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, Alan (Roger) Hohimer, Christopher (Chris) Kroenke, Stephen Back

Research output: Contribution to journalArticle

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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)
JournalScience Translational Medicine
Volume5
Issue number168
DOIs
StatePublished - Jan 16 2013

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Neuronal Plasticity
Anisotropy
Brain Ischemia
Learning Disorders
Premature Birth
Growth
Diffusion Magnetic Resonance Imaging
Pyramidal Cells
Nervous System Diseases
Synapses
Ischemia
Animal Models
Neurons

ASJC Scopus subject areas

  • Medicine(all)

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Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization. / Dean, Justin M.; McClendon, Evelyn; Hansen, Kelly; Azimi-Zonooz, Aryan; Chen, Kevin; Riddle, Art; Gong, Xi; Sharifnia, Elica; Hagen, Matthew; Ahmad, Tahir; Leigland, Lindsey A.; Hohimer, Alan (Roger); Kroenke, Christopher (Chris); Back, Stephen.

In: Science Translational Medicine, Vol. 5, No. 168, 16.01.2013.

Research output: Contribution to journalArticle

Dean, JM, McClendon, E, Hansen, K, Azimi-Zonooz, A, Chen, K, Riddle, A, Gong, X, Sharifnia, E, Hagen, M, Ahmad, T, Leigland, LA, Hohimer, AR, Kroenke, CC & Back, S 2013, 'Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization', Science Translational Medicine, vol. 5, no. 168. https://doi.org/10.1126/scitranslmed.3004669
Dean, Justin M. ; McClendon, Evelyn ; Hansen, Kelly ; Azimi-Zonooz, Aryan ; Chen, Kevin ; Riddle, Art ; Gong, Xi ; Sharifnia, Elica ; Hagen, Matthew ; Ahmad, Tahir ; Leigland, Lindsey A. ; Hohimer, Alan (Roger) ; Kroenke, Christopher (Chris) ; Back, Stephen. / Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization. In: Science Translational Medicine. 2013 ; Vol. 5, No. 168.
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