NMDA blockade attenuates caspase-3 activation and DNA fragmentation after neonatal hypoxia-ischemia.
The aim was to study the effects of an NMDA receptor antagonist on caspase-3 activation and DNA fragmentation after hypoxia-ischemia (HI) in 7-day-old rats. Animals were treated with vehicle or MK-801 (0.5 mg/kg) directly after HI and sacrificed 8, 24 or 72h later. MK-801 reduced injury (by 53%), cells positive for active caspase-3 (by 39%) and DNA fragmentation (by 79%) in the cerebral cortex. Furthermore, MK-801 significantly decreased caspase-3 activity, and Western blots revealed a tendency towards decreased proteolytic cleavage of the caspase-3 proform. The data imply that NMDA receptors are involved in the activation of apoptotic processes in the immature brain after HI.
Puka-Sundvall
M
M
Perinatal Center, Department of Physiology, Göteborg University, Sweden.
Hallin
U
U
Zhu
C
C
Wang
X
X
Karlsson
J O
JO
Blomgren
K
K
Hagberg
H
H
D000818:Animals; D000831:Animals, Newborn / Q000293:injuries / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001238:Asphyxia Neonatorum / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D053938:DNA Fragmentation / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D007231:Infant, Newborn; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases