Reactive astrocytes and activated microglial cells express EAAT1, but not EAAT2, reflecting a neuroprotective potential following ischaemia.
Histopathology
; 50(7): 897-910, 2007 Jun.
Article
em En
| MEDLINE
| ID: mdl-17543080
ABSTRACT
AIMS:
Glutamate receptor antagonists have failed clinical stroke trials and it has been proposed that the action of N-methyl D-aspartate receptors is necessary for neuronal survival. Thus, excitatory amino acid transporters (EAATs) might be a promising therapeutic target. The aim of this study was to investigate glial expression of EAATs following ischaemia. METHODS ANDRESULTS:
Expression of EAAT1 (GLAST) and EAAT2 (Glt-1) in 24 cases of ischaemia was examined by immunohistochemistry. Cortical expression of both EAATs in the lesion decreased within 24 h (P < 0.01, each). Whereas EAAT1+ white matter cells increased 18-fold (P < 0.05) within 24 h in the lesion and remained elevated for months in adjacent (469-fold, P < 0.01) and remote areas (20-fold, P < 0.05), EAAT2+ white matter cells were equivalent in ischaemia and controls. In the first week after stroke mainly activated (ramified and amoeboid) microglia expressed EAAT1, whereas monocytic cells in perivascular spaces and foamy macrophages lacked EAAT1. After more than 1 week, predominantly reactive astrocytes expressed EAAT1.CONCLUSIONS:
Microglial EAAT1 expression is restricted to the early/intermediate stage of activation and blood-derived (perivascular) monocytes do not contribute to EAAT1+ cells following ischaemia. Whether a pharmacological increase in glial EAAT expression may compensate for loss of cortical EAAT expression and reduce neuronal damage following stroke requires investigation by further functional studies.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Isquemia Encefálica
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Astrócitos
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Microglia
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Fármacos Neuroprotetores
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Transportador 1 de Aminoácido Excitatório
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Proteínas de Transporte de Glutamato da Membrana Plasmática
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Histopathology
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Alemanha
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM