Prevention of an increase in cortical ligand binding to AMPA receptors may represent a novel mechanism of endogenous brain protection by G-CSF after ischemic stroke

Abstract

Purpose: Using G-CSF deficient mice we recently demonstrated neuroprotective properties of endogenous G-CSF after ischemic stroke. The present follow-up study was designed to check, whether specific alterations in ligand binding densities of excitatory glutamate or inhibitory GABA_A receptors may participate in this effect.

Methods: Three groups of female mice were subjected to 45 minutes of MCAO: wildtype, G-CSF deficient and G-CSF deficient mice substituted with G-CSF. Infarct volumes were determined after 24 hours and quantitative in vitro receptor autoradiography was performed using [³H]MK-801, [³H]AMPA and [³H]muscimol for labeling of NMDA, AMPA and GABA_A receptors, respectively. Ligand binding densities were analyzed in regions in the ischemic core, peri-infarct areas and corresponding contralateral regions.

Results: Infarct volumes did not significantly differ between the experimental groups. Ligand binding densities of NMDA and GABA_A receptors were widely in the same range. However, AMPA receptor binding densities in G-CSF deficient mice were substantially enhanced compared to wildtype mice. G-CSF substitution in mice lacking G-CSF largely reversed this effect.

Conclusions: Although infarct volumes did not differ 24 hours after ischemia the increase of AMPA receptor binding densities in G-CSF deficient mice may explain the bigger infarcts previously observed at later time-points with the same stroke model.