{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:29:33Z","timestamp":1791430173157,"version":"4.3.3"},"reference-count":77,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1176426"],"award-info":[{"award-number":["APP1176426"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Valproic acid (VPA) is a first\u2010line antiseizure medication (ASM) that is highly efficacious for treating generalized and focal epilepsy disorders. Unfortunately, due to its strong association with teratogenic effects culminating in fetal valproate spectrum disorder (FVSD), which may include neurocognitive and neurobehavioral deficits, the drug has become highly regulated\/restricted for women of childbearing potential. This includes those who have been shown to respond well to the drug and respond poorly to alternative ASMs. Concurrently, VPA's neurotoxic, teratogenic mechanisms have been studied in\u00a0vitro, and continued research may aid in providing depth to our understanding so that superior evidence\u2010based care plans and novel drug designs can be made for patients with epilepsy disorders. This scoping review systematically assesses what in\u00a0vitro studies have discovered regarding VPA's effects on neural cells and the proposed cellular neurotoxic mechanisms. Neurotoxicity studies have captured the cytotoxic, dysmorphological, genetic, and epigenetic effects in murine and human primary, immortalized, and stem cells in\u00a0vitro. This includes extensive identification of many genes and gene pathways associated with neurodevelopmental disorders, a hallmark of FVSD. Although published studies have illuminated much about VPA's neurotoxic, teratogenic effects, a lack of standardization in testing methodologies renders making direct comparisons between the results of different studies challenging. Nevertheless, the recent use of human stem cell\u2010based models provides a richer understanding of what cellular, molecular, genetic, and epigenetic effects are caused by VPA exposure. Future in\u00a0vitro studies may improve their clinical translatability by administering clinically relevant concentrations of VPA to human stem cell\u2010derived neural cells and fostering a better understanding of VPA's neural cell type\u2010specific and epigenetic effects. In\u00a0vitro VPA neurotoxicity studies on neurodevelopment show a clear potential to provide data that may help construct superior personalized evidence\u2010based treatment plans and novel drug designs for women of childbearing potential with epilepsy disorders.<\/jats:p>","DOI":"10.1111\/epi.18392","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T19:27:59Z","timestamp":1743362879000},"page":"2170-2181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["In vitro models of valproic acid to assess neurodevelopmental toxicity: A scoping review"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1601-4057","authenticated-orcid":false,"given":"Daniel","family":"Sandvik","sequence":"first","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine Monash University  Melbourne Victoria 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