title: 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.
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Justin M
authors: JM
authors: Dean
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Evelyn
authors: E
authors: McClendon
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Kelly
authors: K
authors: Hansen
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Aryan
authors: A
authors: Azimi-Zonooz
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Kevin
authors: K
authors: Chen
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Art
authors: A
authors: Riddle
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Xi
authors: X
authors: Gong
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Elica
authors: E
authors: Sharifnia
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Matthew
authors: M
authors: Hagen
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Tahir
authors: T
authors: Ahmad
authors: Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR 97239, USA.|Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Lindsey A
authors: LA
authors: Leigland
authors: Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA.
authors: A Roger
authors: AR
authors: Hohimer
authors: Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR 97239, USA.|Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Christopher D
authors: CD
authors: Kroenke
authors: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.|Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Stephen A
authors: SA
authors: Back
mesh_terms: D000818:Animals; D016880:Anisotropy; D002545:Brain Ischemia / Q000473:pathology*; D002540:Cerebral Cortex / Q000254:growth & development / Q000473:pathology*; D003712:Dendrites / Q000473:pathology*; D049229:Dendritic Spines / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D047928:Premature Birth / Q000473:pathology*; D017966:Pyramidal Cells / Q000473:pathology; D012756:Sheep