{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:42:20Z","timestamp":1777927340255,"version":"3.51.4"},"reference-count":91,"publisher":"SAGE Publications","issue":"1-2","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"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":[[2023,1]]},"abstract":"<jats:p>\n                    Traumatic brain injuries (TBIs) affect more than 10 million patients annually worldwide, causing long-term cognitive and psychosocial impairments. Frontal lobe TBIs commonly impair executive function, but laboratory models typically focus primarily on spatial learning and declarative memory. We implemented a multi-modal approach for clinically relevant cognitive-behavioral assessments of frontal lobe function in rats with TBI and assessed treatment benefits of the serotonin-norepinephrine reuptake inhibitor, milnacipran (MLN). Two attentional set-shifting tasks (AST) evaluated cognitive flexibility via the rats' ability to locate food-based rewards by learning, unlearning, and relearning sequential rule sets with shifting salient cues. Adult male rats reached stable pre-injury operant AST (oAST) performance in 3\u20134 weeks, then were isoflurane-anesthetized, subjected to a unilateral frontal lobe controlled cortical impact (2.4\u2009mm depth, 4\u2009m\/sec velocity) or Sham injury, and randomized to treatment conditions. Milnacipran (30\u2009mg\/kg\/day) or vehicle (VEH; 10% ethanol in saline) was administered intraperitoneally via implanted osmotic minipumps (continuous infusions post-surgery, 60\u2009\u03bcL\/h). Rats had a 10-day recovery post-TBI\/Sham before performing light\/location-based oAST for 10 days and, subsequently, odor\/media-based digging AST (dAST) on the last test day (26-27 days post-injury) before sacrifice. Both AST tests revealed significant deficits in TBI+VEH rats, seen as elevated total trials and errors (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.05), which generally normalized in MLN-treated rats (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.05). This first simultaneous dual AST assessment demonstrates oAST and dAST are sufficiently sensitive and robust to detect subtle attentional and cognitive flexibility executive impairments after frontal lobe TBI in rats. Chronic MLN administration shows promise for attenuation of post-TBI executive function deficits, thus meriting further investigation.\n                  <\/jats:p>","DOI":"10.1089\/neu.2022.0289","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T05:38:54Z","timestamp":1660801134000},"page":"112-124","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Milnacipran Ameliorates Executive Function Impairments following Frontal Lobe Traumatic Brain Injury in Male Rats: A Multimodal Behavioral Assessment"],"prefix":"10.1177","volume":"40","author":[{"given":"Timothy J.","family":"Craine","sequence":"first","affiliation":[{"name":"Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"University of Bath, Claverton Down, Bath, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas 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and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine O.","family":"Grobengeiser","sequence":"additional","affiliation":[{"name":"Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian P.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor N.","family":"Magdelinic","sequence":"additional","affiliation":[{"name":"Safar Center for Resuscitation Research, 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