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Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Long-term deficits after TBI arise not only from the direct effects of the injury but also from ongoing processes such as neuronal excitotoxicity, inflammation, oxidative stress and apoptosis. Tumor necrosis factor-...

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Autores principales: Batsaikhan, Buyandelger, Wang, Jing-Ya, Scerba, Michael T., Tweedie, David, Greig, Nigel H., Miller, Jonathan P., Hoffer, Barry J., Lin, Chih-Tung, Wang, Jia-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387371/
https://www.ncbi.nlm.nih.gov/pubmed/30682785
http://dx.doi.org/10.3390/ijms20030502
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author Batsaikhan, Buyandelger
Wang, Jing-Ya
Scerba, Michael T.
Tweedie, David
Greig, Nigel H.
Miller, Jonathan P.
Hoffer, Barry J.
Lin, Chih-Tung
Wang, Jia-Yi
author_facet Batsaikhan, Buyandelger
Wang, Jing-Ya
Scerba, Michael T.
Tweedie, David
Greig, Nigel H.
Miller, Jonathan P.
Hoffer, Barry J.
Lin, Chih-Tung
Wang, Jia-Yi
author_sort Batsaikhan, Buyandelger
collection PubMed
description Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Long-term deficits after TBI arise not only from the direct effects of the injury but also from ongoing processes such as neuronal excitotoxicity, inflammation, oxidative stress and apoptosis. Tumor necrosis factor-α (TNF-α) is known to contribute to these processes. We have previously shown that 3,6′-dithiothalidomide (3,6′-DT), a thalidomide analog that is more potent than thalidomide with similar brain penetration, selectively inhibits the synthesis of TNF-α in cultured cells and reverses behavioral impairments induced by mild TBI in mice. In the present study, we further explored the therapeutic potential of 3,6′-DT in an animal model of moderate TBI using Sprague-Dawley rats subjected to controlled cortical impact. A single dose of 3,6′-DT (28 mg/kg, i.p.) at 5 h after TBI significantly reduced contusion volume, neuronal degeneration, neuronal apoptosis and neurological deficits at 24 h post-injury. Expression of pro-inflammatory cytokines in the contusion regions were also suppressed at the transcription and translation level by 3,6′-DT. Notably, neuronal oxidative stress was also suppressed by 3,6′-DT. We conclude that 3,6′-DT may represent a potential therapy to ameliorate TBI-induced functional deficits.
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spelling pubmed-63873712019-02-27 Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury Batsaikhan, Buyandelger Wang, Jing-Ya Scerba, Michael T. Tweedie, David Greig, Nigel H. Miller, Jonathan P. Hoffer, Barry J. Lin, Chih-Tung Wang, Jia-Yi Int J Mol Sci Article Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Long-term deficits after TBI arise not only from the direct effects of the injury but also from ongoing processes such as neuronal excitotoxicity, inflammation, oxidative stress and apoptosis. Tumor necrosis factor-α (TNF-α) is known to contribute to these processes. We have previously shown that 3,6′-dithiothalidomide (3,6′-DT), a thalidomide analog that is more potent than thalidomide with similar brain penetration, selectively inhibits the synthesis of TNF-α in cultured cells and reverses behavioral impairments induced by mild TBI in mice. In the present study, we further explored the therapeutic potential of 3,6′-DT in an animal model of moderate TBI using Sprague-Dawley rats subjected to controlled cortical impact. A single dose of 3,6′-DT (28 mg/kg, i.p.) at 5 h after TBI significantly reduced contusion volume, neuronal degeneration, neuronal apoptosis and neurological deficits at 24 h post-injury. Expression of pro-inflammatory cytokines in the contusion regions were also suppressed at the transcription and translation level by 3,6′-DT. Notably, neuronal oxidative stress was also suppressed by 3,6′-DT. We conclude that 3,6′-DT may represent a potential therapy to ameliorate TBI-induced functional deficits. MDPI 2019-01-24 /pmc/articles/PMC6387371/ /pubmed/30682785 http://dx.doi.org/10.3390/ijms20030502 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Batsaikhan, Buyandelger
Wang, Jing-Ya
Scerba, Michael T.
Tweedie, David
Greig, Nigel H.
Miller, Jonathan P.
Hoffer, Barry J.
Lin, Chih-Tung
Wang, Jia-Yi
Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury
title Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury
title_full Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury
title_fullStr Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury
title_full_unstemmed Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury
title_short Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury
title_sort post-injury neuroprotective effects of the thalidomide analog 3,6′-dithiothalidomide on traumatic brain injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387371/
https://www.ncbi.nlm.nih.gov/pubmed/30682785
http://dx.doi.org/10.3390/ijms20030502
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