Unmyelinated axon loss with postnatal hypertonia after fetal hypoxia
Article first published online: 13 MAR 2014
© 2014 American Neurological Association
Annals of Neurology
Volume 75, Issue 4, pages 533–541, April 2014
How to Cite
Drobyshevsky, A., Jiang, R., Lin, L., Derrick, M., Luo, K., Back, S. A. and Tan, S. (2014), Unmyelinated axon loss with postnatal hypertonia after fetal hypoxia. Ann Neurol., 75: 533–541. doi: 10.1002/ana.24115
- Issue published online: 5 MAY 2014
- Article first published online: 13 MAR 2014
- Accepted manuscript online: 6 FEB 2014 04:59AM EST
- Manuscript Accepted: 3 FEB 2014
- Manuscript Revised: 31 JAN 2014
- Manuscript Received: 3 AUG 2013
White matter (WM) injury due to myelination defects is believed to be responsible for the motor deficits seen in cerebral palsy. We tested the hypothesis that the predominant injury is to functional electrical connectivity in unmyelinated WM fibers by conducting a longitudinal study of central WM tracts in newborn rabbit kits with hypertonia in our model of cerebral palsy.
Pregnant rabbits at 70% gestation underwent 40-minute uterine ischemia. Motor deficits in newborn kits, including muscle hypertonia, were assessed by neurobehavioral testing. Major central WM tracts, including internal capsule, corpus callosum, anterior commissure, and fimbria hippocampi, were investigated for structural and functional injury using diffusion tensor magnetic resonance imaging (MRI), electrophysiological recordings of fiber conductivity in perfused brain slices, electron microscopy, and immunohistochemistry of oligodendrocyte lineage.
Motor deficits were observed on postnatal day 1 (P1) when WM tracts were unmyelinated. Myelination occurred later and was obvious by P18. Hypertonia was associated with microstructural WM injury and unmyelinated axon loss at P1, diagnosed by diffusion tensor MRI and electron microscopy. Axonal conductivity from electrophysiological recordings in hypertonic P18 kits decreased only in unmyelinated fibers, despite a loss in both myelinated and unmyelinated axons.
Motor deficits in cerebral palsy were associated with loss of unmyelinated WM tracts. The contribution of injury to myelinated fibers that was observed at P18 is probably a secondary etiological factor in the motor and sensory deficits in the rabbit model of cerebral palsy. Ann Neurol 2014;75:533–541