title: Cellular characterization of the peritumoral edema zone in malignant brain tumors.
abstract: Brain edema is a hallmark of human malignant brain tumors and contributes to the clinical course and outcome of brain tumor patients. The so-called perifocal edema or brain swelling imposes in T2-weighted MR scans as high intensity areas surrounding the bulk tumor mass. The mechanisms of this increased fluid attraction and the cellular composition of the microenvironment are only partially understood. In this study, we focus on imaging perifocal edema in orthotopically implanted gliomas in rodents and correlate perifocal edema with immunohistochemical markers. We identified that areas of perifocal edema not only include the tumor invasion zone, but also are associated with increased glial fibrillary acidic protein (GFAP) and aquaporin-4 expression surrounding the bulk tumor mass. Moreover, a high number of activated microglial cells expressing CD11b and macrophage migration inhibitory factor (MIF) accumulate at the tumor border. Thus, the area of perifocal edema is mainly dominated by reactive changes of vital brain tissue. These data corroborate that perifocal edema identified in T2-weighted MR scans are characterized with alterations in glial cell distribution and marker expression forming an inflammatory tumor microenvironment.
authors.affiliation: Department of Neuroradiology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Engelhorn
authors.forename: Nic E
authors.initials: NE
authors.lastname: Savaskan
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schwarz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kreutzer
authors.forename: Eric P
authors.initials: EP
authors.lastname: Meyer
authors.forename: Eric
authors.initials: E
authors.lastname: Hahnen
authors.forename: Oliver
authors.initials: O
authors.lastname: Ganslandt
authors.forename: Arnd
authors.initials: A
authors.lastname: Dörfler
authors.forename: Christopher
authors.initials: C
authors.lastname: Nimsky
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.forename: Ilker Y
authors.initials: IY
authors.lastname: Eyüpoglu
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000096:biosynthesis; D001929:Brain Edema / Q000209:etiology / Q000473:pathology*; D001932:Brain Neoplasms / Q000150:complications / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D005910:Glioma / Q000150:complications / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis; D008279:Magnetic Resonance Imaging; D017628:Microglia / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000150:complications / Q000473:pathology; D051381:Rats
chemical_list: D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515599:Mif protein, rat
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