A plethora of neurological disorders shares a final common deadly pathway known as excitotoxicity. Among these disorders, ischemic injury is a prominent cause of death and disability worldwide. Brain ischemia stems from cardiac arrest or stroke, both responsible for insufficient blood supply to the brain parenchyma. Glucose and oxygen deficiency disrupts oxidative phosphorylation, which results in energy depletion and ionic imbalance, followed by cell membrane depolarization, calcium (Ca2+) overload, and extracellular accumulation of excitatory amino acid glutamate. If tight physiological regulation fails to clear the surplus of this neurotransmitter, subsequent prolonged activation of glutamate receptors forms a vicious circle between elevated concentrations of intracellular Ca2+ ions and aberrant glutamate release, aggravating the effect of this ischemic pathway. The activation of downstream Ca2+-dependent enzymes has a catastrophic impact on nervous tissue leading to cell death, accompanied by the formation of free radicals, edema, and inflammation. After decades of "neuron-centric" approaches, recent research has also finally shed some light on the role of glial cells in neurological diseases. It is becoming more and more evident that neurons and glia depend on each other. Neuronal cells, astrocytes, microglia, NG2 glia, and oligodendrocytes all have their roles in what is known as glutamate excitotoxicity. However, who is the main contributor to the ischemic pathway, and who is the unsuspecting victim? In this review article, we summarize the so-far-revealed roles of cells in the central nervous system, with particular attention to glial cells in ischemia-induced glutamate excitotoxicity, its origins, and consequences.

• Klíčová slova
• NG2 glia, astrocytes, cell death, glutamate excitotoxicity, glutamate receptors and transporters, glutamate uptake/release, ischemic pathway, oligodendrocytes,
• Publikační typ
• časopisecké články MeSH

Cortical glial cells contain both ionotropic and metabotropic glutamate receptors. Despite several efforts, a comprehensive analysis of the entire family of glutamate receptors and their subunits present in glial cells is still missing. Here, we provide an overall picture of the gene expression of ionotropic (AMPA, kainate, NMDA) and the main metabotropic glutamate receptors in cortical glial cells isolated from GFAP/EGFP mice before and after focal cerebral ischemia. Employing single-cell RT-qPCR, we detected the expression of genes encoding subunits of glutamate receptors in GFAP/EGFP-positive (GFAP/EGFP(+)) glial cells in the cortex of young adult mice. Most of the analyzed cells expressed mRNA for glutamate receptor subunits, the expression of which, in most cases, even increased after ischemic injury. Data analyses disclosed several classes of GFAP/EGFP(+) glial cells with respect to glutamate receptors and revealed in what manner their expression correlates with the expression of glial markers prior to and after ischemia. Furthermore, we also examined the protein expression and functional significance of NMDA receptors in glial cells. Immunohistochemical analyses of all seven NMDA receptor subunits provided direct evidence that the GluN3A subunit is present in GFAP/EGFP(+) glial cells and that its expression is increased after ischemia. In situ and in vitro Ca(2+) imaging revealed that Ca(2+) elevations evoked by the application of NMDA were diminished in GFAP/EGFP(+) glial cells following ischemia. Our results provide a comprehensive description of glutamate receptors in cortical GFAP/EGFP(+) glial cells and may serve as a basis for further research on glial cell physiology and pathophysiology.

• Klíčová slova
• Astrocytes, Calcium imaging, MCAo, NG2 glia, Single-cell RT-qPCR,
• MeSH
• gliový fibrilární kyselý protein analýza   biosyntéza   MeSH
• glutamátové receptory analýza   biosyntéza   MeSH
• ischemie mozku metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mozková kůra chemie   metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• neuroglie chemie   metabolismus   MeSH
• receptory N-methyl-D-aspartátu analýza   biosyntéza   MeSH
• zelené fluorescenční proteiny analýza   biosyntéza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• enhanced green fluorescent protein MeSH Prohlížeč
• glial fibrillary astrocytic protein, mouse MeSH Prohlížeč
• gliový fibrilární kyselý protein MeSH
• glutamátové receptory MeSH
• receptory N-methyl-D-aspartátu MeSH
• zelené fluorescenční proteiny MeSH