Therapeutic strategies to avoid long-term adverse outcomes of neonatal antiepileptic drug exposure.
Therapeutic strategies to avoid long-term adverse outcomes of neonatal antiepileptic drug exposure.
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DOI：
10.1111/j.1528-1167.2010.02603.x
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发表时间：
2010-07
期刊：
影响因子：
5.6
通讯作者：
Gale K
中科院分区：
文献类型：
--
作者：
Forcelli PA;Janssen MJ;Stamps LA;Sweeney C;Vicini S;Gale K
苯巴比妥、苯妥英和丙戊酸等抗癫痫药物（AED）以治疗剂量给予新生大鼠时，会导致明显的神经元凋亡细胞死亡。这种效应在产后第二周的纹状体和皮质中尤其明显。相当于人类“大脑生长突增”（妊娠晚期和婴儿早期）的时期。特别令人担忧的是，苯巴比妥是新生儿癫痫最常用的治疗方法。如果 AED 诱导的神经细胞死亡导致长期功能损伤，那么找到在敏感期避免这种神经毒性的治疗方法就变得至关重要。在这里，我们检查了新生大鼠幼崽暴露于苯巴比妥后的短期和长期功能影响；测试的功能包括幼犬的纹状体 GABA 突触反应和反射发育，以及成年犬的恐惧调节、情绪和感觉运动门控。在所有情况下，出生后第二周接触苯巴比妥足以造成明显的损害。相比之下，成年动物在幼崽时暴露于拉莫三嗪（给予的剂量不会导致神经元凋亡）在我们检查的任务中并没有受到损害。我们的数据表明，缺乏促凋亡作用的治疗可能是避免新生儿暴露后不良后果的有前途的疗法。此外，我们的研究结果表明，早期接触某些 AED 是导致晚年精神和神经系统异常的重要潜在危险因素。
Antiepileptic drugs (AEDs) such as phenobarbital, phenytoin and valproic acid, when given in therapeutic doses to neonatal rats, cause pronounced neuronal apoptotic cell death. This effect is especially pronounced in the striatum and cortex during the second postnatal week; a period corresponding to the “brain growth spurt” (third trimester of gestation and early infancy) in humans. Of particular concern is the fact that phenobarbital is the most frequently used therapy for neonatal epilepsy. If AED-induced neuronal cell death leads to long-term functional impairment, then it becomes crucial to find therapies that avoid this neurotoxicity in the sensitive period. Here we examine short and long-term functional effects following exposure of neonatal rat pups to phenobarbital; the functions tested include striatal GABAergic synaptic responses and reflex development in pups, and fear conditioning, emotionality, and sensory-motor gating in adults. In all cases, phenobarbital exposure during the second postnatal week was sufficient to cause significant impairment. In contrast, adult animals exposed as pups to lamotrigine (given in a dose that does not cause apoptotic neuronal death) were not impaired on the tasks we examined. Our data suggest that treatments devoid of proapoptotic actions may be promising therapies for avoiding adverse outcomes after neonatal exposure. In addition, our findings identify early exposure to certain AEDs as an important potential risk factor contributing to psychiatric and neurological abnormalities later in life.
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影响因子：
5.1
作者：
Glass, Hannah C.;Glidden, David;Jeremy, Rita J.;Barkovich, A. James;Ferriero, Donna M.;Miller, Steven P.
通讯作者：
Miller, Steven P.
DOI：
10.1016/0736-5748(85)90027-9
发表时间：
1985-01-01
影响因子：
1.8
作者：
PICK, CG;YANAI, J
通讯作者：
YANAI, J
影响因子：
3.9
作者：
Wagner, George C.;Reuhl, Kenneth R.;Halladay, Alycia K.
通讯作者：
Halladay, Alycia K.
影响因子：
8
作者：
Tekgul, H;Gauvreau, K;du Plessis, AJ
通讯作者：
du Plessis, AJ
影响因子：
5.6
作者：
HAUSER, WA;ANNEGERS, JF;KURLAND, LT
通讯作者：
KURLAND, LT