NMDA channel antagonist MK-801 does not protect against bilirubin neurotoxicity.
Neonatology
; 92(4): 248-57, 2007.
Article
en En
| MEDLINE
| ID: mdl-17556843
ABSTRACT
BACKGROUND:
Bilirubin encephalopathy or kernicterus is a potentially serious complication of neonatal hyperbilirubinemia. The mechanism of bilirubin-induced neurotoxicity is not known. Many neurological insults are mediated through NMDA receptor activation.OBJECTIVE:
We assessed the effect of the NMDA channel antagonist, MK-801 on bilirubin neurotoxicity in vivo and in vitro.METHODS:
Bilirubin toxicity in vitro was assessed using trypan blue staining. Sulfadimethoxine injected (i.p.) jaundiced Gunn rat pups exhibit many neurological sequelae observed in human hyperbilirubinemia. Brainstem auditory-evoked potentials (BAEPs), a noninvasive sensitive tool to assess auditory dysfunction due to bilirubin neurotoxicity, were used to assess neuroprotection with MK-801 (i.p.) in vivo.RESULTS:
In primary cultures of hippocampal neurons, 20 min exposure to 6432 microM bilirubinhuman serum albumin reduced the cell viability by approximately 50% ten hours later. MK-801 treatment did not protect the cells. MK-801 pretreatment doses ranging from 0.1-4.0 mg/kg did not protect against BAEP abnormalities in Gunn rat pups 6 h after sulfadimethoxine injection.CONCLUSION:
Our findings suggest that bilirubin neurotoxicity is not mediated through NMDA receptor activation.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bilirrubina
/
Maleato de Dizocilpina
/
Receptores de N-Metil-D-Aspartato
/
Fármacos Neuroprotectores
/
Kernicterus
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neonatology
Asunto de la revista:
PERINATOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos