The fetal spinal cord does not regenerate after in utero transection in a large mammalian model

OBJECTIVE: Regeneration and functional recovery after spinal cord transection do not occur in mammalian animals and humans postnatally. The goal of this study was to test whether in utero transection of the fetal spinal cord is succeeded by anatomic healing and functional recovery. METHODS: In five sheep fetuses, at 60 days of gestation and 75 days of gestation (term = 150 d), the spinal cord was completely transected at T10. The animals were delivered near term by cesarean section for clinical evaluation, measurement of cortical somatosensory evoked potentials, and morphological assessment. RESULTS: The newborn lambs demonstrated sensory- motor paraplegia, were incontinent of urine and stool, and exhibited a spinally generated, ambulatory pattern of the hindlimbs. No cortical somatosensory evoked potentials could be recorded in response to posterior tibial nerve stimulation, although potentials from the ulnar nerve, which enters the cord rostral to the lesion, were normal in all animals. Histologically, no neuronal connections across the transection site were identified. The cord proximal to the lesion was grossly normal, whereas distal to the transection, it appeared slightly smaller but with the cytoarchitecture preserved. CONCLUSIONS: Unlike in lower vertebrate and avian species, the fetal ovine spinal cord has no detectable spontaneous regenerative capabilities when transected during midgestation. Gap formation after transection, secondary posttraumatic cell death, and missing guiding channels for sprouting axons may be factors involved in the absence of any regenerative response.