Caroline Vandeputte
Bioluminescence imaging of stroke-induced endogenous neural stem cell response
Vandeputte, Caroline; Reumers, Veerle; Aelvoet, Sarah-Ann; Thiry, Irina; De Swaef, Sylvie; Van den Haute, Chris; Pascual-Brazo, Jesus; Farr, Tracy D.; Vande Velde, Greetje; Hoehn, Mathias; Himmelreich, Uwe; Van Laere, Koen; Debyser, Zeger; Gijsbers, Rik; Baekelandt, Veerle
Authors
Veerle Reumers
Sarah-Ann Aelvoet
Irina Thiry
Sylvie De Swaef
Chris Van den Haute
Jesus Pascual-Brazo
Tracy D. Farr
Greetje Vande Velde
Mathias Hoehn
Uwe Himmelreich
Koen Van Laere
Zeger Debyser
Rik Gijsbers
Veerle Baekelandt
Abstract
Brain injury following stroke affects neurogenesis in the adult mammalian brain. However, a complete under¬standing of the origin and fate of the endogenous neural stem cells (eNSCs) in vivo is missing. Tools and technol¬ogy that allow non-invasive imaging and tracking of eNSCs in living animals will help to overcome this hurdle. In this study, we aimed to monitor eNSCs in a photothrombotic (PT) stroke model using in vivo bioluminescence imaging (BLI). In a first strategy, inducible transgenic mice expressing firefly luciferase (Fluc) in the eNSCs were generated. In animals that received stroke, an increased BLI signal originating from the infarct region was ob¬served. However, due to histological limitations, the identity and exact origin of cells contributing to the in¬creased BLI signal could not be revealed. To overcome this limitation, we developed an alternative strategy employing stereotactic injection of conditional lentiviral vectors (Cre-Flex LVs) encoding Fluc and eGFP in the subventricular zone (SVZ) of Nestin-Cre transgenic mice, thereby specifically labeling the eNSCs. Upon induction of stroke, increased eNSC proliferation resulted in a significant increase in BLI signal between 2 days and 2 weeks after stroke, decreasing after 3 months. Additionally, the BLI signal relocalized from the SVZ towards the infarct region during the 2 weeks following stroke. Histological analysis at 90 days post stroke showed that in the peri-infarct area, 36% of labeled eNSC progeny differentiated into astrocytes, while 21% differentiated into mature neu¬rons. In conclusion, we developed and validated a novel imaging technique that unequivocally demonstrates that nestin+ eNSCs originating from the SVZ respond to stroke injury by increased proliferation, migration towards the infarct region and differentiation into both astrocytes and neurons. In addition, this new approach allows non-invasive and specific monitoring of eNSCs overtime, opening perspectives for preclinical evaluation of can¬didate stroke therapeutics.
Citation
Vandeputte, C., Reumers, V., Aelvoet, S.-A., Thiry, I., De Swaef, S., Van den Haute, C., …Baekelandt, V. (2014). Bioluminescence imaging of stroke-induced endogenous neural stem cell response. Neurobiology of Disease, 69, https://doi.org/10.1016/j.nbd.2014.05.014
Journal Article Type | Article |
---|---|
Acceptance Date | May 17, 2014 |
Online Publication Date | May 27, 2014 |
Publication Date | Sep 1, 2014 |
Deposit Date | Apr 28, 2016 |
Publicly Available Date | Apr 28, 2016 |
Journal | Neurobiology of Disease |
Print ISSN | 0969-9961 |
Electronic ISSN | 1095-953X |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 69 |
DOI | https://doi.org/10.1016/j.nbd.2014.05.014 |
Keywords | Bioluminescence imaging; Cre-Flex lentiviral vector; Endogenous neural stem cells; Nestin-Cre mice; Stroke |
Public URL | https://nottingham-repository.worktribe.com/output/733473 |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S0969996114001326 |
Contract Date | Apr 28, 2016 |
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0
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