Prenatal Exposure to Corticosteroids Alters Postnatal Susceptibility to Seizures.
Abstract number :
3.013
Submission category :
Year :
2001
Submission ID :
2312
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
L. Velisek, MD, PhD, Neurology & Neuroscience, Albert Einstein College of Medicine, Bronx, NY
RATIONALE: Corticosteroid therapy during the third trimester of pregnancy has been widely used to decrease neonatal mortality and to prevent respiratory distress syndrome. However, repeated administration of corticosteroids during the third trimester of pregnancy coincides with the period of hippocampal neuronal development. In humans, serious maternal stress associated with increases in corticosteroid levels impairs neurological function and behavior in children.Therefore, the effects of repeated prenatal corticosteroid administration on postnatal seizure susceptibility were studied in developing rats.
METHODS: Pregnant rats (Sprague-Dawley, Taconic Farms) were injected with two doses of hydrocortisone (2x10 mg/kg i.p.) 10 hours apart on day 15 of pregnancy (E15). Control pregnant rats received corresponding volumes of saline. The offspring were tested postnatally for susceptibility to kainic acid (3.5 or 5.0 mg/kg i.p.) and flurothyl-induced seizures on postnatal day (PN) 15 and to horizontal bar walking on PN15 and PN17.
RESULTS: Exposure to 2x 10 mg/kg of hydrocortisone on E15 significantly increased the susceptibility to the first KA-induced (5.0 mg/kg) automatisms and to KA-induced status epilepticus in terms of decreased latency to onset in hydrocortisone-exposed rats compared to saline exposed rats. However, there were no effects on seizures induced by the lower dose of KA (3.5 mg/kg) or flurothyl. Prenatal exposure to 2x 10 mg/kg of hydorcortisone did not affect the performance of PN15 rats on the horizontal bar. However, this exposure primed the rats for the deteriorating effects of postnatal seizures. Thus, the rats retested on PN17 after a seizure challenge had a significnatly worse performance than controls.
CONCLUSIONS: Repeated prenatal administration of hydrocortisone on E15 increases susceptibility of the offspring to kainic acid seizures. If the prenatal treatment did not induce alterations in seizure susceptibility per se, there was a synergistic action of prenatal hydrocortisone treatment and seizures on motor performance supporting the [dsquote]two-hit[dsquote] hypothesis.
Support: Supported by NS-20253.