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@ARTICLE{Ladwig:863072,
author = {Ladwig, Anne and Rogall, Rebecca and Hucklenbroich, Jörg
and Willuweit, Antje and Schoeneck, Michael and Langen,
Karl-Josef and Fink, Gereon R. and Adele Rueger, M. and
Schroeter, Michael},
title = {{O}steopontin {A}ttenuates {S}econdary {N}eurodegeneration
in the {T}halamus after {E}xperimental {S}troke},
journal = {Journal of neuroImmune pharmacology},
volume = {14},
number = {2},
issn = {1557-1904},
address = {Boston, MA [u.a.]},
publisher = {Springer},
reportid = {FZJ-2019-03189},
pages = {295 - 311},
year = {2019},
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.},
cin = {INM-4 / INM-3},
ddc = {610},
cid = {I:(DE-Juel1)INM-4-20090406 / I:(DE-Juel1)INM-3-20090406},
pnm = {573 - Neuroimaging (POF3-573)},
pid = {G:(DE-HGF)POF3-573},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30488353},
UT = {WOS:000468351800011},
doi = {10.1007/s11481-018-9826-1},
url = {https://juser.fz-juelich.de/record/863072},
}