Acute brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide.
Bilirubin toxicity produces significant neurologic and audiologic sequelae. Successful therapeutic intervention requires an understanding of the timing of neural dysfunction after exposure to bilirubin. BAEP were used in an animal model of bilirubin encephalopathy to study the onset of neural dysfunction after acute injection of a sulfonamide used to displace bilirubin out of the bloodstream and into tissue. Fourteen pairs of jaundiced Gunn rats from eight litters were studied at postnatal day 18. Baseline BAEP recordings were performed in anesthetized animals; then either sulfadimethoxine or an equal volume of saline was injected into the peritoneum. Another BAEP was done immediately, and then 2, 4, and 8 h after injection. Human serum albumin was injected into an additional 10 animals after the 2-h BAEP recording to see if induced BAEP abnormalities could be corrected. The sulfonamide-treated jj rats developed increased latencies for waves II and III, and I-II and I-III interwave intervals (p less than 0.0001). The latencies were prolonged by 2 h after injection and became progressively longer at 4 and 8 h. The amplitudes of waves II and III progressively decreased at 2, 4, and 8 h (p less than 0.0001). Latency and amplitude of waves I and IV did not change. The rats injected with albumin at 2 h showed improvement of BAEP abnormalities at 8 h. These studies show that neurophysiologic abnormalities occur as early as 2 h after intraperitoneal injection of sulfadimethoxine, and are reversible with appropriate therapy. These abnormalities are hypothesized to be due to the sulfonamide driven net transfer of free, toxic bilirubin into the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
Shapiro
S M
SM
Department of Neurology, Waisman Center, Madison, WI 53705-2280.
D000818:Animals; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D006801:Humans; D007565:Jaundice / Q000097:blood / Q000503:physiopathology*; D051381:Rats; D011911:Rats, Gunn; D011930:Reaction Time; D012709:Serum Albumin / Q000008:administration & dosage; D013412:Sulfadimethoxine / Q000633:toxicity*
D012709:Serum Albumin; D013412:Sulfadimethoxine