Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Neurosciences

Language

English (en)

Date of Award

5-24-2012

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Jeffrey Neil

Abstract

Nearly 13% of infants born in the United States each year are preterm - that is, born before 37 weeks gestation. Although improvements in clinical care have contributed to survival rates that now exceed 85%, premature infants are at high risk for motor, sensory, cognitive and behavioral disabilities. In order to develop therapeutic interventions to prevent these adverse neurodevelopmental outcomes, we must first understand the nature of cerebral injury associated with premature birth and the mechanisms by which it leads to altered brain development. A baboon: Papio papio) model of preterm birth was used to evaluate cerebral development from 90 days of gestation: dg) to term: ∼ 185 dg). Conventional magnetic resonance imaging: MRI) and diffusion tensor imaging: DTI) was obtained on fixed brains. In addition, histopathology was obtained. Analysis of this model led to the following conclusions.: 1) MRI/DTI findings during brain maturation closely paralleled those from live premature infants, indicating that the preterm baboon is a good model of human development.: 2) Both qualitative MRI scoring and quantitative analysis of DTI parameters correlated with pathologic abnormalities in cerebral white matter. In particular, reduced oligodendrocyte number was associated with increased radial diffusivity and decreased diffusion anisotropy, while astrocytosis corresponded to increased apparent diffusion coefficient.: 3) The birth weight of control animals correlated strongly with cerebral development as measured with MRI/DTI, with lower weight corresponding to less mature brain. Since birth weight may be an indicator of the quality of the intrauterine environment, it may better predict cerebral growth and maturation than gestational age.: 4) Clinical therapies differentially affect cerebral development and provide opportunities for neuroprotection. Positive pressure and high frequency ventilation were associated with more cerebral injury: as measured using both histology and MRI/DTI) than nasal continuous positive airway pressure.: 5) High-dose erythropoietin, a novel neuroprotective agent, had no adverse effects on cerebral development and may increase the potential for cerebral repair by inducing proliferation of cells in the subventricular zone.

Comments

Permanent URL: http://dx.doi.org/10.7936/K7K35RPH

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