gms | German Medical Science

63rd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Japanese Neurosurgical Society (JNS)

German Society of Neurosurgery (DGNC)

13 - 16 June 2012, Leipzig

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Neuroprotective effect of radical-containing nanoparticle (RNP) after cerebral ischemia-reperfusion injury

Meeting Abstract

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  • A. Marushima - Department of Neurosurgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
  • H. Tsurushima - Department of Neurosurgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
  • Y. Nagasaki - Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan
  • T. Yoshitomi - Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan
  • K. Toh - Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan
  • K. Suzuki - Department of Neurosurgery, Dokkyo Medical University Koshigaya Hospital, Minamikoshigaya, Japan
  • A. Hirayama - Center for Integrative Medicine, Tsukuba University of Technology, Tsukuba, Japan
  • A. Matsumura - Department of Neurosurgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocP 017

doi: 10.3205/12dgnc404, urn:nbn:de:0183-12dgnc4043

Published: June 4, 2012

© 2012 Marushima et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Neuroprotection is an essential treatment strategy for prevention of the ischemia-reperfusion injury, but a clinically available medicine is limited. Therefore, we developed a newly free radical sacavenger of core-shell-type nanoparticles (micelles) containing 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), termed a radical-containing nanoparticle (RNP), which had a prolonged half-life of TEMPO radicals and pH-sensitivity to make them act in the low pH condition such as ischemic lesion. (Yoshitomi, et.al. Biomacromolecules 2009). This time, we evaluated that the abilities of RNP to deliver TEMPO radicals in the ischemic brain and scavenge free radicals after cerebral ischemia-reperfusion injury using a transient cerebral ischemia model in rats.

Methods: The delivery of TEMPO radicals in RNP was evaluated by electron paramagnetic resonance (EPR) and fluorescence analysis. The production of superoxide anion in neuronal cells was examined by dihydroethidium staining. The treatment effects were evaluated by measuring the cerebral infarction volumes, evans blue extravasation, neurological symptom, lipid peroxidation and protein oxidation. The adverse events were evaluated with physiological parameters.

Results: The TEMPO radicals in RNPs were detected for 6 h after intravenous administration as an EPR signal in the ischemic brain, and distributed on the endothelial cells of the cerebral infarct area. RNPs significantly reduced superoxide anion in neuronal cells as compared to saline and TEMPOL. The infarct volume and extravasation of evans blue treated by RNPs were significantly lower than those of rats treated by saline, micelles, and TEMPOL. In addition, RNP treatment suppressed lipid peroxidation and protein oxidation, and limited the adverse effects of TEMPO radicals, such as hypotension.

Conclusions: RNPs could be a promising neuroprotective agent with the enhanced ability of TEMPO radicals and the reduced toxicity. (Marushima, et.al, Neurosurgery 2011)