PMID- 34073455
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210710
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 10
IP  - 6
DP  - 2021 May 26
TI  - TNF-alpha Receptor Inhibitor Alleviates Metabolic and Inflammatory Changes in a Rat 
      Model of Ischemic Stroke.
LID - 10.3390/antiox10060851 [doi]
LID - 851
AB  - Hyperglycemia and inflammation, with their augmented interplay, are involved in 
      cases of stroke with poor outcomes. Interrupting this vicious cycle thus has the 
      potential to prevent stroke disease progression. Tumor necrosis factor-alpha (TNF-alpha) 
      is an emerging molecule, which has inflammatory and metabolic roles. Studies have 
      shown that TNF-alpha receptor inhibitor R-7050 possesses neuroprotective, 
      antihyperglycemic, and anti-inflammatory effects. Using a rat model of permanent 
      cerebral ischemia, pretreatment with R-7050 offered protection against poststroke 
      neurological deficits, brain infarction, edema, oxidative stress, and caspase 3 
      activation. In the injured cortical tissues, R-7050 reversed the activation of 
      TNF receptor-I (TNFRI), NF-kappaB, and interleukin-6 (IL-6), as well as the reduction 
      of zonula occludens-1 (ZO-1). In the in vitro study on bEnd.3 endothelial cells, 
      R-7050 reduced the decline of ZO-1 levels after TNF-alpha-exposure. R-7050 also 
      reduced the metabolic alterations occurring after ischemic stroke, such as 
      hyperglycemia and increased plasma corticosterone, free fatty acids, C reactive 
      protein, and fibroblast growth factor-15 concentrations. In the gastrocnemius 
      muscles of rats with stroke, R-7050 improved activated TNFRI/NF-kappaB, oxidative 
      stress, and IL-6 pathways, as well as impaired insulin signaling. Overall, our 
      findings highlight a feasible way to combat stroke disease based on an anti-TNF 
      therapy that involves anti-inflammatory and metabolic mechanisms.
FAU - Lin, Shih-Yi
AU  - Lin SY
AUID- ORCID: 0000-0002-1901-2656
AD  - Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, 
      Taichung City 407, Taiwan.
AD  - Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 
      City 112, Taiwan.
FAU - Wang, Ya-Yu
AU  - Wang YY
AD  - Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 
      City 112, Taiwan.
AD  - Department of Family Medicine, Taichung Veterans General Hospital, Taichung City 
      407, Taiwan.
FAU - Chang, Cheng-Yi
AU  - Chang CY
AD  - Department of Surgery, Feng Yuan Hospital, Taichung City 420, Taiwan.
FAU - Wu, Chih-Cheng
AU  - Wu CC
AD  - Department of Anesthesiology, Taichung Veterans General Hospital, Taichung City 
      407, Taiwan.
AD  - Department of Financial Engineering, Providence University, Taichung City 433, 
      Taiwan.
AD  - Department of Data Science and Big Data Analytics, Providence University, 
      Taichung City 433, Taiwan.
FAU - Chen, Wen-Ying
AU  - Chen WY
AUID- ORCID: 0000-0002-5105-5285
AD  - Department of Veterinary Medicine, National Chung-Hsing University, Taichung City 
      402, Taiwan.
FAU - Liao, Su-Lan
AU  - Liao SL
AD  - Department of Medical Research, Taichung Veterans General Hospital, Taichung City 
      407, Taiwan.
FAU - Chen, Chun-Jung
AU  - Chen CJ
AD  - Department of Medical Research, Taichung Veterans General Hospital, Taichung City 
      407, Taiwan.
AD  - Department of Medical Laboratory Science and Biotechnology, China Medical 
      University, Taichung City 404, Taiwan.
LA  - eng
GR  - MOST 105-2314-B-075A-004-MY3/Ministry of Science and Technology, Taiwan/
GR  - MOST 105-2314-B-075A-006-MY3/Ministry of Science and Technology, Taiwan/
GR  - TCVGH-1108201C/Taichung Veterans General Hospital, Taiwan/
PT  - Journal Article
DEP - 20210526
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC8228519
OTO - NOTNLM
OT  - TNF-alpha
OT  - hyperglycemia
OT  - insulin resistance
OT  - neuroinflammation
OT  - stroke
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2021/06/03 06:00
MHDA- 2021/06/03 06:01
PMCR- 2021/05/26
CRDT- 2021/06/02 01:38
PHST- 2021/04/21 00:00 [received]
PHST- 2021/05/14 00:00 [revised]
PHST- 2021/05/24 00:00 [accepted]
PHST- 2021/06/02 01:38 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/06/03 06:01 [medline]
PHST- 2021/05/26 00:00 [pmc-release]
AID - antiox10060851 [pii]
AID - antioxidants-10-00851 [pii]
AID - 10.3390/antiox10060851 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2021 May 26;10(6):851. doi: 10.3390/antiox10060851.