Ethyl pyruvate does not require microglia for mediating neuroprotection after excitotoxic injury.
CNS Neurosci Ther
; 23(10): 798-807, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28836378
ABSTRACT
AIMS:
Ethyl pyruvate (EP) mediates protective effects after neuronal injury. Besides a direct conservation of damaged neurons, the modulation of indigenous glial cells has been suggested as one important mechanism for EP-related neuroprotection. However, the specific contribution of glial cells is still unknown.METHODS:
Organotypic hippocampal slice cultures (OHSC) were excitotoxically lesioned by 50 µmol/L N-methyl-D-aspartate (NMDA, for 4 hours) or left untreated. In an additional OHSC subset, microglia was depleted using the bisphosphonate clodronate (100 µg/mL) before lesion. After removal of NMDA, EP containing culture medium (0.84 µmol/L, 8.4 µmol/L, 42 µmol/L, 84 µmol/L, 168 µmol/L) was added and incubated for 72 hours. OHSC were stained with propidium iodide to visualize degenerating neurons and isolectin IB4 -FITC to identify microglia. Effects of EP at concentrations of 0.84, 8.4, and 84 µmol/L (0-48 hours) were analyzed in the astrocytic scratch wound assay.RESULTS:
EP significantly reduced neurodegeneration following induced excitotoxicity except for 168 µmol/L. For 84 µmol/L, a reduction in the microglia cells was observed. Microglia depletion did not affect neuronal survival after EP treatment. EP decelerated astrocytic wound closure at 48 hours after injury.CONCLUSION:
EP-mediated neuroprotection seems to be mediated by astrocytes and/or neurons.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piruvatos
/
Microglia
/
Fármacos Neuroprotetores
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
CNS Neurosci Ther
Assunto da revista:
NEUROLOGIA
/
TERAPEUTICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Alemanha