IN VIVO DETECTION OF DOPAMINERGIC DYSFUNCTION IN A RAT MODEL OF MODERATE INTRAUTERINE ASPHYXIA

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of perinatal brain injuries worldwide. Approximately one-half of all perinatal hypoxic-ischemic brain injuries are classified as `severe', leading to death, cerebral palsy, or major sensory/motor deficits by one year of age. The remaining cases are clinically defined as either `mild' or 'moderate' and have a more uncertain outcome. Though mild to moderate HIE is typically survivable, recent epidemiological evidence shows higher rates of cognitive/behavioral problems, and higher incidences of neurodevelopmental disorders including autism, ADHD, and schizophrenia. The ability of moderate, highly-survivable bouts of perinatal asphyxia to induce lifelong changes in brain development and behavior has also been demonstrated in animal models. However in human cases of moderate birth asphyxia, characterized by varying degrees of insult, and where negative outcomes may take decades to manifest themselves, developmental outcomes are unpredictable. To address this gap, the aim of this dissertation project is two-fold: (1) To establish a model of moderate intrauterine asphyxia in the full term rat that closely matches the clinical presentation of mild to moderate HIE, and (2) To identify a putative neonatal biomarker of asphyxia-mediated changes in the midbrain dopamine system and corresponding neurodevelopmental dysfunction using the cutting-edge non-invasive imaging technique proton (1H) Magnetic Resonance Spectroscopy.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2014

Author dc:creator

• Morgan, Jonathan James

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/39328

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/39328