title: Dantrolene protects neurons against kainic acid induced apoptosis in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Neurology, University Hospital, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania. Bogdan.Popescu@univermed-cdgm.ro
authors.forename: B O
authors.initials: BO
authors.lastname: Popescu
authors.forename: M
authors.initials: M
authors.lastname: Oprica
authors.forename: Maria
authors.initials: M
authors.lastname: Sajin
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Stanciu
authors.forename: O
authors.initials: O
authors.lastname: Bajenaru
authors.forename: Andreea
authors.initials: A
authors.lastname: Predescu
authors.forename: Cristina
authors.initials: C
authors.lastname: Vidulescu
authors.forename: L M
authors.initials: LM
authors.lastname: Popescu
mesh_terms: 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
chemical_list: D003620:Dantrolene; D007608:Kainic Acid