Prenatal Cerebral Ischemia Disrupts MRI-Defined Cortical Microstructure Through Disturbances in Neuronal Arborization

Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
Science translational medicine (Impact Factor: 15.84). 01/2013; 5(168):168ra7. DOI: 10.1126/scitranslmed.3004669
Source: PubMed


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.

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    • "Furthermore , structural development of the cortex can be detected with the DT model (Neil et al., 1998; McKinstry et al., 2002b), but the model's specificity is limited, because multiple features of the microstructure have similar effects on tensor characteristics (Vos et al., 2011, 2012). For example, the decrease in anisotropy observed over cortical development is thought to results from emerging dendritic arborization (Dean et al., 2013), but the same anisotropy decrease could also result from, for instance a reduction in radial glial fibers (Sizonenko et al., 2007). Most likely, these different changes happen concurrently and therefore it is essential to distinguish these contributions and other microstructural features, not only with postmortem techniques, but also with in vivo methods such as diffusion MRI. "
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