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Frontiers in Neurology


Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2018.01014


  • 1Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy of Craiova, Romania
  • 2Laboratory of Molecular Biology and Pathology Research, Bucharest University Emergency Hospital, Romania
  • 3Department of Neurology, University Hospital Essen, Germany
  • 4School of Medicine, Griffith Health, Griffith University, Australia

Despite the obvious clinical significance of post-stroke angiogenesis, a detailed microscopic analysis of pre-stroke vascular remodeling and post-stroke angiogenesis has not yet been undertaken in an experimental model. In this study, using BrdU-labelling of proliferating cells and immunofluorescence of pre- and post-stroke rats, we found that (i) BrdU administered before stroke was incorporated preferentially into the nuclei of endothelial cells lining the lumen of existing blood vessels and newly born neurons in the dentate gyrus but not in the subventricular zone or proliferating microglia. (ii) BrdU injection prior stroke led to the patchy distribution of newly incorporated endothelial cells in existing blood vessels of the adult rat brain. (iii) BrdU injection prior stroke specifically labelled neuronal precursors cells in the region beyond the inhibitory scar region which seems to be permissive to regenerative events. (iv) BrdU injection after stroke led to the labelling of endothelial cells crossing or detaching from the disintegrating blood vessels, and their incorporation into new blood vessels in the stroke region, scar tissue and the region beyond. (v) BrdU injection after stroke led to the specific incorporation of BrdU+ nuclei into the “pinwheel” architecture of the ventricular epithelium. (vi) Blood vessels in remote areas of the infarct core and in the contralateral non-lesioned cortex, showed co-labelled BrdU/RECA+ endothelial cells shortly after the BrdU injection, which strongly suggests a bone marrow origin of the endothelial cells. In the damaged cortex, a BrdU/P4Hß double labeling in close proximity of collagen IV-labelled basement membrane suggests that, in addition to bone marrow derived endothelial cells, the disintegrating vascular wall itself could also be a source of proliferating endothelial cells. (vii) By day 28 after the stroke, new blood vessels were emerging in the perinfarcted area and the scar tissue region, which is generally resistant to regenerative events. Finally, beyond the inhibitory fibrotic scar, in a region of soft tissue that we dubbed “islet of regeneration”, vigorous angiogenesis was also detected.
Conclusion: BrdU administered before and after stroke allows the detection of specific brain vasculature remodelling.

Keywords: Stroke, Angiogenensis, remodelling, BrdU-labelling, Endothelial cells (EC)

Received: 20 Sep 2018; Accepted: 09 Nov 2018.

Edited by:

Mark P. Burns, Georgetown University, United States

Reviewed by:

Johannes Boltze, Fraunhofer-Institut für Zelltherapie und Immunologie (IZI), Germany
Jukka Jolkkonen, University of Eastern Finland, Finland  

Copyright: © 2018 Surugiu, Glavan, Popescu, Margaritescu, Eugen and Popa-Wagner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Aurel Popa-Wagner, Department of Neurology, University Hospital Essen, Essen, Germany,