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

Fluri, F., Grünstein, D., Cam, E., Ungethuem, U., Hatz, F., Schäfer, J., et al. (2015). Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats. Experimental Neurology, 265, 142-151. doi:10.1016/j.expneurol.2015.01.005.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-0026-B810-7 Version Permalink: https://hdl.handle.net/21.11116/0000-0007-E351-D
Genre: Journal Article

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 Creators:
Fluri, Felix, Author
Grünstein, Dan1, Author           
Cam, Ertugrul, Author
Ungethuem, Udo, Author
Hatz, Florian, Author
Schäfer, Juliane, Author
Samnick, Samuel, Author
Israel, Ina, Author
Kleinschnitz, Christoph, Author
Orts-Gil, Giullermo2, Author           
Moch, Holger, Author
Zeis, Thomas, Author
Schaeren-Wiemers, Nicole, Author
Seeberger, Peter H.3, Author           
Affiliations:
1Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863286              
2Peter H. Seeberger - Nanoparticles and Colloidal Polymers, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863307              
3Peter H. Seeberger - Automated Systems, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863306              

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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.

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 Dates: 2015-01-242015
 Publication Status: Issued
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 Identifiers: ISI: 000351021900015
DOI: 10.1016/j.expneurol.2015.01.005
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Title: Experimental Neurology
  Other : Exp. Neurol.
Source Genre: Journal
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Publ. Info: San Diego, CA : Academic Press
Pages: - Volume / Issue: 265 Sequence Number: - Start / End Page: 142 - 151 Identifier: ISSN: 0014-4886