Central nervous system malformations induced by triamcinolone acetonide in nonhuman primates: pathogenesis.
The pathogenetic sequence for TAC-induced encephalocele is in agreement with hypotheses proposing that neural tube closure is followed by protrusion of the mesencephalon, with subsequent growth and development resulting in herniation of the cerebrum and cerebellum. This model could serve to clarify the pathogenesis of encephalocele and to stimulate further study in comparing this defect to other dysraphic states. Triamcinolone acetonide (TAC) was administered intramuscularly (10 mg/kg) to 16 pregnant rhesus monkeys (Macaca mulatta) for 5 alternate days of pregnancy, beginning on gestational day (GD) 23. Conceptuses were removed by hysterotomy at GD 35, 42, 50, or 70 and examined grossly and histologically. Length, area, and perimeter of the tectum and aqueduct area and perimeter were measured with an image analyzer. Changes in treated specimens were suggestive of forces within or ventral to the tectum resulting in dorsal protrusion, rostral-posterior stretching, and attenuation. The angle of the cephalic, pontine, and cervical flexures was also measured. The more acute angle of the cephalic flexure and less acute cervical flexure of treated specimens could represent altered orientation secondary to a mesenchymal deficiency. However, the less acute angle of the pontine flexure in treated specimens suggests an intrinsic alteration in the neural tube. This suggests that encephalocele may result from a combination of mesenchymal and neural tube abnormalities.
Tarara
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California Primate Research Center, University of California, Davis 95616.
Wheeldon
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EB
Hendrickx
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D000818:Animals; D002490:Central Nervous System / Q000002:abnormalities* / Q000187:drug effects / Q000196:embryology; D004677:Encephalocele / Q000139:chemically induced*; D005260:Female; D005865:Gestational Age; D008253:Macaca mulatta; D011247:Pregnancy; D013723:Teratogens; D014222:Triamcinolone Acetonide / Q000633:toxicity*
D013723:Teratogens; D014222:Triamcinolone Acetonide