Universität zu Köln

Ladwig, Anne, Rogall, Rebecca, Hucklenbroich, Joerg, Willuweit, Antje, Schoeneck, Michael, Langen, Karl-Josef ORCID: 0000-0003-1101-5075, Fink, Gereon R. ORCID: 0000-0002-8230-1856, Rueger, M. Adele and Schroeter, Michael (2019). Osteopontin Attenuates Secondary Neurodegeneration in the Thalamus after Experimental Stroke. J. Neuroimmune Pharm., 14 (2). S. 295 - 312. NEW YORK: SPRINGER. ISSN 1557-1904

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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-[F-18]Fluor-d-Proline (D-cis-[F-18]FPro), and [6-H-3]thymidine ([H-3]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-[F-18]FPro-uptake mirrored attenuated degeneration in OPN-treated animals. Notably, [H-3]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-[F-18]FPro and [H-3]thymidine, opening new vistas for translational studies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ladwig, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Rogall, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucklenbroich, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Willuweit, Antje UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoeneck, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Langen, Karl-Josef UNSPECIFIED orcid.org/0000-0003-1101-5075 UNSPECIFIED Fink, Gereon R. UNSPECIFIED orcid.org/0000-0002-8230-1856 UNSPECIFIED Rueger, M. Adele UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-147306
DOI:	10.1007/s11481-018-9826-1
Journal or Publication Title:	J. Neuroimmune Pharm.
Volume:	14
Number:	2
Page Range:	S. 295 - 312
Date:	2019
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1557-1904
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NEURAL STEM-CELLS; IN-VITRO; PRIMARY MICROGLIA; BRAIN; RAT; MACROPHAGE; NEUROPROTECTION; EXPRESSION; ISCHEMIA; BINDING Multiple languages Neurosciences; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14730