Central nervous system malformations induced by triamcinolone acetonide in nonhuman primates: pathology.
Central nervous system malformations induced by triamcinolone acetonide in nonhuman primates: pathology.
复制标题
非人灵长类动物中曲安奈德诱发的中枢神经系统畸形：病理学。
DOI：
10.1002/tera.1420390109
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Hendrickx,AG
中科院分区：
文献类型：
--
作者：
Tarara,RP;Cordy,DR;Hendrickx,AG
用曲安奈德(TAC)对怀孕猕猴(Macaca mulatta[15]和M.Radiata[7])在妊娠23至41天(GD)期间使用不同的剂量计划。每天10毫克/公斤的剂量相当于人体剂量当量的100倍≅。对胎儿和婴儿的大脑进行了大体和组织学研究。所有病例均表现为轻度的TAC诱导综合征(颅面畸形、隐匿性颅裂、脑膜膨出和轻度中脑变形)或较严重的形式(枕部脑膨出、脑积水、中脑或中脑严重变形或“喙”、脑脊液分流和颅面畸形)。畸形与剂量有关，随着剂量的增加或治疗次数的增加，严重程度增加。通过比较组间相似成分来评估个别病例的症状严重程度。观察到的病变在形态上与自发性人类病例中描述的病变相似；TAC诱导的枕叶脑膨出与脑干和小脑异常有关，随着症状的减轻，偶尔也会出现脑干异常，伴有枕部脑膜膨出。关于中脑变化的意义和时间发展存在争议。然而，导水管构型的相关改变可能是导致功能损害和随后的脑积水的原因。
Triamcinolone acetonide (TAC) was administered to pregnant macaques (Macaca mulatta[15] andM. radiata[7]) during gestational days (GD) 23 to 41 using various dosing schedules. A daily dose of 10 mg/kg is ≅ 100 × 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.