PMID- 31914858
OWN - NLM
STAT- MEDLINE
DCOM- 20211007
LR  - 20211007
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Linking)
VI  - 37
IP  - 10
DP  - 2020 May 15
TI  - Curcumin Protects against White Matter Injury through NF-kappaB and Nrf2 Cross Talk.
PG  - 1255-1265
LID - 10.1089/neu.2019.6749 [doi]
AB  - Inflammation and oxidative stress play a central role in the pathogenesis of 
      white matter injury (WMI). Curcumin (Cur), a polyphenolic compound, exhibits 
      anti-inflammatory and anti-oxidant effects on several conditions. The objective 
      of this study was to investigate neuroprotective effects of Cur on WMI and 
      explore its underlying mechanisms of action. Sprague-Dawley rats were subjected 
      to the removal of white matter from the dorsal column of the spinal cord. Dorsal 
      columns were randomly divided into three groups: Sham (Ringer's solution bubbled 
      with 95% O(2) and 5% CO(2)), hypoxia (Hyp; Ringer's solution bubbled with 95% 
      N(2) and 5% CO(2) for 1 h), and Cur-treated (Hyp+Cur; Ringer's solution bubbled 
      with 95% N(2) and 5% CO(2) for 1 h in the presence of 50 muM Cur). For NF-kappaB 
      inhibition experiments, dorsal columns were incubated with 50 muM BAY 11-7082 
      (BAY) for 30 min in 95% O(2) and 5% CO(2) prior to 1-h incubation with 50 muM Cur 
      in 95% N(2) and 5% CO(2). Our data show that Cur inhibited hypoxia-induced HIF1-alpha 
      expression and tissue damage by demonstrating the improved morphology of 
      astrocytes and remarkable reduction in vacuolation. Cur also inhibited the 
      hypoxia-induced upregulation of glial fibrillary acidic protein (GFAP) and 
      neurofilament-H (NF-H) after hypoxia and downregulated the expression of 
      pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and 
      interleukin 1 (IL-1). Terminal dexynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL)-assay analysis showed that Cur effectively attenuated apoptosis 
      in white matter. In addition, we demonstrated that Cur exerted its 
      neuroprotective effect through cross talk between nuclear factor 
      kappa-light-chain-enhancer of activated B (NF-kappaB) and nuclear factor erythroid 
      2-related factor 2 (Nrf2) signaling pathways. In conclusion, our results indicate 
      that treatment with Cur inhibited the hypoxia, inflammation and apoptosis 
      associated with WMI. Further, the Nrf-2 pathway inhibits NF-kappaB activation by 
      preventing IkB degradation and increasing HO-1 expression, which in turn reduces 
      reactive oxygen species (ROS) and as a result NF-kappaB activation is suppressed. 
      Similarly, NF-kappaB-mediated transcription reduces Nrf2 activation by reducing 
      anti-oxidant response element (ARE) gene and free CREB binding protein by 
      competing with Nrf2 for CBP thus inhibiting the Nrf-2 activation.
FAU - Daverey, Amita
AU  - Daverey A
AD  - Department of Neurosurgery, University of Nebraska Medical Center, Omaha, 
      Nebraska, USA.
FAU - Agrawal, Sandeep K
AU  - Agrawal SK
AD  - Department of Neurosurgery, University of Nebraska Medical Center, Omaha, 
      Nebraska, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200205
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nfe2l2 protein, rat)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Cell Hypoxia/drug effects/physiology
MH  - Curcumin/*pharmacology
MH  - Male
MH  - NF-E2-Related Factor 2/*metabolism
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Neuroprotective Agents/pharmacology
MH  - Organ Culture Techniques
MH  - Oxidative Stress/drug effects/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Spinal Cord/drug effects/metabolism
MH  - White Matter/*drug effects/injuries/*metabolism
OTO - NOTNLM
OT  - curcumin
OT  - hypoxia
OT  - oxidative stress
OT  - polyphenolic compounds
OT  - spinal cord injury
OT  - white matter
EDAT- 2020/01/10 06:00
MHDA- 2021/10/08 06:00
CRDT- 2020/01/10 06:00
PHST- 2020/01/10 06:00 [pubmed]
PHST- 2021/10/08 06:00 [medline]
PHST- 2020/01/10 06:00 [entrez]
AID - 10.1089/neu.2019.6749 [doi]
PST - ppublish
SO  - J Neurotrauma. 2020 May 15;37(10):1255-1265. doi: 10.1089/neu.2019.6749. Epub 
      2020 Feb 5.