Dantrolene protects neurons against kainic acid induced apoptosis in vitro and in vivo.
Apoptotic cell death induced by kainic acid (KA) in cultures of rat cerebellar granule cells (CGC) and in different brain regions of Wistar rat pups on postnatal day 21 (P21) was studied. In vitro, KA (100-500 microM) induced a concentration-dependent loss of cell viability in MTT assay and cell death had apoptotic morphology as studied by chromatin staining with propidium iodide (PI). In vivo, twenty-four hours after induction of status epilepticus (SE) by an intraperitoneal KA injection (5 mg/kg) we quantified apoptotic cells in hippocampus (CA1 and CA3), parietal cortex and cerebellum using PI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique. We report that dantrolene, a specific ryanodine receptor antagonist, was able to significantly reduce the apoptotic cell death in CGC cultures and in hyppocampal CA1 and parietal cortex regions. Our finding can be valuable for neuroprotective therapy strategies in patients with repeated generalized seizures or status epilepticus.
Popescu
B O
BO
Department of Neurology, University Hospital, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania. Bogdan.Popescu@univermed-cdgm.ro
Oprica
M
M
Sajin
Maria
M
Stanciu
Cristina L
CL
Bajenaru
O
O
Predescu
Andreea
A
Vidulescu
Cristina
C
Popescu
L M
LM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D003620:Dantrolene / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007608:Kainic Acid / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D003620:Dantrolene; D007608:Kainic Acid