Reactive astrocytes and activated microglial cells express EAAT1, but not EAAT2, reflecting a neuroprotective potential following ischaemia
- 31 May 2007
- journal article
- Published by Wiley in Histopathology
- Vol. 50 (7), 897-910
- https://doi.org/10.1111/j.1365-2559.2007.02703.x
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 and results: 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.Keywords
This publication has 38 references indexed in Scilit:
- Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transportNeurobiology of Disease, 2005
- Lipopolysaccharide increases microglial GLT‐1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF‐αGlia, 2005
- β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expressionNature, 2005
- Glial glutamate transporter expression patterns in brains from multiple mammalian speciesGlia, 2004
- Attenuation of a delayed increase in the extracellular glutamate level in the peri-infarct area following focal cerebral ischemia by a novel agent ONO-2506Neurochemistry International, 2004
- Expression of excitatory amino acid transporter‐2 (EAAT‐2) and glutamine synthetase (GS) in brain macrophages and microglia of SIVmac251‐infected macaquesNeuropathology and Applied Neurobiology, 2002
- Glutamate uptakeProgress in Neurobiology, 2001
- Clinical trials with neuroprotective drugs in acute ischaemic stroke: are we doing the right thing?Trends in Neurosciences, 1999
- Kinetics of a human glutamate transporterNeuron, 1995
- Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptakeNature, 1990