title: Validation of the rat model of cryptogenic infantile spasms.
abstract: OBJECTIVE
  To determine whether a new model of cryptogenic infantile spasms consisting of prenatal priming with betamethasone and postnatal trigger of spasms by N-methyl-D-aspartate (NMDA) responds to chronic adrenocorticotropic hormone (ACTH) treatment, and has electroencephalography (EEG) signature, efficacy of treatments, and behavioral impairments similar to those in human infantile spasms.
  
  
  METHODS
  Rats prenatally primed with betamethasone on gestational day 15 were used. Spasms were triggered with NMDA between postnatal days (P) 10 and 15 in a single session or in multiple sessions in one subject. The expression of spasms was compared to prenatally saline-injected controls. Effects of relevant treatments (ACTH, vigabatrin, methylprednisolone, rapamycin) were determined in betamethasone-primed rats. In the rats after spasms, behavioral evaluation was performed in the open field and elevated plus maze on P20-22.
  
  
  RESULTS
  NMDA at P10-15 (the rat "infant" period) triggers the spasms significantly earlier and in greater numbers in the prenatal betamethasone-exposed brain compared to controls. Similar to human condition, the spasms occur in clusters. Repeated trigger of spasms is associated with ictal EEG electrodecrements and interictal large-amplitude waves, a possible rat variant of hypsarrhythmia. Chronic ACTH treatment in a randomized experiment, and chronic pretreatment with methylprednisolone significantly suppress the number of spasms similar to the human condition. Pretreatment with vigabatrin, but not rapamycin, suppressed the spasms. Significant behavioral changes occurred following multiple bouts of spasms.
  
  
  CONCLUSIONS
  The model of infantile spasms has remarkable similarities with the human condition in semiology, EEG, pharmacologic response, and long-term outcome. Therefore, the model can be used to search for novel and more effective treatments for infantile spasms.
authors.affiliation: Department of Neurology, Albert Einstein College of Medicine Einstein/Montefiore Comprehensive Epilepsy Center, Bronx, New York, USA.
authors.forename: Tamar
authors.initials: T
authors.lastname: Chachua
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Yum
authors.forename: Jana
authors.initials: J
authors.lastname: Velíšková
authors.forename: Libor
authors.initials: L
authors.lastname: Velíšek
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D001623:Betamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004569:Electroencephalography; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D018682:GABA Agents / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008775:Methylprednisolone / Q000627:therapeutic use; D016202:N-Methylaspartate / Q000009:adverse effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D013036:Spasms, Infantile / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy*; D013997:Time Factors; D020888:Vigabatrin / Q000627:therapeutic use
chemical_list: D018682:GABA Agents; D005938:Glucocorticoids; D016202:N-Methylaspartate; D000324:Adrenocorticotropic Hormone; D001623:Betamethasone; D020888:Vigabatrin; D008775:Methylprednisolone