{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:26:19Z","timestamp":1789748779857,"version":"4.0.1"},"reference-count":41,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>\n                    Although the mechanisms that contribute to the development of traumatic brain injury (TBI)-related deficits are not fully understood, it has been proposed that altered energy utilization may be a contributing factor. The tuberous sclerosis complex, a heterodimer composed of hamartin\/Tsc-1 and tuberin\/Tsc-2, is a critical regulatory node that integrates nutritional and growth signals to govern energy using processes by regulating the activity of mechanistic Target of Rapamycin complex 1 (mTORC1). mTORC1 activation results in enhanced protein synthesis, an energy consuming process. We show that mice that have a heterozygous deletion of\n                    <jats:italic toggle=\"yes\">Tsc2<\/jats:italic>\n                    exhibit elevated basal mTORC1 activity in the cortex and the hippocampus while still exhibiting normal motor and neurocognitive functions. In addition, a mild closed head injury (mCHI) that did not activate mTORC1 in wild-type mice resulted in a further increase in mTORC1 activity in\n                    <jats:italic toggle=\"yes\">\n                      Tsc2\n                      <jats:sup>+\/KO<\/jats:sup>\n                    <\/jats:italic>\n                    mice above the level of activity observed in uninjured\n                    <jats:italic toggle=\"yes\">\n                      Tsc2\n                      <jats:sup>+\/KO<\/jats:sup>\n                    <\/jats:italic>\n                    mice. This enhanced level of increased mTORC1 activity was associated with worsened cognitive function as assessed using the Morris water maze and context discrimination tasks. These results suggest that there is a threshold of increased mTORC1 activity after a TBI that is detrimental to neurobehavioral performance, and interventions to inhibit excessive mTORC1 activation may be beneficial to neurocognitive outcome.\n                  <\/jats:p>","DOI":"10.1089\/neu.2014.3469","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T12:39:59Z","timestamp":1405427999000},"page":"149-158","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Genetic Activation of mTORC1 Signaling Worsens Neurocognitive Outcome after Traumatic Brain Injury"],"prefix":"10.1177","volume":"32","author":[{"given":"Natalia S.","family":"Rozas","sequence":"first","affiliation":[{"name":"the University of Texas Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Redell","sequence":"additional","affiliation":[{"name":"the University of Texas Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia L.","family":"Hill","sequence":"additional","affiliation":[{"name":"the University of Texas Medical School"},{"name":"Lieber Institute for Brain Development"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"James","family":"McKenna","sequence":"additional","affiliation":[{"name":"Emory University","place":["Georgia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony N.","family":"Moore","sequence":"additional","affiliation":[{"name":"the University of Texas Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Gambello","sequence":"additional","affiliation":[{"name":"Emory University","place":["Georgia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramod K.","family":"Dash","sequence":"additional","affiliation":[{"name":"the University of Texas Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,1,15]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.9.1963"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2005.22.733"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csm.2010.09.001"},{"key":"e_1_3_3_5_2","first-page":"H2859","article-title":"Uncoupling of local cerebral glucose metabolism and blood flow after acute fluid-percussion injury in rats","volume":"272","author":"Ginsberg M.D.","year":"1997","unstructured":"Ginsberg M.D., , Zhao W., , Alonso O.F., , Loor-Estades J.Y., , Dietrich W.D., , and Busto R. 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