Dantrolene protects neurons against kainic acid induced apoptosis in vitro and in vivo

• Published in: Journal of cellular and molecular medicine 2002-10, Vol.6 (4), p.555-569
• Main Authors: Popescu, B. O., Oprica, M., Sajin, Maria, Stanciu, Cristina L., Bajenaru, O., Predescu, Andreea, Vidulescu, Cristina, Popescu, L. M.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Brain - drug effects; Cell death; Cell viability; Cells, Cultured; cerebellar granule cells; Cerebellum; Chromatin; Cortex (parietal); Cytology; dantrolene; Dantrolene - pharmacology; DNA Damage - drug effects; DNA nucleotidylexotransferase; Dose-Response Relationship, Drug; Epilepsy; Granule cells; Kainic acid; Kainic Acid - pharmacology; Medicin och hälsovetenskap; Neurons - drug effects; Neurons - pathology; Neuroprotection; Propidium iodide; Rats; Rats, Wistar; ryanodine receptors; Seizures
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/j.1582-4934.2002.tb00454.x

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.