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

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.

Pubmed ID: 23325800


  • 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


Science translational medicine

Publication Data

January 16, 2013

Associated Grants

  • Agency: NINDS NIH HHS, Id: 1F30NS066704
  • Agency: NINDS NIH HHS, Id: 1R01NS054044
  • Agency: NINDS NIH HHS, Id: F30 NS066704
  • Agency: NINDS NIH HHS, Id: P30 NS061800
  • Agency: NCRR NIH HHS, Id: P51 RR000163
  • Agency: NCRR NIH HHS, Id: P51RR000163
  • Agency: NINDS NIH HHS, Id: R01 NS054044
  • Agency: NINDS NIH HHS, Id: R01 NS070022
  • Agency: NINDS NIH HHS, Id: R01NS070022
  • Agency: NINDS NIH HHS, Id: R37 NS045737
  • Agency: NINDS NIH HHS, Id: R37NS045737-06S1/06S2
  • Agency: NIA NIH HHS, Id: T32 AG023477

Mesh Terms

  • Animals
  • Anisotropy
  • Brain Ischemia
  • Cerebral Cortex
  • Dendrites
  • Dendritic Spines
  • Diffusion Magnetic Resonance Imaging
  • Disease Models, Animal
  • Premature Birth
  • Pyramidal Cells
  • Sheep