TY - JOUR
T1 - Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization
AU - Dean, Justin M.
AU - McClendon, Evelyn
AU - Hansen, Kelly
AU - Azimi-Zonooz, Aryan
AU - Chen, Kevin
AU - Riddle, Art
AU - Gong, Xi
AU - Sharifnia, Elica
AU - Hagen, Matthew
AU - Ahmad, Tahir
AU - Leigland, Lindsey A.
AU - Hohimer, A. Roger
AU - Kroenke, Christopher D.
AU - Back, Stephen A.
PY - 2013/1/16
Y1 - 2013/1/16
N2 - 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.
AB - 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.
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U2 - 10.1126/scitranslmed.3004669
DO - 10.1126/scitranslmed.3004669
M3 - Article
C2 - 23325800
AN - SCOPUS:84872582526
SN - 1946-6234
VL - 5
SP - 168ra7
JO - Science translational medicine
JF - Science translational medicine
IS - 168
ER -