{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:00:39Z","timestamp":1791388839867,"version":"4.3.3"},"reference-count":71,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"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":["Neurotrauma Reports"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>\n                    <jats:bold>Abstract<\/jats:bold>\n                  <\/jats:title>\n                  <jats:p>\n                    Many military veterans who experienced blast-related traumatic brain injuries (TBIs) in the conflicts in Iraq and Afghanistan suffer from chronic cognitive and mental health problems, including post-traumatic stress disorder (PTSD). Male rats subjected to repetitive low-level blast exposure develop chronic cognitive and PTSD-related traits that develop in a delayed manner. Ketamine has received attention as a treatment for refractory depression and PTSD. (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] is a ketamine metabolite that exerts rapid antidepressant actions. (2R,6R)-HNK has become of clinical interest because of its favorable side-effect profile, low abuse potential, and oral route of administration. We treated three cohorts of blast-exposed rats with (2R,6R)-HNK, beginning 7\u201311 months after blast exposure, a time when the behavioral phenotype is established. Each cohort consisted of groups (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200910\u201313\/group) as follows: 1) Sham-exposed treated with saline, 2) blast-exposed treated with saline, and 3) blast-exposed treated with a single dose of 20\u2009mg\/kg of (2R,6R)-HNK. (2R,6R)-HNK rescued blast-induced deficits in novel object recognition (NOR) and anxiety-related features in the elevated zero maze (EZM) in all three cohorts. Exaggerated acoustic startle was reversed in cohort 1, but not in cohort 3. (2R,6R)-HNK effects were still present in the EZM 12 days after administration in cohort 1 and 27 days after administration in NOR testing of cohorts 2 and 3. (2R,6R)-HNK may be beneficial for the neurobehavioral syndromes that follow blast exposure in military veterans. Additional studies will be needed to determine whether higher doses or more extended treatment regimens may be more effective.\n                  <\/jats:p>","DOI":"10.1089\/neur.2022.0088","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T08:55:27Z","timestamp":1680252927000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["(2R,6R)-Hydroxynorketamine Treatment of Rats Exposed to Repetitive Low-Level Blast Injury"],"prefix":"10.1177","volume":"4","author":[{"given":"Georgina Perez","family":"Garcia","sequence":"first","affiliation":[{"name":"Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA."},{"name":"Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gissel M.","family":"Perez","sequence":"additional","affiliation":[{"name":"Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita De","family":"Gasperi","sequence":"additional","affiliation":[{"name":"Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA."},{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A. Gama","family":"Sosa","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"General Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Otero-Pagan","sequence":"additional","affiliation":[{"name":"Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Abutarboush","sequence":"additional","affiliation":[{"name":"Department of Neurotrauma, Naval Medical Research Center, Silver Spring, Maryland, USA."},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usmah","family":"Kawoos","sequence":"additional","affiliation":[{"name":"Department of Neurotrauma, Naval Medical Research Center, Silver Spring, Maryland, USA."},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan K.","family":"Statz","sequence":"additional","affiliation":[{"name":"Department of Neurotrauma, Naval Medical Research Center, Silver Spring, Maryland, USA."},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Neurotrauma, Naval Medical Research Center, Silver Spring, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn W.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA."},{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Department of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick R.","family":"Hof","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Department of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Cook","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington, USA."},{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T.","family":"Ahlers","sequence":"additional","affiliation":[{"name":"Department of Neurotrauma, Naval Medical Research Center, Silver Spring, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Elder","sequence":"additional","affiliation":[{"name":"Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA."},{"name":"Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134294"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa072972"},{"key":"e_1_3_5_4_2","doi-asserted-by":"crossref","unstructured":"Tanielian T Jaycox LH (eds). Invisible Wounds of War: Psychological and Cognitive Injuries Their Consequences and Services to Assist Recovery. Rand Corporation: Santa Monica CA; 2008.","DOI":"10.1037\/e527612010-001"},{"key":"e_1_3_5_5_2","doi-asserted-by":"crossref","unstructured":"Engel C Hoch E Simmons M. 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