Neonatology · 2007
NMDA channel antagonist MK-801 does not protect against bilirubin neurotoxicity.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shapiro Steven M, Sombati Sompong, Geiger Angela, Rice Ann C
Аннотация
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 64:32 microM bilirubin:human 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.
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 64:32 microM bilirubin:human 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.
Предметные рубрики MeSH
AnimalsAnimals, NewbornAnti-Infective AgentsBilirubinCell SurvivalDisease Models, AnimalDizocilpine MaleateDose-Response Relationship, DrugEvoked Potentials, Auditory, Brain StemHyperbilirubinemiaJaundiceKernicterusNeuronsNeuroprotective AgentsRatsRats, GunnReceptors, N-Methyl-D-AspartateSulfadimethoxine