title: 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: 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 GABAA receptors may participate in this effect.
  
  
  
  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 GABAA receptors, respectively. Ligand binding densities were analyzed in regions in the ischemic core, peri-infarct areas and corresponding contralateral regions.
  
  
  
  Infarct volumes did not significantly differ between the experimental groups. Ligand binding densities of NMDA and GABAA 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.
  
  
  
  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.
authors.affiliation: Institute of Neuropathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mammele
authors.affiliation: Institute of Neuropathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Frauenknecht
authors.affiliation: Department of Neurology, University of Münster, Germany.
authors.forename: Sevgi
authors.initials: S
authors.lastname: Sevimli
authors.affiliation: Department of Neurology, University of Münster, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Diederich
authors.affiliation: Institute of Neuropathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Bauer
authors.affiliation: Institute of Neuropathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Grimm
authors.affiliation: Department of Neurology, University of Münster, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Minnerup
authors.affiliation: Department of Neurology, University of Münster, Germany.|Neurology, Bethel, EVKB, Bielefeld, Germany.
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
authors.affiliation: Institute of Neuropathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Clemens J
authors.initials: CJ
authors.lastname: Sommer
mesh_terms: D000818:Animals; D001345:Autoradiography; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D000066829:Neuroprotection / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D020521:Stroke / Q000378:metabolism* / Q000473:pathology*
chemical_list: D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D016179:Granulocyte Colony-Stimulating Factor
keywords: AMPA; G-CSF; MCAO; autoradiography; excitotoxicity; focal ischemia; infarct volume; mouse