title: Estradiol does not affect spasms in the betamethasone-NMDA rat model of infantile spasms.
abstract: This study attempted to validate the effects of neonatal estradiol in ameliorating the spasms in the prenatally betamethasone-primed N-methyl-d-aspartate (NMDA) model of infantile spasms in rats as shown previously in a mouse Arx gene knock-in expansion model of infantile spasms.
  
  
  
  Neonatal rats prenatally exposed to betamethasone (on day 15 of pregnancy) were treated with subcutaneous 40 ng/g estradiol benzoate (EB) between postnatal days (P)3-P10 or P0-P5. A synthetic estrogen analogue, diethylstilbestrol, was used between P0 and P5 (2 μg per rat, s.c.). On P12, P13, and P15, the rats were subjected to NMDA-triggered spasms, and latency to onset and number of spasms were evaluated. Rats with EB on P3-P10 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-P10 or P0-P5 EB were investigated for γ-aminobutyric acid (GABA)ergic neurons (glutamate decarboxylase [GAD]67 expression) in the neocortex. As a positive control, a group of rats received either subcutaneous adrenocorticotropic hormone (ACTH) (2 × 0.3 mg/kg on P12 and 3 × 0.3 mg/kg on P13 and P14) or vehicle after the first episode of spasms on P12.
  
  
  
  Neither EB treatment nor diethylstilbestrol consistently affected expression of spasms in this model, although we found a significant increase in GAD67-immunopositive cells in the neocortex after P3-P10 and P0-P5 EB treatment, consistent with a study in mice. Behavioral tests showed increase in lateralization in male rats treated with P3-P10 EB, a behavioral trait usually associated with female sex. Diethylstilbestrol treatment in male rats resulted in arrested pubertal descent of testes. ACTH had robust effects in suppressing spasms.
  
  
  
  Treatment of infantile spasms (IS) using neonatal EB may be justified in those cases of IS that present with detectable deficits in GABAergic neurons. In other types of IS, the efficacy of neonatal EB and its analogues is not supported.
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Tamar
authors.initials: T
authors.lastname: Chachua
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Paola
authors.initials: P
authors.lastname: Di Grazia
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Chian-Ru
authors.initials: CR
authors.lastname: Chern
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Meenu
authors.initials: M
authors.lastname: Johnkutty
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hellman
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Ho An
authors.initials: HA
authors.lastname: Lau
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Faariah
authors.initials: F
authors.lastname: Shakil
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Margaret
authors.initials: M
authors.lastname: Daniel
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Cezar
authors.initials: C
authors.lastname: Goletiani
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.|Department of Obstetrics & Gynecology, New York Medical College, Valhalla, NY, U.S.A.|Department of Neurology, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Jana
authors.initials: J
authors.lastname: Velíšková
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, U.S.A.|Department of Neurology, New York Medical College, Valhalla, NY, U.S.A.|Department of Pediatrics, New York Medical College, Valhalla, NY, U.S.A.
authors.forename: Libor
authors.initials: L
authors.lastname: Velíšek
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000627:therapeutic use; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001623:Betamethasone / Q000009:adverse effects*; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D018782:Maze Learning / Q000502:physiology; D019579:Neocortex / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology; D013036:Spasms, Infantile / Q000139:chemically induced* / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents; C074283:estradiol 3-benzoate; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D001623:Betamethasone; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: ACTH; Behavior; Diethylstilbestrol; Epileptic spasms; Validation