Format

Send to

Choose Destination
Int J Mol Sci. 2019 Jan 24;20(3). pii: E502. doi: 10.3390/ijms20030502.

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

Author information

1
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Xing Street, Taipei 11031, Taiwan. buyndlgr@gmail.com.
2
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Xing Street, Taipei 11031, Taiwan. gaeajyw911real@hotmail.com.tw.
3
Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA. mike.scerba@nih.gov.
4
Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA. tweedieda@grc.nia.nih.gov.
5
Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA. greign@grc.nia.nih.gov.
6
Department of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. Jonathan.Miller@uhhospitals.org.
7
Department of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. bjh82@case.edu.
8
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Xing Street, Taipei 11031, Taiwan. sss880205@gmail.com.
9
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Xing Street, Taipei 11031, Taiwan. jywang2010@tmu.edu.tw.
10
Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. jywang2010@tmu.edu.tw.

Abstract

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.

KEYWORDS:

3,6′-dithiothalidomide; neurodegeneration; neuroinflammation; neurological deficits; oxidative stress; traumatic brain injury

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center