Post-injury neuroprotective effects of the thalidomide analog 3,6′-dithiothalidomide on traumatic brain injury

Buyandelger Batsaikhan, Jing Ya Wang, Michael T. Scerba, David Tweedie, Nigel H. Greig, Jonathan P. Miller, Barry J. Hoffer, Chih Tung Lin, Jia Yi Wang

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Article number502
JournalInternational Journal of Molecular Sciences
Volume20
Issue number3
DOIs
Publication statusPublished - Feb 1 2019

Keywords

  • 3,6′-dithiothalidomide
  • Neurodegeneration
  • Neuroinflammation
  • Neurological deficits
  • Oxidative stress
  • Traumatic brain injury

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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