Spinal cord injury in hypertonic newborns after antenatal hypoxia-ischemia in a rabbit model of cerebral palsy.

While antenatal hypoxia-ischemia (H-I) is a well-established cause of brain injury, the effects of H-I on the spinal cord remain undefined. This study examined whether hypertonia in rabbits was accompanied by changes in spinal architecture. Rabbit dams underwent global fetal H-I at embryonic day 25 for 40min. High resolution diffusion tensor imaging was performed on fixed neonatal CNS. Fractional anisotropy (FA) and regional volumetric measurements were compared between kits with and without hypertonia after H-I and sham controls using Tract Based Spatial Statistics. Hypertonic kits showed evidence of damage from hypoxia not only in the brain, but in spinal cord as well. Hypertonic kits showed reduced FA and thickness in corticospinal tracts, external capsule, fimbria, and in white and gray matter of both cervical and lumbar spinal cord. Dorsal white matter of the spinal cord was the exception, where there was thickening and increased FA in hypertonic kits. Direct damage to the spinal cord was demonstrated in a subset of dams imaged during H-I with a 3T magnetic resonance scanner, where apparent diffusion coefficient in fetal spinal cords acutely decreased during hypoxia. Hypertonic kits showed subsequent decreases in lumbar motoneuron counts and extensive TUNEL- and Fluoro-Jade C-positive labeling was present in the spinal cord 48h after H-I, demonstrating spinal neurodegeneration. We speculate that global H-I causes significant loss of both spinal white and gray matter in hypertonic newborns due to direct H-I injury to the spinal cord as well as due to upstream brain injury and consequent loss of descending projections.