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Injury-Transplantation Interval-Dependent Amelioration of Axonal Degeneration and Motor Deficit in Rats with Penetrating Traumatic Brain Injury

Penetrating traumatic brain injury (pTBI) is increasingly survivable, but permanently disabling as adult mammalian nervous system does not regenerate. Recently, our group demonstrated transplant location-dependent neuroprotection and safety of clinical trial–grade human neural stem cell (hNSC) trans...

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Autores principales: Andreu, MaryLourdes, Sanchez, Liz M. Quesada, Spurlock, Markus S., Hu, Zhen, Mahavadi, Anil, Powell, Henry R., Lujan, Maria M., Nodal, Samuel, Cera, Melissa, Ciocca, Isabella, Bullock, Ross, Gajavelli, Shyam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122235/
https://www.ncbi.nlm.nih.gov/pubmed/37095855
http://dx.doi.org/10.1089/neur.2022.0087
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author Andreu, MaryLourdes
Sanchez, Liz M. Quesada
Spurlock, Markus S.
Hu, Zhen
Mahavadi, Anil
Powell, Henry R.
Lujan, Maria M.
Nodal, Samuel
Cera, Melissa
Ciocca, Isabella
Bullock, Ross
Gajavelli, Shyam
author_facet Andreu, MaryLourdes
Sanchez, Liz M. Quesada
Spurlock, Markus S.
Hu, Zhen
Mahavadi, Anil
Powell, Henry R.
Lujan, Maria M.
Nodal, Samuel
Cera, Melissa
Ciocca, Isabella
Bullock, Ross
Gajavelli, Shyam
author_sort Andreu, MaryLourdes
collection PubMed
description Penetrating traumatic brain injury (pTBI) is increasingly survivable, but permanently disabling as adult mammalian nervous system does not regenerate. Recently, our group demonstrated transplant location-dependent neuroprotection and safety of clinical trial–grade human neural stem cell (hNSC) transplantation in a rodent model of acute pTBI. To evaluate whether longer injury-transplantation intervals marked by chronic inflammation impede engraftment, 60 male Sprague-Dawley rats were randomized to three sets. Each set was divided equally into two groups: 1) with no injury (sham) or 2) pTBI. After either 1 week (groups 1 and 2), 2 weeks (groups 3 and 4), or 4 weeks after injury (groups 5 and 6), each animal received 0.5 million hNSCs perilesionally. A seventh group of pTBI animals treated with vehicle served as the negative control. All animals were allowed to survive 12 weeks with standard chemical immunosuppression. Motor capacity was assessed pre-transplant to establish injury-induced deficit and followed by testing at 8 and 12 weeks after transplantation. Animals were euthanized, perfused, and examined for lesion size, axonal degeneration, and engraftment. Compared to vehicle, transplanted groups showed a trend for reduced lesion size and axonal injury across intervals. Remote secondary axonal injury was significantly reduced in groups 2 and 4, but not in group 6. The majority of animals showed robust engraftment independent of the injury-transplant time interval. Modest amelioration of motor deficit paralleled the axonal injury trend. In aggregate, pTBI-induced remote secondary axonal injury was resolved by early, but not delayed, hNSC transplantation.
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spelling pubmed-101222352023-04-23 Injury-Transplantation Interval-Dependent Amelioration of Axonal Degeneration and Motor Deficit in Rats with Penetrating Traumatic Brain Injury Andreu, MaryLourdes Sanchez, Liz M. Quesada Spurlock, Markus S. Hu, Zhen Mahavadi, Anil Powell, Henry R. Lujan, Maria M. Nodal, Samuel Cera, Melissa Ciocca, Isabella Bullock, Ross Gajavelli, Shyam Neurotrauma Rep Original Article Penetrating traumatic brain injury (pTBI) is increasingly survivable, but permanently disabling as adult mammalian nervous system does not regenerate. Recently, our group demonstrated transplant location-dependent neuroprotection and safety of clinical trial–grade human neural stem cell (hNSC) transplantation in a rodent model of acute pTBI. To evaluate whether longer injury-transplantation intervals marked by chronic inflammation impede engraftment, 60 male Sprague-Dawley rats were randomized to three sets. Each set was divided equally into two groups: 1) with no injury (sham) or 2) pTBI. After either 1 week (groups 1 and 2), 2 weeks (groups 3 and 4), or 4 weeks after injury (groups 5 and 6), each animal received 0.5 million hNSCs perilesionally. A seventh group of pTBI animals treated with vehicle served as the negative control. All animals were allowed to survive 12 weeks with standard chemical immunosuppression. Motor capacity was assessed pre-transplant to establish injury-induced deficit and followed by testing at 8 and 12 weeks after transplantation. Animals were euthanized, perfused, and examined for lesion size, axonal degeneration, and engraftment. Compared to vehicle, transplanted groups showed a trend for reduced lesion size and axonal injury across intervals. Remote secondary axonal injury was significantly reduced in groups 2 and 4, but not in group 6. The majority of animals showed robust engraftment independent of the injury-transplant time interval. Modest amelioration of motor deficit paralleled the axonal injury trend. In aggregate, pTBI-induced remote secondary axonal injury was resolved by early, but not delayed, hNSC transplantation. Mary Ann Liebert, Inc., publishers 2023-04-10 /pmc/articles/PMC10122235/ /pubmed/37095855 http://dx.doi.org/10.1089/neur.2022.0087 Text en © MaryLourdes Andreu et al., 2023; Published by Mary Ann Liebert, Inc. https://creativecommons.org/licenses/by/4.0/This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Andreu, MaryLourdes
Sanchez, Liz M. Quesada
Spurlock, Markus S.
Hu, Zhen
Mahavadi, Anil
Powell, Henry R.
Lujan, Maria M.
Nodal, Samuel
Cera, Melissa
Ciocca, Isabella
Bullock, Ross
Gajavelli, Shyam
Injury-Transplantation Interval-Dependent Amelioration of Axonal Degeneration and Motor Deficit in Rats with Penetrating Traumatic Brain Injury
title Injury-Transplantation Interval-Dependent Amelioration of Axonal Degeneration and Motor Deficit in Rats with Penetrating Traumatic Brain Injury
title_full Injury-Transplantation Interval-Dependent Amelioration of Axonal Degeneration and Motor Deficit in Rats with Penetrating Traumatic Brain Injury
title_fullStr Injury-Transplantation Interval-Dependent Amelioration of Axonal Degeneration and Motor Deficit in Rats with Penetrating Traumatic Brain Injury
title_full_unstemmed Injury-Transplantation Interval-Dependent Amelioration of Axonal Degeneration and Motor Deficit in Rats with Penetrating Traumatic Brain Injury
title_short Injury-Transplantation Interval-Dependent Amelioration of Axonal Degeneration and Motor Deficit in Rats with Penetrating Traumatic Brain Injury
title_sort injury-transplantation interval-dependent amelioration of axonal degeneration and motor deficit in rats with penetrating traumatic brain injury
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122235/
https://www.ncbi.nlm.nih.gov/pubmed/37095855
http://dx.doi.org/10.1089/neur.2022.0087
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