Reversible brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide.
Neurologic and audiologic sequelae produced by bilirubin toxicity are preventable by appropriately timed therapeutic intervention. To understand the timing and reversibility of the neural dysfunction that follows exposure to bilirubin, we recorded brainstem auditory evoked potentials (BAEP) in the Gunn rat model of bilirubin encephalopathy. Abnormal BAEP occur in jaundiced Gunn rats after injection of sulfadimethoxine (sulfa) 100 mg/kg intraperitoneally, which displaces bilirubin from blood albumin binding sites and promotes the net transfer of bilirubin into brain tissue. Reversal of BAEP abnormalities with injection of human serum albumin (HSA) 2 g/kg intraperitoneally was studied in 17- to 20-d-old jaundiced Gunn rats. One animal from each of 14 litters was randomly assigned to one of the following treatment groups: 1) sulfa alone, 2) sulfa + HSA at 2 h, 3) sulfa + HSA at 8 h, or 4) saline alone. BAEP were recorded in each rat before and 0.1, 4, 8, 24, and 48 h after injection of sulfa or saline. BAEP I-II interwave intervals increased in all sulfa groups (p < 10(-9) to 0.27 ms (21%) above baseline at 8 h for the two sulfa groups not receiving treatment before that time (p = 0.0002), but increased less for the sulfa group given HSA at 2 h compared with untreated animals (p = 0.02). Partial recovery of function occurred at 24 and 48 h for both HSA-treated groups compared with their 8-h values (p = 0.001), and there was increased mortality at 24 h for the sulfa group not treated with HSA (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Shapiro
S M
SM
Department of Neurology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0211.
D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007565:Jaundice / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D011911:Rats, Gunn; D012709:Serum Albumin / Q000627:therapeutic use*; D013412:Sulfadimethoxine / Q000633:toxicity*
D012709:Serum Albumin; D013412:Sulfadimethoxine; D001663:Bilirubin