Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation.
Some anticonvulsants show neuroprotective effects, and may be of use in reducing neuronal death resulting from stroke or traumatic brain injury. Here I report that a broad range of anticonvulsants protect cells in hippocampal slice cultures from death induced by oxygen/glucose deprivation (OGD). Hippocampal slice cultures were submitted to 1 h OGD and the resulting cell death was quantified 24 h later using a novel automated fluorescent scanning method. The classical anticonvulsants phenobarbital, phenytoin, ethosuximide, chlordiazepoxide and midazolam all significantly and dose-dependently reduced cell death induced by OGD. The newer anticonvulsants carbamazepine, felbamate, lamotrigine, tiagabine, and oxcarbazepine also had significant neuroprotective effects, but gabapentin, valproic acid (10 mM), levetiracetam and retigabine were not neuroprotective at a concentration up to 300 microM. In conclusion, several classical and newer anticonvulsants have neuroprotective properties in an in vitro model that simulates cerebral ischemia.
Rekling
Jens C
JC
H. Lundbeck A/S, Biological Research, Department 828, Ottiliavej 9, DK-2500 Valby, Denmark. jre@lundbeck.com
D000085:Acetates / Q000494:pharmacology; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002707:Chlordiazepoxide / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids; D004305:Dose-Response Relationship, Drug; D005013:Ethosuximide / Q000494:pharmacology; D000078328:Felbamate; D000077206:Gabapentin; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism; D000077213:Lamotrigine; D000077287:Levetiracetam; D008874:Midazolam / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology; D000078330:Oxcarbazepine; D010634:Phenobarbital / Q000494:pharmacology; D048448:Phenylcarbamates; D010655:Phenylenediamines / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D011409:Propylene Glycols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000078308:Tiagabine; D014227:Triazines / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D002219:Carbamates; D003509:Cyclohexanecarboxylic Acids; D018696:Neuroprotective Agents; D009557:Nipecotic Acids; D048448:Phenylcarbamates; D010655:Phenylenediamines; D011409:Propylene Glycols; D014227:Triazines; C101866:ezogabine; D002220:Carbamazepine; D000077287:Levetiracetam; D005680:gamma-Aminobutyric Acid; D005013:Ethosuximide; D014635:Valproic Acid; D010672:Phenytoin; D000077206:Gabapentin; D002707:Chlordiazepoxide; D005947:Glucose; D008874:Midazolam; D000077213:Lamotrigine; D000078330:Oxcarbazepine; D000078328:Felbamate; D010634:Phenobarbital; D000078308:Tiagabine; D010889:Piracetam