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

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 synaptic 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.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

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 CD,Back SA

doi

10.1126/scitranslmed.3004669

subject

Has Abstract

pub_date

2013-01-16 00:00:00

pages

168ra7

issue

168

eissn

1946-6234

issn

1946-6242

journal_volume

5

pub_type

杂志文章

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