Ikonomidou C, Bittigau P, Koch C, Genz K, Hoerster F, Felderhoff-Mueser U, Tenkova T, Dikranian K, Olney J W
Department of Pediatric Neurology, Charité, Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany.
Biochem Pharmacol. 2001 Aug 15;62(4):401-5. doi: 10.1016/s0006-2952(01)00696-7.
In the immature mammalian brain during a period of rapid growth (brain growth spurt/synaptogenesis period), neuronal apoptosis can be triggered by the transient blockade of glutamate N-methyl-d-aspartate (NMDA) receptors, or the excessive activation of gamma-aminobutyric acid (GABA(A)) receptors. Apoptogenic agents include anesthetics (ketamine, nitrous oxide, isoflurane, propofol, halothane), anticonvulsants (benzodiazepines, barbiturates), and drugs of abuse (phencyclidine, ketamine, ethanol). In humans, the brain growth spurt period starts in the sixth month of pregnancy and extends to the third year after birth. Ethanol, which has both NMDA antagonist and GABA(A) agonist properties, is particularly effective in triggering widespread apoptotic neurodegeneration during this vulnerable period. Thus, maternal ingestion of ethanol during the third trimester of pregnancy can readily explain the dysmorphogenic changes in the fetal brain and consequent neurobehavioral disturbances that characterize the human fetal alcohol syndrome. In addition, there is basis for concern that agents used in pediatric and obstetrical medicine for purposes of sedation, anesthesia, and seizure management may cause apoptotic neuronal death in the developing human brain.
在未成熟哺乳动物大脑快速生长时期（脑发育激增/突触发生期），谷氨酸N-甲基-D-天冬氨酸（NMDA）受体的短暂阻断或γ-氨基丁酸（GABA(A)）受体的过度激活可引发神经元凋亡。凋亡诱导剂包括麻醉剂（氯胺酮、氧化亚氮、异氟烷、丙泊酚、氟烷）、抗惊厥药（苯二氮卓类、巴比妥类）和滥用药物（苯环利定、氯胺酮、乙醇）。在人类，脑发育激增期始于妊娠第六个月，并持续到出生后第三年。具有NMDA拮抗剂和GABA(A)激动剂特性的乙醇，在这个脆弱时期特别有效地引发广泛的凋亡性神经退行性变。因此，孕期第三个月母体摄入乙醇很容易解释胎儿大脑的畸形变化以及随之而来的以人类胎儿酒精综合征为特征的神经行为障碍。此外，人们有理由担心，儿科和产科医学中用于镇静、麻醉和癫痫管理的药物可能会导致发育中的人类大脑发生凋亡性神经元死亡。
