Phenytoin protects against hypoxia-induced death of cultured hippocampal neurons.
The neuroprotective actions of the anticonvulsant phenytoin (diphenylhydantoin, PHT) were evaluated using 3 week old primary hippocampal cultures derived from 19 day embryonic rat. When added to the culture medium prior to a hypoxic insult, PHT increased neuronal viability two-fold. Doubling extracellular Mg2+ concentration was similarly neuroprotective. In contrast, PHT was unable to protect against hypoxia-induced death in one week old cultures, nor was PHT protective against N-methyl-D-aspartate (NMDA)-induced neurotoxicity in cultures of either age. These findings suggest that non-NMDA receptor mechanisms are important in hypoxia-induced neuronal death, and may have important implications for the treatment of stroke.
Boehm
F H
FH
Department of Neurosurgery, Albert Einstein College of Medicine, Bronx, NY 10461.
Liem
L K
LK
Stanton
P K
PK
Potter
P E
PE
Moskal
J R
JR
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence; D046508:Culture Techniques / Q000295:instrumentation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D006624:Hippocampus / Q000166:cytology*; D008274:Magnesium / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats
D010672:Phenytoin; D016202:N-Methylaspartate; D008274:Magnesium