{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:59:18Z","timestamp":1792252758109,"version":"4.4.0"},"reference-count":55,"publisher":"SAGE Publications","issue":"21-22","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"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":[[2024,11]]},"abstract":"<jats:p>\n                    Cholinergic disruptions underlie attentional deficits following traumatic brain injury (TBI). Yet, drugs specifically targeting acetylcholinesterase (AChE) inhibition have yielded mixed outcomes. Therefore, we hypothesized that galantamine (GAL), a dual-action competitive AChE inhibitor and \u03b17 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator, provided chronically after injury, will attenuate TBI-induced deficits of sustained attention and enhance ACh efflux in the medial prefrontal cortex (mPFC), as assessed by\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    microdialysis. In Experiment 1, adult male rats (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 10\u201315\/group) trained in the 3-choice serial reaction time (3-CSRT) test were randomly assigned to controlled cortical impact (CCI) or sham surgery and administered GAL (0.5, 2.0, or 5.0 mg\/kg; i.p.) or saline vehicle (VEH; 1 mL\/kg; i.p) beginning 24-h post-surgery and once daily thereafter for 27 days. Measures of sustained attention and distractibility were assessed on post-operative days 21\u201325 in the 3-CSRT, following which cortical lesion volume and basal forebrain cholinergic cells were quantified on day 27. In Experiment 2, adult male rats (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 3\u20134\/group) received a CCI and 24 h later administered (i.p.) one of the three doses of GAL or VEH for 21 days to quantify the dose-dependent effect of GAL on\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    ACh efflux in the mPFC. Two weeks after the CCI, a guide cannula was implanted in the right mPFC. On post-surgery day 21, baseline and post-injection dialysate samples were collected in a temporally matched manner with the cohort undergoing behavior. ACh levels were analyzed using reverse phase high-performance liquid chromatography (HPLC) coupled to an electrochemical detector. Cortical lesion volume was quantified on day 22. The data were subjected to ANOVA, with repeated measures where appropriate, followed by Newman\u2013Keuls\n                    <jats:italic toggle=\"yes\">post hoc<\/jats:italic>\n                    analyses. All TBI groups displayed impaired sustained attention versus the pooled SHAM controls (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2019s &lt; 0.05). Moreover, the highest dose of GAL (5.0 mg\/kg) exacerbated attentional deficits relative to VEH and the two lower doses of GAL (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2019s &lt; 0.05). TBI significantly reduced cholinergic cells in the right basal forebrain, regardless of treatment condition, versus SHAM (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.05).\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    microdialysis revealed no differences in basal ACh in the mPFC; however, GAL (5.0 mg\/kg) significantly increased ACh efflux 30 min following injection compared to the VEH and the other GAL (0.5 and 2.0 mg\/kg) treated groups (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2019s &lt; 0.05). In both experiments, there were no differences in cortical lesion volume across treatment groups (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2019s &gt; 0.05). In summary, albeit the higher dose of GAL increased ACh release, it did not improve measures of sustained attention or histopathological markers, thereby partially supporting the hypothesis and providing the impetus for further investigations into alternative cholinergic pharmacotherapies such as nAChR positive allosteric modulators.\n                  <\/jats:p>","DOI":"10.1089\/neu.2024.0173","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T04:18:34Z","timestamp":1718770714000},"page":"2428-2441","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Evaluating the Efficacy of Chronic Galantamine on Sustained Attention and Cholinergic Neurotransmission in A Pre-Clinical Model of Traumatic Brain Injury"],"prefix":"10.1177","volume":"41","author":[{"given":"Eleni H.","family":"Moschonas","sequence":"first","affiliation":[{"name":"Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley E.","family":"Capeci","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 School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M.","family":"Annas","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 School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica B.","family":"Domyslawski","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 School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade A.","family":"Steber","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 School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey M.","family":"Donald","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 School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R.","family":"Genkinger","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 School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piper L.","family":"Rennerfeldt","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 School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Bittner","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 School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent J.","family":"Vozzella","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 School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, 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