Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization

Justin M. Dean, Evelyn McClendon, Kelly Hansen, Aryan Azimi-Zonooz, Kevin Chen, Art Riddle, Xi Gong, Elica Sharifnia, Matthew Hagen, Tahir Ahmad, Lindsey A. Leigland, A. Roger Hohimer, Christopher D. Kroenke, Stephen A. Back

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Children who survive preterm birth exhibit persistent unexplained disturbances in cerebral cortical growth with associated cognitive and learning disabilities. The mechanisms underlying these deficits remain elusive. We used ex vivo diffusion magnetic resonance imaging to demonstrate in a preterm large-animal model that cerebral ischemia impairs cortical growth and the normal maturational decline in cortical fractional anisotropy (FA). Analysis of pyramidal neurons revealed that cortical deficits were associated with impaired expansion of the dendritic arbor and reduced syn-aptic density. Together, these findings suggest a link between abnormal cortical FA and disturbances of neuronal morphological development. To experimentally investigate this possibility, we measured the orientation distribution of dendritic branches and observed that it corresponds with the theoretically predicted pattern of increased anisotropy within cases that exhibited elevated cortical FA after ischemia. We conclude that cortical growth impairments are associated with diffuse disturbances in the dendritic arbor and synapse formation of cortical neurons, which may underlie the cognitive and learning disabilities in survivors of preterm birth. Further, measurement of cortical FA may be useful for noninvasively detecting neurological disorders affecting cortical development.

Original languageEnglish (US)
Pages (from-to)168ra7
JournalScience translational medicine
Volume5
Issue number168
DOIs
StatePublished - Jan 16 2013

ASJC Scopus subject areas

  • Medicine(all)

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    Dean, J. M., McClendon, E., Hansen, K., Azimi-Zonooz, A., Chen, K., Riddle, A., Gong, X., Sharifnia, E., Hagen, M., Ahmad, T., Leigland, L. A., Hohimer, A. R., Kroenke, C. D., & Back, S. A. (2013). Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization. Science translational medicine, 5(168), 168ra7. https://doi.org/10.1126/scitranslmed.3004669