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Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats

Fluri, Felix and Grünstein, Dan and Cam, Ertugrul and Ungethuem, Udo and Hatz, Florian and Schäfer, Juliane and Samnick, Samuel and Israel, Ina and Kleinschnitz, Christoph and Orts-Gil, Guillermo and Moch, Holger and Zeis, Thomas and Schaeren-Wiemers, Nicole and Seeberger, Peter. (2015) Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats. Experimental Neurology, 265. pp. 142-151.

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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.
Faculties and Departments:03 Faculty of Medicine
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Neurobiology (Schaeren-Wiemers)
UniBasel Contributors:Schaeren-Wiemers, Nicole and Zeis, Thomas
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0014-4886
e-ISSN:0014-4886
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:04 Dec 2017 11:13
Deposited On:04 Dec 2017 11:13

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