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EVOluTION

ESR8

ESR 8: Rebecca Sienel

Rebecca.Sienel@med.uni-muenchen.de

Role of inhaled NO for neuroinflammation after ischemic stroke

Research project

Inhaled nitric oxide (iNO) reduces brain damage after cerebral ischemia (Terpolilli 2012, PMID: 22207711) but underlying mechanisms are yet unclear. Since NO inhibits the interaction of inflammatory cells with the endothelium in the systemic vasculature, ESR 8 will use state-of-the-art 3-D imaging technology to investigate the effect of iNO on leukocyte-endothelial interactions and on formation of monocyte microparticles in blood after stroke. Mice with fluorescent leukocyte subsets, e.g. LysM-GFP, Cx3CR1-GFP, CCR2-RFP, will be subjected to experimental stroke and cell adhesion to the cerebrovascular endothelium, transmigration from the vessel lumen across the blood-brain barrier, and migration and activation within the brain parenchyma will be visualized in 3D space in vivo by 2-PM microscopy and ex vivo by tissue clearing and high resolution light sheet microscopy. Plasma nitrite levels and monocyte microparticles will be measured in collaboration with QMUL.

Main Supervisor

Name: Nikolaus Plesnila
Email: nikolaus.plesnila@med.uni-muenchen.de

Host Institution

Institut für Schlaganfall- und Demenzforschung (ISD)
Klinikum der Universität München
Feodor-Lynen-Straße 17
81377 München
Germany

Expected Results

Establish the role of iNO as a novel therapeutic for cerebral ischemia and possibly other ischemic disorders and uncover the mechanisms underlying its neuroprotection. ESR 8 will be trained in the model of ischemic stroke in mice and to perform in vivo and ex vivo 3D brain imaging, i.e. investigate the interaction of inflammatory cells with cerebral vessels and brain parenchyma three-dimensionally without sectioning.

Planned secondment(s)

  1. QMUL, United Kingdom (September-November 2018): To measure monocyte microparticles in plasma of mice subjected to cerebral ischemia and chemoluminescence analysis for nitrite levels.
  2. WHRL, United Kingdom (December 2018): To train on design and draft of preclinical contract research.
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