Tarara R P, Cordy D R, Hendrickx A G
California Primate Research Center, Davis.
Teratology. 1989 Jan;39(1):75-84. doi: 10.1002/tera.1420390109.
Triamcinolone acetonide (TAC) was administered to pregnant macaques (Macaca mulatta [15] and M. radiata [7]) during gestational days (GD) 23 to 41 using various dosing schedules. A daily dose of 10 mg/kg is approximately equal to 100 x the human dose equivalent. The brains of the fetuses and infants were studied grossly and histologically. All cases displayed either the mild form of the TAC-induced syndrome (craniofacial dysmorphia, cranium bifidum occultum, meningocele, and mild distortion of the midbrain) or the more severe form (occipital encephalocele, hydrocephalus, severe distortion of the midbrain or midbrain "beaking," shunting of cerebrospinal fluid, and craniofacial malformations). The dysmorphology was dose-related, with severity increasing at higher doses or with increased numbers of treatments. Individual cases were assessed for the severity of the syndrome by comparison of like components between groups. The lesions observed were morphologically comparable to those described in spontaneous human cases; the TAC-induced occipital encephaloceles were associated with brainstem and cerebellar abnormalities, and, with the less severe form of the syndrome, brainstem abnormalities were occasionally present, with occipital meningoceles. Controversy exists concerning the significance and temporal development of the midbrain changes. However, the associated alteration in aqueduct conformation may have been responsible for functional compromise and ensuing hydrocephalus.
在妊娠第23至41天期间，使用不同的给药方案，对怀孕的猕猴（恒河猴[15只]和辐射猴[7只]）给予曲安奈德（TAC）。每日剂量10mg/kg约等于人类等效剂量的100倍。对胎儿和婴儿的大脑进行大体和组织学研究。所有病例均表现出TAC诱导综合征的轻度形式（颅面畸形、隐性颅裂、脑膜膨出和中脑轻度变形）或更严重的形式（枕部脑膨出、脑积水、中脑严重变形或中脑“喙状”、脑脊液分流和颅面畸形）。畸形与剂量相关，在较高剂量或治疗次数增加时严重程度增加。通过比较组间相似成分来评估个体病例综合征的严重程度。观察到的病变在形态上与人类自发病例中描述的病变相似；TAC诱导的枕部脑膨出与脑干和小脑异常有关，并且在综合征较轻的形式中，偶尔会出现脑干异常和枕部脑膜膨出。关于中脑变化的意义和时间发展存在争议。然而，导水管形态的相关改变可能是导致功能损害和随后脑积水的原因。
