{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:14:12Z","timestamp":1789038852640,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T00:00:00Z","timestamp":1466553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS072966"],"award-info":[{"award-number":["NS072966"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS056093"],"award-info":[{"award-number":["NS056093"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001605","name":"Epilepsy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001605","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2016,8]]},"abstract":"Summary<\/jats:title>Objective<\/jats:title>This study attempted to validate the effects of neonatal estradiol in ameliorating the spasms in the prenatally betamethasone\u2010primed N<\/jats:italic>\u2010methyl\u2010d<\/jats:sc>\u2010aspartate (NMDA<\/jats:styled-content>) model of infantile spasms in rats as shown previously in a mouse Arx<\/jats:italic> gene knock\u2010in expansion model of infantile spasms.<\/jats:p><\/jats:sec>Methods<\/jats:title>Neonatal rats prenatally exposed to betamethasone (on day 15 of pregnancy) were treated with subcutaneous 40 ng\/g estradiol benzoate (EB<\/jats:styled-content>) between postnatal days (P)3\u2013P10 or P0\u2013P5. A synthetic estrogen analogue, diethylstilbestrol, was used between P0 and P5 (2 \u03bcg per rat, s.c.). On P12, P13, and P15, the rats were subjected to NMDA<\/jats:styled-content>\u2010triggered spasms, and latency to onset and number of spasms were evaluated. Rats with EB<\/jats:styled-content> on P3\u2013P10 were tested after spasms in the open field, novel object recognition, and elevated plus maze to determine effects of treatment on behavior. Additional rats with P3\u2013P10 or P0\u2013P5 EB<\/jats:styled-content> were investigated for \u03b3\u2010aminobutyric acid (GABA<\/jats:styled-content>)ergic neurons (glutamate decarboxylase [GAD<\/jats:styled-content>]67 expression) in the neocortex. As a positive control, a group of rats received either subcutaneous adrenocorticotropic hormone (ACTH<\/jats:styled-content>) (2 \u00d7 0.3 mg\/kg on P12 and 3 \u00d7 0.3 mg\/kg on P13 and P14) or vehicle after the first episode of spasms on P12.<\/jats:p><\/jats:sec>Results<\/jats:title>Neither EB<\/jats:styled-content> treatment nor diethylstilbestrol consistently affected expression of spasms in this model, although we found a significant increase in GAD<\/jats:styled-content>67\u2010immunopositive cells in the neocortex after P3\u2013P10 and P0\u2013P5 EB<\/jats:styled-content> treatment, consistent with a study in mice. Behavioral tests showed increase in lateralization in male rats treated with P3\u2013P10 EB<\/jats:styled-content>, a behavioral trait usually associated with female sex. Diethylstilbestrol treatment in male rats resulted in arrested pubertal descent of testes. ACTH<\/jats:styled-content> had robust effects in suppressing spasms.<\/jats:p><\/jats:sec>Significance<\/jats:title>Treatment of infantile spasms (IS<\/jats:styled-content>) using neonatal EB<\/jats:styled-content> may be justified in those cases of IS<\/jats:styled-content> that present with detectable deficits in GABA<\/jats:styled-content>ergic neurons. In other types of IS<\/jats:styled-content>, the efficacy of neonatal EB<\/jats:styled-content> and its analogues is not supported.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13434","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T21:49:20Z","timestamp":1466718560000},"page":"1326-1336","source":"Crossref","is-referenced-by-count":20,"title":["Estradiol does not affect spasms in the betamethasone\u2010NMDA<\/scp> rat model of infantile spasms"],"prefix":"10.1111","volume":"57","author":[{"given":"Tamar","family":"Chachua","sequence":"first","affiliation":[{"name":"Department of Cell Biology & Anatomy New York Medical College Valhalla NY U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Di Grazia","sequence":"additional","affiliation":[{"name":"Department of Cell Biology & Anatomy New York Medical College Valhalla NY 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