Validation of the ovine fetus as an experimental model for the human myelomeningocele defect: a pilot study

Abstract

Objective: To produce a myelomeningocele-like human defect inthe ovine fetus and validate this experimental model in ourpopulation. Methods: A prospective study on 12 pregnant sheep ofa crossed Hampshire/Down breed where a spinal defect wassurgically created between day 75 and day 77 after conception.The technique consisted of a hysterotomy with exposure of fetalhind limbs and tail up to the mid spine. Fetal skin, paravertebralmuscles, and 4 posterior spinal arches were excised, exposingthe spinal cord. Duramater was opened and the medulla was inciseduntil the medullar canal. Animals were euthanized at 139 days ofgestation for fetal evaluation. The central nervous system wassubmitted to post-mortem magnetic resonance imaging (MRI) andthe spine was submitted to pathological examination. Results:The defect was created in 13 fetuses and 5 survived. Meangestational age at necropsy was 121.6 days (varying from 93 to145 days). Macroscopically, the defect was present in 4 cases.Microscopy revealed a flattened medulla with disappearance ofthe medullar canal and disruption of normal medullar cellarchitecture with neuronal apoptosis and/or fusion of the piamaterand duramater. The MRI showed herniation of the cerebellum intothe cervical canal and syringomyelia. Conclusions: The surgicallyproduced defect mimics defects in the human fetus, including theArnold-Chiari malformation. Post-mortem MRI was used for thefirst time in our study and proved an excellent alternative fordemonstrating the cerebellar herniation. We standardized thetechnique for creating the defect in our population.

Keywords

• Animals
• model
• Meningomyelocele/surgery
• Spinal dysraphism
• Sheep
• Fetus/surgery