Neuroprotective effects of agmatine on oxygen-glucose deprived primary-cultured astrocytes and nuclear translocation of nuclear factor-kappa B

Brain Res. 2009 Jul 24:1281:64-70. doi: 10.1016/j.brainres.2009.05.046. Epub 2009 May 22.

Abstract

To better understand the neuroprotective actions of agmatine in ischemic insults, its effects on astrocytes were investigated using an in vitro oxygen-glucose deprivation (OGD) model. After primary culture, cortical astrocytes were moved into a closed anaerobic chamber and incubated in glucose-free culture media. 4 h later, the cells were restored to normoxic conditions and supplied with glucose for 20 h. The ability of agmatine to rescue astrocytes from OGD only and OGD followed by restoration (OGD-R) was assessed. Cell viability was monitored with or without 100 muM agmatine, using the lactate dehydrogenase (LDH) assay and annexin V flow cytometric assay. For morphological analysis, Hoechst 33258 and propidium iodide double nuclear staining was performed. Expression and phosphorylation of nuclear factor-kappa B (NF-kappaB) family proteins were also investigated by immunoblotting. Results showed that astrocytes had decreased viability following OGD and OGD-R and that agmatine treatment increased cell viability and induced NF-kappaB translocation into the nucleus. Finally, our studies revealed that agmatine can rescue astrocytes from death caused by ischemic and/or ischemic-perfusion neuronal injuries in vitro. Our findings provide new insights that may lead to a novel therapeutic strategy to reduce these kinds of neuronal injuries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects*
  • Agmatine / pharmacology*
  • Animals
  • Annexin A5 / metabolism
  • Astrocytes / cytology
  • Astrocytes / drug effects*
  • Astrocytes / physiology*
  • Bisbenzimidazole
  • Blotting, Western
  • Cell Hypoxia / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology
  • Flow Cytometry
  • Glucose / deficiency
  • Glucose / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / metabolism*
  • Neuroprotective Agents / pharmacology*
  • Phosphorylation / drug effects
  • Propidium

Substances

  • Annexin A5
  • NF-kappa B
  • Neuroprotective Agents
  • Propidium
  • Agmatine
  • L-Lactate Dehydrogenase
  • Glucose
  • Bisbenzimidazole