This project begins a long term study which will investigate perinatal brain damage in an animal model, using the technique of brainstem auditory evoked potentials (BAEPs) as an indicator of neurological dysfunction. The Gunn rat model is chosen because the biochemistry and pathology have already been intensively studied, and because neurological disabilities and hearing loss secondary to bilirubin encephalopathy are significant problems in humans. BEEPs will be studied in hyperbilirubinemic homozygous (glucuronyl transferase deficient) Gunn rats made encephalopathic with sulfadimethoxine (which releases free bilirubin from plasma albumin). Heterozygote and non-treated homozygote littermates will serve as controls. The relationship of auditory nervous system dysfunction to the amount and duration of bilirubin toxicity will be studied at different stages in developement. Proper controls for these studies include the definition of the time course and nature of electrophysiologic maturation in normals. BAEP changes in the affected animals will be correlated with total and free serum bilirubin, regional brain bilirubin concentration, brain and inner ear histology, behavioral responses and finally, intracranial single unit physiological recordings. The overall goal is to improve our understanding of the mechanisms by which elevated bilirubin produces neurologic and auditory dysfunction, provide detailed information on the nature of auditory development in the rat, anatomically localize the pathology of bilirubin induced hearing loss, and develop an animal model which will be useful in the investigation of many factors known to cause of modulate brain damage in the perinatal period.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000829-04
Application #
3078195
Study Section
Communicative Disorders Review Committee (CDR)
Project Start
1984-01-01
Project End
1988-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715