Dantrolene protects neurons against kainic acid induced apoptosis in vitro and in vivo |
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Authors: | Popescu B O Oprica M Sajin Maria Stanciu Cristina L Bajenaru O Predescu Andreea Vidulescu Cristina Popescu L M |
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Institution: | Department of Neurology, University Hospital, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania;"Victor Babes" National Institute of Pathology, Bucharest, Romania;Neurotec, Section of Experimental Geriatrics, KFC, NOVUM, Karolinska Institutet, Stockholm, Sweden;Department of Pathology, University Hospital, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania;Division of Cellular and Molecular Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania |
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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 μM) 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. |
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Keywords: | apoptosis epilepsy kainic acid dantrolene ryanodine receptors cerebellar granule cells |
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