Department of Neurology, Dartmouth-Hitchcock Medical Center, Neuroscience Center at Dartmouth, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA.
Clin Perinatol. 2009 Dec;36(4):901-14, vii-viii. doi: 10.1016/j.clp.2009.07.012.
The highest incidence of seizures occurs during the first hours to days after birth. The immature brain is prone to seizures because of reduced inhibition. GABA, which is the primary inhibitory neurotransmitter in the mature brain, is depolarizing and excitatory in the immature brain. Seizures are an ominous sign, indicating either an acquired brain insult or a genetic abnormality. While the primary outcome determinant of neonatal seizures is etiology, whether seizures can result in long-term adverse consequences independently is not clear. While the clinical data is uncertain, there is now a considerable body of evidence indicating that in animals, neonatal seizures can adversely alter the developing brain. Animal data indicates that the sequelae of seizures are strongly age dependent; seizures will affect the developing and plastic neuronal circuitry much differently than the fixed circuitry of the mature brain. Seizures at an early developmental stage can dramatically affect the construction of networks, resulting in severe and permanent handicaps in some patients. In the young brain, the long-lasting detrimental consequences of seizures are caused by an alteration of developmental programs rather than by neuronal cell loss, as occurs in adults. In animal models, neonatal seizures result in decreases in neurogenesis, sprouting of mossy fibers, and long-standing changes in signaling properties. Seizures in rat pups are also associated with abnormalities in firing patterns of single cells in the hippocampus. Furthermore, these anatomic and physiologic changes correlate well with behavioral dysfunction.
癫痫发作的最高发生率发生在出生后的头几个小时到几天内。由于抑制作用减弱，不成熟的大脑容易发生癫痫发作。GABA 是成熟大脑中的主要抑制性神经递质，但在不成熟的大脑中却是去极化和兴奋的。癫痫发作是一个严重的迹象，表明存在后天性脑损伤或遗传异常。虽然新生儿癫痫的主要结局决定因素是病因，但癫痫是否能独立导致长期不良后果尚不清楚。虽然临床数据不确定，但现在有相当多的证据表明，在动物中，新生儿癫痫会对发育中的大脑产生不利影响。动物数据表明，癫痫发作的后遗症强烈依赖于年龄；与成熟大脑的固定电路相比，癫痫发作将对发育中的、具有可塑性的神经元电路产生大不相同的影响。早期发育阶段的癫痫发作会极大地影响网络的构建，导致一些患者出现严重和永久性残疾。在年轻的大脑中，癫痫发作引起的长期不良后果是由于发育程序的改变，而不是像在成人中那样由神经元细胞丢失引起的。在动物模型中，新生儿癫痫会导致神经发生减少、苔藓纤维发芽以及信号转导特性的长期改变。大鼠幼仔的癫痫发作还与海马单个细胞放电模式的异常有关。此外，这些解剖和生理变化与行为功能障碍密切相关。
