Bioluminescence imaging of stroke-induced endogenous neural stem cell response
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 wil...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
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Elsevier
2014
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| Online Access: | https://eprints.nottingham.ac.uk/32989/ |
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| author | 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 |
| author_facet | 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 |
| author_sort | Vandeputte, Caroline |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:17:43Z |
| format | Article |
| id | nottingham-32989 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:17:43Z |
| publishDate | 2014 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-329892020-05-04T16:51:49Z https://eprints.nottingham.ac.uk/32989/ 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 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. Elsevier 2014-09-01 Article PeerReviewed 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 and Baekelandt, Veerle (2014) Bioluminescence imaging of stroke-induced endogenous neural stem cell response. Neurobiology of Disease, 69 . pp. 144-155. ISSN 1095-953X Bioluminescence imaging; Cre-Flex lentiviral vector; Endogenous neural stem cells; Nestin-Cre mice; Stroke http://www.sciencedirect.com/science/article/pii/S0969996114001326 doi:10.1016/j.nbd.2014.05.014 doi:10.1016/j.nbd.2014.05.014 |
| spellingShingle | Bioluminescence imaging; Cre-Flex lentiviral vector; Endogenous neural stem cells; Nestin-Cre mice; Stroke 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 Bioluminescence imaging of stroke-induced endogenous neural stem cell response |
| title | Bioluminescence imaging of stroke-induced endogenous neural stem cell response |
| title_full | Bioluminescence imaging of stroke-induced endogenous neural stem cell response |
| title_fullStr | Bioluminescence imaging of stroke-induced endogenous neural stem cell response |
| title_full_unstemmed | Bioluminescence imaging of stroke-induced endogenous neural stem cell response |
| title_short | Bioluminescence imaging of stroke-induced endogenous neural stem cell response |
| title_sort | bioluminescence imaging of stroke-induced endogenous neural stem cell response |
| topic | Bioluminescence imaging; Cre-Flex lentiviral vector; Endogenous neural stem cells; Nestin-Cre mice; Stroke |
| url | https://eprints.nottingham.ac.uk/32989/ https://eprints.nottingham.ac.uk/32989/ https://eprints.nottingham.ac.uk/32989/ |