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.
Shapiro, S M (1991) Binaural effects in brainstem auditory evoked potentials of jaundiced Gunn rats. Hear Res 53:41-8 |
Conlee, J W; Shapiro, S M (1991) Morphological changes in the cochlear nucleus and nucleus of the trapezoid body in Gunn rat pups. Hear Res 57:23-30 |
Shapiro, S M; Conlee, J W (1991) Brainstem auditory evoked potentials correlate with morphological changes in Gunn rat pups. Hear Res 57:16-22 |
Shapiro, S M; Hecox, K E (1989) Brain stem auditory evoked potentials in jaundiced Gunn rats. Ann Otol Rhinol Laryngol 98:308-17 |
Shapiro, S M; Hecox, K E (1988) Development of brainstem auditory evoked potentials in heterozygous and homozygous jaundiced Gunn rats. Brain Res 469:147-57 |
Shapiro, S M (1988) Acute brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide. Pediatr Res 23:306-10 |