title: Lack of functional P2X7 receptor aggravates brain edema development after middle cerebral artery occlusion.
abstract: Effective therapeutic measures against the development of brain edema, a life-threatening complication of cerebral ischemia, are necessary to improve the functional outcome for the patient. Here, we identified a beneficial role of purinergic receptor P2X7 activation in acute ischemic stroke. Involvement of P2X7 in the development of neurological deficits, infarct size, brain edema, and glial responses after ischemic cerebral infarction has been analyzed. Neurologic evaluation, magnetic resonance imaging, and immunofluorescence assays were used to characterize the receptor's effect on the disease progress during 72 h after transient middle cerebral artery occlusion (tMCAO). Sham-operated animals were included in all experiments for control purposes. We found P2X7-deficient mice to develop a more prominent brain edema with a trend towards more severe neurological deficits 24 h after tMCAO. Infarct sizes, T2 times, and apparent diffusion coefficients did not differ significantly between wild-type and P2X7(-/-) animals. Our results show a characteristic spatial distribution of reactive glia cells with strongly attenuated microglia activation in P2X7(-/-) mice 72 h after tMCAO. Our data indicate that P2X7 exerts a role in limiting the early edema formation, possibly by modulating glial responses, and supports later microglia activation.
authors.affiliation: Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Universität Leipzig, Härtelstr. 16-18, 04107, Leipzig, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Institute of Medical Physics and Biophysics, Medical Faculty, Universität Leipzig, Leipzig, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Penk
authors.affiliation: Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Universität Leipzig, Härtelstr. 16-18, 04107, Leipzig, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Franke
authors.affiliation: Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Universität Leipzig, Härtelstr. 16-18, 04107, Leipzig, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Krügel
authors.affiliation: Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Universität Leipzig, Härtelstr. 16-18, 04107, Leipzig, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nörenberg
authors.affiliation: Institute of Medical Physics and Biophysics, Medical Faculty, Universität Leipzig, Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Huster
authors.affiliation: Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Universität Leipzig, Härtelstr. 16-18, 04107, Leipzig, Germany. michael.schaefer@medizin.uni-leipzig.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Schaefer
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*
chemical_list: D058486:Receptors, Purinergic P2X7
keywords: Brain ischemia; MCAO; Microglia; P2X7; Purinergic receptor