Walberer, Maureen, Jantzen, Sabine U., Backes, Heiko, Rueger, Maria A., Keuters, Meilze H., Neumaier, Bernd ORCID: 0000-0001-5425-3116, Hoehn, Mathias, Fink, Gereon R. ORCID: 0000-0002-8230-1856, Graf, Rudolf and Schroeter, Michael (2014). In-vivo detection of inflammation and neurodegeneration in the chronic phase after permanent embolic stroke in rats. Brain Res., 1581. S. 80 - 89. AMSTERDAM: ELSEVIER. ISSN 1872-6240

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Abstract

Neuroinflammation with microglia activation (MA) constitutes a key tissue response in acute stroke. Until now, its course in the chronic stage is less well defined. Here, we investigated (i) neuroinflammation in the chronic stage of a rat model of embolic stroke (n=6), and (ii) whether this process can be visualized in vivo by multimodal imaging using Magnetic Resonance Imaging (MRI) and Positron-Emission-Tomography (PET). Imaging data were verified using histology and immunohistochemistry. Repetitive PET studies until week 6 after stroke reveal poststroke inflammation as a dynamic process that involved the infarct, the surrounding tissue and secondary degenerating areas in a complex fashion. At the end, 7 months after stroke, neuroinflammation had almost completely vanished at the lesion side. In contrast, remote from the primarily infarcted areas, a marked T2*- hypointensity was detected in the ipsilateral thalamus. In the corresponding area, [C-11]PK11195-PET detected microglia activation. Immunohistochemistry confirmed activated microglia in the ipsilateral thalamus with signs of extensive phagocytosis and iron deposition around plaque-like amyloid deposition. Neuronal staining (NeuN) revealed pronounced neuronal loss as an endpoint of neurodegeneration in these areas. In conclusion, the data demonstrate not only ongoing thalamic neuroinflammation but also marked neurodegeneration remote from the lesion site in the chronic phase after stroke in rats. Both, neuroinflammation and neurodegeneration were accessible to (immuno-) histochemical methods as well as to in vivo methods using [C-11]PK11195-PET and T2*-weighted MRI. Although the functional roles of these dynamic processes remain to be elucidated, ongoing destruction of neuronal tissue is conceivable. Its inhibition using anti-inflammatory substances may be beneficial in chronic post-stroke conditions, while multimodal imaging can be used to evaluate putative therapeutic effects in vivo. (C) 2014 Elsevier B.V. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Walberer, MaureenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jantzen, Sabine U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Backes, HeikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rueger, Maria A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keuters, Meilze H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumaier, BerndUNSPECIFIEDorcid.org/0000-0001-5425-3116UNSPECIFIED
Hoehn, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fink, Gereon R.UNSPECIFIEDorcid.org/0000-0002-8230-1856UNSPECIFIED
Graf, RudolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeter, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-428563
DOI: 10.1016/j.brainres.2014.05.030
Journal or Publication Title: Brain Res.
Volume: 1581
Page Range: S. 80 - 89
Date: 2014
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1872-6240
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CEREBRAL-ARTERY OCCLUSION; MICROGLIAL ACTIVATION; REFERENCE TISSUE; ISCHEMIC-STROKE; BRAIN; DEGENERATION; PET; NEUROINFLAMMATION; QUANTIFICATION; ACCUMULATIONMultiple languages
NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42856

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