PMID- 17556843
OWN - NLM
STAT- MEDLINE
DCOM- 20071210
LR  - 20131121
IS  - 1661-7819 (Electronic)
IS  - 1661-7800 (Linking)
VI  - 92
IP  - 4
DP  - 2007
TI  - NMDA channel antagonist MK-801 does not protect against bilirubin neurotoxicity.
PG  - 248-57
AB  - 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.
CI  - (c) 2007 S. Karger AG, Basel.
FAU - Shapiro, Steven M
AU  - Shapiro SM
AD  - Department of Neurology, Virginia Commonwealth University, Richmond, VA 
      23298-0599, USA.
FAU - Sombati, Sompong
AU  - Sombati S
FAU - Geiger, Angela
AU  - Geiger A
FAU - Rice, Ann C
AU  - Rice AC
LA  - eng
GR  - R01 DC00369/DC/NIDCD NIH HHS/United States
GR  - R01 NS47151/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070608
PL  - Switzerland
TA  - Neonatology
JT  - Neonatology
JID - 101286577
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 30CPC5LDEX (Sulfadimethoxine)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Anti-Infective Agents
MH  - Bilirubin/*adverse effects
MH  - Cell Survival/drug effects/physiology
MH  - Disease Models, Animal
MH  - Dizocilpine Maleate/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Evoked Potentials, Auditory, Brain Stem/drug effects/physiology
MH  - Hyperbilirubinemia/chemically induced/complications/physiopathology
MH  - Jaundice/chemically induced/complications/physiopathology
MH  - Kernicterus/etiology/physiopathology/*prevention & control
MH  - Neurons/drug effects/physiology
MH  - Neuroprotective Agents/*pharmacology
MH  - Rats
MH  - Rats, Gunn
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/physiology
MH  - Sulfadimethoxine
EDAT- 2007/06/09 09:00
MHDA- 2007/12/11 09:00
CRDT- 2007/06/09 09:00
PHST- 2006/11/07 00:00 [received]
PHST- 2007/02/05 00:00 [accepted]
PHST- 2007/06/09 09:00 [pubmed]
PHST- 2007/12/11 09:00 [medline]
PHST- 2007/06/09 09:00 [entrez]
AID - 000103743 [pii]
AID - 10.1159/000103743 [doi]
PST - ppublish
SO  - Neonatology. 2007;92(4):248-57. doi: 10.1159/000103743. Epub 2007 Jun 8.