Hypoxic-ischemic (HI) encephalopathy is a common problem impacting thousands of Americans. Animal models have been created to allow for a greater understanding of the process and determine the efficacy of pharmaceutical agents. One of these is the hypoxia-ischemia model of Levine. We propose to use this model to test the hypothesis that the outcome of neuroprotection is not always positive;that certain neurological outcomes may not improve in spite of a reduction in histological damage. It is possible that saving injured tissue facilitates formation of aberrant neuronal circuits resulting in adverse outcomes.
The Specific Aims of the project are to develop seizure detection algorithms and to determine the impact of neuroprotection on chronic seizure frequency and histological damage. This proposal describes a 5 year training program to investigate the impact of neuroprotection in neonatal HI encephalopathy. The principal investigator has completed his Pediatric Neurology residency at the Univ. of Co. at Denver and Health Sciences Center (UCDHSC). He has a PhD in Nuclear Engineering and has worked at two national laboratories prior to entering medicine. He began his research in the field of pediatric epilepsy with a grant from the Epilepsy Foundation, and will now prepare for a career in academics by obtaining further training in the basic sciences. Mentors for laboratory research training are: 1) Kevin Staley, Chief of Neurology at The Children's Hospital - Denver, an expert in the field of cellular mechanisms of epilepsy, and, 2) Edward Dudek, Ph.D., Professor, Department of Physiology, University of Utah, a leader in the field of animal models of epilepsy and epileptogenesis. Along with the laboratory work, the principle investigator will enroll in a certificate program which includes graduate level course work in the areas of numerical analysis, biostatistics, ethics and research methods. In addition to the research described above, he will also conduct clinics in pediatric neurology, and will have in-patient consultant responsibilities (15% of his time). An advisory committee of physicians and scientists from the Neuroscience Program at UCDHSC will provide guidance and direction to the principle investigator. The goal of this proposal is to furnish the additional laboratory and analytical skills and technical background necessary to launch a career in neurosciences while furthering research in the area of spike/seizure detection and neuroprotection.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Clinical Investigator Award (CIA) (K08)
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Study Section
NST-2 Subcommittee (NST)
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Koenig, James I
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University of Colorado Denver
Schools of Medicine
United States
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Sampath, Dayalan; White, Andrew M; Raol, Yogendra H (2014) Characterization of neonatal seizures in an animal model of hypoxic-ischemic encephalopathy. Epilepsia 55:985-93
Staley, Kevin J; White, Andrew; Dudek, F Edward (2011) Interictal spikes: harbingers or causes of epilepsy? Neurosci Lett 497:247-50
Kadam, Shilpa D; White, Andrew M; Staley, Kevin J et al. (2010) Continuous electroencephalographic monitoring with radio-telemetry in a rat model of perinatal hypoxia-ischemia reveals progressive post-stroke epilepsy. J Neurosci 30:404-15
White, Andrew; Williams, Philip A; Hellier, Jennifer L et al. (2010) EEG spike activity precedes epilepsy after kainate-induced status epilepticus. Epilepsia 51:371-83