title: In-vivo detection of inflammation and neurodegeneration in the chronic phase after permanent embolic stroke in rats.
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, [(11)C]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 [(11)C]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.
authors.affiliation: Department of Neurology, University Hospital, Kerpener Str. 62, 50924 Cologne, Germany; Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Maureen
authors.initials: M
authors.lastname: Walberer
authors.affiliation: Department of Neurology, University Hospital, Kerpener Str. 62, 50924 Cologne, Germany; Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Sabine U
authors.initials: SU
authors.lastname: Jantzen
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Backes
authors.affiliation: Department of Neurology, University Hospital, Kerpener Str. 62, 50924 Cologne, Germany; Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rueger
authors.affiliation: Department of Neurology, University Hospital, Kerpener Str. 62, 50924 Cologne, Germany; Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Meike H
authors.initials: MH
authors.lastname: Keuters
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
authors.affiliation: Department of Neurology, University Hospital, Kerpener Str. 62, 50924 Cologne, Germany; Institute of Neuroscience and Medicine (INM-3), Cognitive Neuroscience, Research Centre Juelich, 52425 Juelich, Germany.
authors.forename: Gereon R
authors.initials: GR
authors.lastname: Fink
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Graf
authors.affiliation: Department of Neurology, University Hospital, Kerpener Str. 62, 50924 Cologne, Germany; Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Cologne, Germany. Electronic address: michael.schroeter@uk-koeln.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
mesh_terms: D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000503:physiopathology; D002250:Carbon Radioisotopes; D002908:Chronic Disease; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism; D007546:Isoquinolines; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000473:pathology / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D015213:Neuroimmunomodulation / Q000502:physiology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D017208:Rats, Wistar; D020521:Stroke / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000503:physiopathology
chemical_list: D000682:Amyloid; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D019275:Radiopharmaceuticals; D007501:Iron; C037850:PK 11195
keywords: Amyloid plaque; Macrosphere model; Microglia; Neuroinflammation; PK11195; Stroke