{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:05:00Z","timestamp":1780909500150,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Malformations of cortical development (MCD), a major cause of early\u2010onset epilepsy, arise from disruptions in fetal corticogenesis, suggesting that prenatal intervention may be required to alter their developmental trajectory. Insulin\u2010like growth factor\u20101 (IGF\u20101) has been proposed as a potential therapeutic agent due to its roles in neuronal survival, synaptogenesis, and plasticity. However, whether prenatal or prolonged early\u2010life IGF\u20101 exposure can modify the trajectory of malformed cortical circuits remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Pregnant dams were exposed to MAM to induce cortical malformation, and fetal brain development was assessed at embryonic day 19 (E19) using in utero MRI. Offspring were assigned to receive prenatal and\/or prolonged early postnatal administration of the truncated IGF\u20101 analog (1\u20133)IGF\u20101. Outcomes after IGF\u20101 treatment were evaluated across multiple domains, including brain morphology, body growth, seizure susceptibility, neurometabolic profiles (\n                      <jats:sup>1<\/jats:sup>\n                      H\u2010MRS), and behavioral performance (Y\u2010maze, open field, fear conditioning).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fetal MRI revealed significantly reduced brain size in MAM\u2010exposed fetuses, indicating that structural abnormalities were already established prenatally. Neither prenatal nor prolonged postnatal (1\u20133)IGF\u20101 treatment improved whole\u2010brain growth, neurometabolite levels, or susceptibility to N\u2010methyl\u2010D\u2010aspartate\u2010induced spasms. Moreover, long\u2010term IGF\u20101 exposure led to adverse behavioral outcomes, including impaired spatial working memory in the Y\u2010maze and increased freezing during conditioning, without affecting locomotor activity or fear recall. No beneficial effects were observed across any treatment paradigm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although IGF\u20101 has known neurotrophic properties, early and sustained exposure to the (1\u20133)IGF\u20101 analog did not ameliorate structural\u2010, metabolic\u2010, or seizure\u2010related abnormalities and produced detrimental behavioral effects in this model of cortical malformation. These findings underscore the importance of developmental timing and molecular specificity when applying IGF\u20101\u2010based interventions and caution against the assumption that earlier or prolonged treatment is necessarily beneficial in malformed cortical circuits.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71405","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:57:57Z","timestamp":1776409077000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal (1\u20133)IGF\u20101 Treatment Is Ineffective and Behaviorally Detrimental in a Rat Model of Cortical Malformation"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6636-6054","authenticated-orcid":false,"given":"Minyoung","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Ulsan College of Medicine  Seoul South Korea"},{"name":"Asan Institute for Life Sciences, Asan Medical Center  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8049-5901","authenticated-orcid":false,"given":"Eun\u2010Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Ulsan College of Medicine  Seoul South Korea"},{"name":"Asan Institute for Life Sciences, Asan Medical Center  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-5258","authenticated-orcid":false,"given":"Mi\u2010Sun","family":"Yum","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Ulsan College of Medicine  Seoul South Korea"},{"name":"Department of Pediatrics Asan Medical Center Children's Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887\u2010024\u201004526\u20103"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/jme\u201017\u20100254"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2201\/nonlin.003.01.002"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26383"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2007.01.014"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21609"},{"issue":"2","key":"e_1_2_11_8_1","first-page":"145","article-title":"Insulin\u2010Like Growth Factors and Brain Development","volume":"233","author":"D'Ercole A. 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