{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T03:53:02Z","timestamp":1752983582790,"version":"3.40.5"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T00:00:00Z","timestamp":1696032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD052664","R01HD083001\u201001A1","U54\u2010HD087011"],"award-info":[{"award-number":["HD052664","R01HD083001\u201001A1","U54\u2010HD087011"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Exposure of neonatal macaques to the antiseizure medications phenobarbital and midazolam (PbM) causes widespread apoptotic death of neurons and oligodendrocytes. We studied behavior and neurocognitive performance in 12 to 24\u2009month\u2010old macaques treated as neonates with PbM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 14 monkeys received phenobarbital and midazolam over 24\u2009hours under normothermia (n\u2009=\u20098) or mild hypothermia (n\u2009=\u20096). Controls (n\u2009=\u20098) received no treatment. Animals underwent testing in the human intruder paradigm at ages 12 and 18\u2009months, and a 3\u2010step stimulus discrimination task at ages 12, 18, and 24\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Animals treated with PbM displayed lower scores for environmental exploration, and higher scores for locomotion and vocalizations compared with controls. Combined PbM and hypothermia resulted in lower scores for aggression and vigilance at 12\u2009months compared with controls and normothermic PbM animals.<\/jats:p><jats:p>A mixed\u2010effects generalized linear model was used to test for differences in neurocognitive performance between the control and PbM groups in the first step of the stimulus discrimination task battery (shape center baited to shape center non\u2010baited). The odds of passing this step differed by group (<jats:italic>p<\/jats:italic>\u2009=\u20090.044). At any given age, the odds of passing for a control animal were 9.53\u2010fold (95% CI 1.06\u201385) the odds for a PbM animal. There was also evidence suggesting a higher learning rate in the shape center non\u2010baited for the control relative to the PbM group (Cox model HR 2.13, 95% CI 1.02\u20134.43; <jats:italic>p<\/jats:italic>\u2009=\u20090.044).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These findings demonstrate that a 24\u2010hour\u2010long neonatal treatment with a clinically relevant combination of antiseizure medications can have long\u2010lasting effects on behavior and cognition in nonhuman primates. ANN NEUROL 2024;95:57\u201370<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.26794","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T16:44:49Z","timestamp":1694709889000},"page":"57-70","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Behavioral and Cognitive Outcomes of Rhesus Macaques Following Neonatal Exposure to Antiseizure Medications"],"prefix":"10.1002","volume":"95","author":[{"given":"Ricki","family":"Colman","sequence":"first","affiliation":[{"name":"Wisconsin National Primate Research Center  Madison WI USA"},{"name":"Department of Cell and Regenerative Biology University of Wisconsin, School of Medicine  Madison WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Pierre","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center  Madison WI 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