Journal Article

FZJ-2019-03189

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Osteopontin Attenuates Secondary Neurodegeneration in the Thalamus after Experimental Stroke

Ladwig, A. ; Rogall, R. ; Hucklenbroich, J. ; Willuweit, A.FZJ* ; Schoeneck, M. ; Langen, K.-J.FZJ* ; Fink, G. R.FZJ* ; Adele Rueger, M. ; Schroeter, M. (Corresponding author)

2019
Springer Boston, MA [u.a.]

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Please use a persistent id in citations: http://hdl.handle.net/2128/23174  doi:10.1007/s11481-018-9826-1

Abstract: Cortical cerebral ischemia elicits neuroinflammation as well as secondary neuronal degeneration in remote areas. Locally distinct and specific secondary neurodegeneration affecting thalamic nuclei connected to cortical areas highlights such processes. Osteopontin (OPN) is a cytokine-like glycoprotein that is excreted in high amounts after cerebral ischemia and exerts various immunomodulatory functions. We here examined putative protective effects of OPN in secondary thalamic degeneration. We subjected male Wistar rats to photothrombosis and subsequently injected OPN or placebo intracerebroventricularly. Immunohistochemical and fluorescence staining was used to detect the extent of neuronal degeneration and microglia activation. Ex vivo autoradiography with radiotracers available for human in vivo PET studies, i.e., cis-4-[18F]Fluor-d-Proline (D-cis-[18F]FPro), and [6-3H]thymidine ([3H]thymidine), confirmed degeneration and proliferation, respectively. We found secondary neurodegeneration in the thalamus characterized by microglial activation and neuronal loss. Neuronal loss was restricted to areas of microglial infiltration. Treatment with OPN significantly decreased neurodegeneration, inflammation and microglial proliferation. Microglia displayed morphological signs of activation without expressing markers of M1 or M2 polarization. D-cis-[18F]FPro-uptake mirrored attenuated degeneration in OPN-treated animals. Notably, [3H]thymidine and BrdU-staining revealed increased stem cell proliferation after treatment with OPN. The data suggest that OPN is able to ameliorate secondary neurodegeneration in thalamic nuclei. These effects can be visualized by radiotracers D-cis-[18F]FPro and [3H]thymidine, opening new vistas for translational studies.

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Contributing Institute(s):

1. Physik der Medizinischen Bildgebung (INM-4)
2. Kognitive Neurowissenschaften (INM-3)

Research Program(s):

1. 573 - Neuroimaging (POF3-573) (POF3-573)

Appears in the scientific report 2019

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Database coverage:
; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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