title: Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats.
abstract: Cerebral inflammation plays a crucial role in the pathophysiology of ischemic stroke and is involved in all stages of the ischemic cascade. Fullerene derivatives, such as fullerenol (OH-F) are radical scavengers acting as neuroprotective agents while glucosamine (GlcN) attenuates cerebral inflammation after stroke. We created novel glucosamine-fullerene conjugates (GlcN-F) to combine their protective effects and compared them to OH-F regarding stroke-induced cerebral inflammation and cellular damage. Fullerene derivatives or vehicle was administered intravenously in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) immediately after transient middle cerebral artery occlusion (tMCAO). Infarct size was determined at day 5 and neurological outcome at days 1 and 5 after tMCAO. CD68- and NeuN-staining were performed to determine immunoreactivity and neuronal survival respectively. Cytokine and toll like receptor 4 (TLR-4) expression was assessed using quantitative real-time PCR. Magnetic resonance imaging revealed a significant reduction of infarct volume in both, WKY and SHR that were treated with fullerene derivatives. Treated rats showed an amelioration of neurological symptoms as both OH-F and GlcN-F prevented neuronal loss in the perilesional area. Cerebral immunoreactivity was reduced in treated WKY and SHR. Expression of IL-1β and TLR-4 was attenuated in OH-F-treated WKY rats. In conclusion, OH-F and GlcN-F lead to a reduction of cellular damage and inflammation after stroke, rendering these compounds attractive therapeutics for stroke.
authors.affiliation: Department of Neurology, University Hospital Zürich, 8091 Zürich, Switzerland; Department of Neurology, University Hospital Basel, 4031 Basel, Switzerland. Electronic address: felix.fluri@gmx.ch.
authors.forename: Felix
authors.initials: F
authors.lastname: Fluri
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute for Chemistry and Biology, Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Grünstein
authors.affiliation: Department of Neurology, University Hospital Zürich, 8091 Zürich, Switzerland.
authors.forename: Ertugrul
authors.initials: E
authors.lastname: Cam
authors.affiliation: Department of Surgery, Swiss Hepato-Pancreatico-Biliary Center, University Hospital Zürich, 8091 Zürich, Switzerland.
authors.forename: Udo
authors.initials: U
authors.lastname: Ungethuem
authors.affiliation: Department of Neurology, University Hospital Basel, 4031 Basel, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Hatz
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, 4031 Basel, Switzerland.
authors.forename: Juliane
authors.initials: J
authors.lastname: Schäfer
authors.affiliation: Department of Nuclear Medicine, Interdisciplinary PET Center, University Hospital Würzburg, 97080 Würzburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Samnick
authors.affiliation: Department of Nuclear Medicine, Interdisciplinary PET Center, University Hospital Würzburg, 97080 Würzburg, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Israel
authors.affiliation: Department of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute for Chemistry and Biology, Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Orts-Gil
authors.affiliation: Institute for Surgical Pathology, Department of Pathology and Laboratory Medicine, University Hospital Zürich, 8091 Zürich, Switzerland.
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.affiliation: Neurobiology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zeis
authors.affiliation: Neurobiology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schaeren-Wiemers
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute for Chemistry and Biology, Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Seeberger
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D037741:Fullerenes / Q000008:administration & dosage*; D005944:Glucosamine / Q000008:administration & dosage*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
chemical_list: D037741:Fullerenes; C108127:fullerenol; D005944:Glucosamine
keywords: Animal experiments; Fullerene; Inflammation; Ischemic stroke; Neuroprotective agents