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Dantrolene protects neurons against kainic acid induced apoptosis in vitro and in vivo
Author(s) -
Popescu B. O.,
Oprica M.,
Sajin Maria,
Stanciu Cristina L.,
Bajenaru O.,
Predescu Andreea,
Vidulescu Cristina,
Popescu L. M.
Publication year - 2002
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2002.tb00454.x
Subject(s) - kainic acid , tunel assay , propidium iodide , apoptosis , status epilepticus , dna laddering , programmed cell death , terminal deoxynucleotidyl transferase , neuroprotection , biology , viability assay , in vivo , microbiology and biotechnology , pharmacology , biochemistry , receptor , neuroscience , glutamate receptor , epilepsy , dna fragmentation
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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