured parietal cortex and ipsilateral hippocampus was inferred by western blots using phospho\u2010specific antibodies. The consequences of acute manipulation of <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> signaling on cognitive function were assessed using the Morris water maze task. We found that <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activity is decreased as a result of injury, as indicated by reduced <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> phosphorylation and corresponding changes in the phosphorylation of its downstream targets: ribosomal protein S6 and Akt Substrate of 160\u00a0<jats:styled-content style=\"fixed-case\">kD<\/jats:styled-content>a (<jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>160). Increasing <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activity after injury using the drugs 5\u2010amino\u20101\u2010\u03b2\u2010<jats:sc>d<\/jats:sc>\u2010ribofuranosyl\u2010imidazole\u20104\u2010carboxamide or metformin did not affect spatial learning, but significantly improved spatial memory. Taken together, our results suggest that decreased <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activity after <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> may contribute to the cellular energy crisis in the injured brain, and that <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activators may have therapeutic utility.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\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\/jnc13726-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nIncreased phosphorylation of Thr172 activates AMP\u2010activated protein kinase (AMPK) under conditions of low cellular energy availability. This leads to inhibition of energy consuming, while activating energy generating, processes. Hill <jats:italic>et\u00a0al<\/jats:italic>., present data to indicate that TBI decreases Thr172 phosphorylation and that its stimulation by pharmacological agents offers neuroprotection and improves memory. These results suggest that decreased AMPK phosphorylation after TBI incorrectly signals the injured brain that excess energy is available, thereby contributing to the cellular energy crisis and memory impairments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13726","type":"journal-article","created":{"date-parts":[[2016,7,5]],"date-time":"2016-07-05T15:59:14Z","timestamp":1467734354000},"page":"106-119","source":"Crossref","is-referenced-by-count":64,"title":["Traumatic brain injury decreases <scp>AMP<\/scp>\u2010activated protein kinase activity and pharmacological enhancement of its activity improves cognitive outcome"],"prefix":"10.1111","volume":"139","author":[{"given":"Julia L.","family":"Hill","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Anatomy McGovern Medical School Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhide","family":"Kobori","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy McGovern Medical School Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy McGovern Medical School Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia S.","family":"Rozas","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy McGovern Medical School Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Hylin","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy McGovern Medical School Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony N.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy McGovern Medical School Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramod K.","family":"Dash","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy McGovern Medical School Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2011.2067"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.07.006"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-014-9632-2"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600301"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csm.2010.09.001"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-09-03535.1999"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-1-57"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106554"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2012.12.020"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:17:1:45"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00277-4"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011383"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024648"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21628"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1994.11.629"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(91)90104-8"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(94)90360-3"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.9.1963"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.09.018"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2008.0771"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21677"},{"key":"e_1_2_7_23_1","first-page":"228","article-title":"The neurometabolic cascade of concussion","volume":"36","author":"Giza C. 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