PMID- 30682785
OWN - NLM
STAT- MEDLINE
DCOM- 20190508
LR  - 20201224
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 3
DP  - 2019 Jan 24
TI  - Post-Injury Neuroprotective Effects of the Thalidomide Analog 
      3,6'-Dithiothalidomide on Traumatic Brain Injury.
LID - 10.3390/ijms20030502 [doi]
LID - 502
AB  - 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-alpha (TNF-alpha) 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-alpha 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.
FAU - Batsaikhan, Buyandelger
AU  - Batsaikhan B
AD  - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical 
      University, 250 Wu-Xing Street, Taipei 11031, Taiwan. buyndlgr@gmail.com.
FAU - Wang, Jing-Ya
AU  - Wang JY
AD  - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical 
      University, 250 Wu-Xing Street, Taipei 11031, Taiwan. 
      gaeajyw911real@hotmail.com.tw.
FAU - Scerba, Michael T
AU  - Scerba MT
AD  - Drug Design & Development Section, Translational Gerontology Branch, Intramural 
      Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA. 
      mike.scerba@nih.gov.
FAU - Tweedie, David
AU  - Tweedie D
AD  - Drug Design & Development Section, Translational Gerontology Branch, Intramural 
      Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA. 
      tweedieda@grc.nia.nih.gov.
FAU - Greig, Nigel H
AU  - Greig NH
AD  - Drug Design & Development Section, Translational Gerontology Branch, Intramural 
      Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA. 
      greign@grc.nia.nih.gov.
FAU - Miller, Jonathan P
AU  - Miller JP
AD  - Department of Neurological Surgery, Case Western Reserve University, Cleveland, 
      OH 44106, USA. Jonathan.Miller@uhhospitals.org.
FAU - Hoffer, Barry J
AU  - Hoffer BJ
AD  - Department of Neurological Surgery, Case Western Reserve University, Cleveland, 
      OH 44106, USA. bjh82@case.edu.
FAU - Lin, Chih-Tung
AU  - Lin CT
AUID- ORCID: 0000-0002-1482-513X
AD  - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical 
      University, 250 Wu-Xing Street, Taipei 11031, Taiwan. sss880205@gmail.com.
FAU - Wang, Jia-Yi
AU  - Wang JY
AD  - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical 
      University, 250 Wu-Xing Street, Taipei 11031, Taiwan. jywang2010@tmu.edu.tw.
AD  - Department of Physiology, School of Medicine, College of Medicine, Taipei Medical 
      University, Taipei 11031, Taiwan. jywang2010@tmu.edu.tw.
LA  - eng
GR  - R56 AG057028/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20190124
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (3,6'-dithiothalidomide)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 4Z8R6ORS6L (Thalidomide)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology/*therapeutic use
MH  - Brain Injuries, Traumatic/*drug therapy
MH  - Cell Line
MH  - Male
MH  - Mice
MH  - Neurons/drug effects/metabolism
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thalidomide/*analogs & derivatives/pharmacology/therapeutic use
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC6387371
OTO - NOTNLM
OT  - 3,6'-dithiothalidomide
OT  - neurodegeneration
OT  - neuroinflammation
OT  - neurological deficits
OT  - oxidative stress
OT  - traumatic brain injury
COIS- The authors declare no conflict of interest.
EDAT- 2019/01/27 06:00
MHDA- 2019/05/09 06:00
PMCR- 2019/02/01
CRDT- 2019/01/27 06:00
PHST- 2018/12/28 00:00 [received]
PHST- 2019/01/18 00:00 [revised]
PHST- 2019/01/21 00:00 [accepted]
PHST- 2019/01/27 06:00 [entrez]
PHST- 2019/01/27 06:00 [pubmed]
PHST- 2019/05/09 06:00 [medline]
PHST- 2019/02/01 00:00 [pmc-release]
AID - ijms20030502 [pii]
AID - ijms-20-00502 [pii]
AID - 10.3390/ijms20030502 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Jan 24;20(3):502. doi: 10.3390/ijms20030502.