Prenatal corticosteroid exposure alters early developmental seizures and behavior.
Prenatal corticosteroid exposure alters early developmental seizures and behavior.
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DOI：
10.1016/j.eplepsyres.2011.01.019
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发表时间：
2011-06
影响因子：
2.2
通讯作者：
Velisek, Libor
中科院分区：
文献类型：
--
作者：
Velisek, Libor
在人类中，通常在产前给予皮质类固醇以改善早产新生儿的肺发育。对接触过的儿童以及母亲在怀孕期间经历过重大压力的儿童的研究表明，行为问题和癫痫痉挛的发生率可能增加。本研究调查了产前皮质类固醇暴露是否会改变出生后早期癫痫发作的易感性和行为。在妊娠第15天，妊娠大鼠腹腔注射氢化可的松（2× 10 mg/kg）、倍他米松（2× 0.4 mg/kg）或溶剂。在生后第15天（P），用氟乙酸或红藻氨酸（3.5或5.0mg/kg）诱发癫痫发作。在癫痫发作前和P17再次测定单杠保持。在P20-22评估高架十字迷宫中的表现。出生前暴露于倍他米松可降低出生后对氟乙烯诱导的阵挛性癫痫发作的易感性，但对红藻氨酸诱导的癫痫发作无影响。产前氢化可的松降低出生后体重，但不影响癫痫发作的易感性。单独使用氢化可的松并不影响行为测试中的表现，除了在P17上改善单杠保持。产前氢化可的松和产后癫痫发作的结合导致焦虑增加。产前暴露于盐皮质激素受体阻滞剂坎利酸没有减弱，但令人惊讶的放大氢化可的松对体重的影响，并显着恶化单杠性能。因此，产前暴露于过量的皮质类固醇改变出生后癫痫发作的易感性和行为。具体作用可能取决于皮质类固醇种类。
In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hydrocortisone (2× 10 mg/kg), betamethasone (2× 0.4 mg/kg) or vehicle. On postnatal day (P)15, seizures were induced by flurothyl or kainic acid (3.5 or 5.0 mg/kg). Horizontal bar holding was determined prior to seizures and again on P17. Performance in the elevated plus maze was assessed on P20-22. Prenatal exposure to betamethasone decreased postnatal susceptibility to flurothyl-induced clonic seizures but not to kainic acid-induced seizures. Prenatal hydrocortisone decreased postnatal weight but did not affect seizure susceptibility. Hydrocortisone alone did not affect performance in behavioral tests except for improving horizontal bar holding on P17. A combination of prenatal hydrocortisone and postnatal seizures resulted in increased anxiety. Prenatal exposure to mineralocorticoid receptor blocker canrenoic acid did not attenuate, but surprisingly amplified the effects of hydrocortisone on body weight and significantly worsened horizontal bar performance. Thus, prenatal exposure to excess corticosteroids alters postnatal seizure susceptibility and behaviors. Specific effects may depend on corticosteroid species.
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