Abstract

Bilirubin encephalopathy, the result of bilirubin toxicity to the brain, causes brain damage and deafness. The pathogenesis and site(s) of auditory nervous system dysfunction in bilirubin encephalopathy are still unknown and controversial despite decades of study. Brainstem auditory evoked potentials (BAEPs), histology, and biochemical assays will be applied to the Gunn rat model of bilirubin encephalopathy to define the site(s) of auditory dysfunction, its time course, interaction with development, and potential for reversibility. The project will use BAEPs to assess neurophysiological changes occurring soon after acute exposure to bilirubin toxicity. BAEP findings will be compared to measurements of free and protein- bound blood bilirubin, and then to histological findings. Studies at different ages will examine the increased vulnerability of the immature central nervous system to bilirubin toxicity. Interventions aimed at decreasing bilirubin toxicity will explore the time constraints of reversibility of the pathological process. In related studies, the project will localize the specific site(s) of bilirubin induced auditory nervous system dysfunction. BAEPs and histology will be compared to verify the status of the cochlea and the auditory brainstem nuclei. The findings will also be related to the previously described biochemical studies. The resulting multidisciplinary approach is expected to provide new insights into the pathogenesis of this disorder and its effects on the auditory system. And understanding of the complex relationships between electrophysiological, anatomical and biochemical processes should lead to improved noninvasive procedures (e.g. BAEPs and blood tests) for predicting neurological and otological sequelae in human newborns.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS023895-02
Application #
3564492
Study Section
Hearing Research Study Section (HAR)
Project Start
1988-09-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Virginia Commonwealth University
Department
Type
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298