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GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury

The reparative process following spinal cord injury (SCI) is extremely complicated. Cells in the microenvironment express multiple inhibitory factors that affect axonal regeneration over a prolonged period of time. The axon growth inhibitory factor glycogen synthase kinase-3 (GSK-3) is an important...

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Autores principales: Lei, Fei, He, Wen, Tian, Xinggui, Zhou, Qingzhong, Zheng, Lipeng, Kang, Jianping, Song, Yueming, Feng, Daxiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699364/
https://www.ncbi.nlm.nih.gov/pubmed/31467921
http://dx.doi.org/10.1155/2019/9628065
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author Lei, Fei
He, Wen
Tian, Xinggui
Zhou, Qingzhong
Zheng, Lipeng
Kang, Jianping
Song, Yueming
Feng, Daxiong
author_facet Lei, Fei
He, Wen
Tian, Xinggui
Zhou, Qingzhong
Zheng, Lipeng
Kang, Jianping
Song, Yueming
Feng, Daxiong
author_sort Lei, Fei
collection PubMed
description The reparative process following spinal cord injury (SCI) is extremely complicated. Cells in the microenvironment express multiple inhibitory factors that affect axonal regeneration over a prolonged period of time. The axon growth inhibitory factor glycogen synthase kinase-3 (GSK-3) is an important factor during these processes. TDZD-8 (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione) is the most effective and specific non-ATP-competitive inhibitor of GSK-3. Here, we show that administering TDZD-8 after SCI was associated with significantly inhibited neuronal apoptosis, upregulated GAP-43 expression, increased density of cortical spinal tract fibers around areas of injury, and increased Basso, Beattie, and Bresnahan (BBB) scores in the lower limbs. These findings support the notion that GSK-3 inhibitors promote neuronal cell regeneration and lower limb functional recovery.
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spelling pubmed-66993642019-08-29 GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury Lei, Fei He, Wen Tian, Xinggui Zhou, Qingzhong Zheng, Lipeng Kang, Jianping Song, Yueming Feng, Daxiong Biomed Res Int Research Article The reparative process following spinal cord injury (SCI) is extremely complicated. Cells in the microenvironment express multiple inhibitory factors that affect axonal regeneration over a prolonged period of time. The axon growth inhibitory factor glycogen synthase kinase-3 (GSK-3) is an important factor during these processes. TDZD-8 (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione) is the most effective and specific non-ATP-competitive inhibitor of GSK-3. Here, we show that administering TDZD-8 after SCI was associated with significantly inhibited neuronal apoptosis, upregulated GAP-43 expression, increased density of cortical spinal tract fibers around areas of injury, and increased Basso, Beattie, and Bresnahan (BBB) scores in the lower limbs. These findings support the notion that GSK-3 inhibitors promote neuronal cell regeneration and lower limb functional recovery. Hindawi 2019-08-04 /pmc/articles/PMC6699364/ /pubmed/31467921 http://dx.doi.org/10.1155/2019/9628065 Text en Copyright © 2019 Fei Lei et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lei, Fei
He, Wen
Tian, Xinggui
Zhou, Qingzhong
Zheng, Lipeng
Kang, Jianping
Song, Yueming
Feng, Daxiong
GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury
title GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury
title_full GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury
title_fullStr GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury
title_full_unstemmed GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury
title_short GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury
title_sort gsk-3 inhibitor promotes neuronal cell regeneration and functional recovery in a rat model of spinal cord injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699364/
https://www.ncbi.nlm.nih.gov/pubmed/31467921
http://dx.doi.org/10.1155/2019/9628065
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