PMID- 16267216
OWN - NLM
STAT- MEDLINE
DCOM- 20060313
LR  - 20211025
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 25
IP  - 44
DP  - 2005 Nov 2
TI  - Tumor necrosis factor-like weak inducer of apoptosis increases the permeability 
      of the neurovascular unit through nuclear factor-kappa B pathway activation.
PG  - 10094-100
AB  - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the 
      tumor necrosis factor superfamily. TWEAK acts on responsive cells via binding to 
      a small cell-surface receptor named fibroblast growth factor-inducible-14 (Fn14). 
      TWEAK can stimulate numerous cellular responses including cell proliferation, 
      migration, and proinflammatory molecule production. The present study 
      investigated whether TWEAK plays a role in the regulation of the permeability of 
      the neurovascular unit (NVU). We found that intracerebral injection of TWEAK in 
      wild-type mice induces activation of the nuclear factor-kappaB (NF-kappaB) 
      pathway and matrix metalloproteinase-9 (MMP-9) expression in the brain with 
      resultant disruption in the structure of the NVU and increase in the permeability 
      of the blood-brain barrier (BBB). TWEAK did not increase MMP-9 activity or BBB 
      permeability when injected into mice genetically deficient in the NF-kappaB 
      family member p50. Furthermore, we report that inhibition of TWEAK activity 
      during cerebral ischemia with an Fn14-Fc decoy receptor results in significant 
      preservation of the integrity of the NVU with attenuation of cerebral 
      ischemia-induced increase in the permeability of the BBB. We conclude that the 
      cytokine TWEAK plays a role in the disruption of the structure and permeability 
      of the NVU during physiological and pathological conditions.
FAU - Polavarapu, Rohini
AU  - Polavarapu R
AD  - Department of Neurology, Center for Neurodegenerative Disease, Emory University 
      School of Medicine, Atlanta, Georgia 30322, USA.
FAU - Gongora, Maria Carolina
AU  - Gongora MC
FAU - Winkles, Jeffrey A
AU  - Winkles JA
FAU - Yepes, Manuel
AU  - Yepes M
LA  - eng
GR  - R01 HL039727/HL/NHLBI NIH HHS/United States
GR  - R01 NS049478/NS/NINDS NIH HHS/United States
GR  - HL-39727/HL/NHLBI NIH HHS/United States
GR  - NS-49478/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Cytokine TWEAK)
RN  - 0 (NF-kappa B)
RN  - 0 (Tnfsf12 protein, mouse)
RN  - 0 (Tumor Necrosis Factors)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Blood-Brain Barrier/physiology
MH  - Capillary Permeability/*physiology
MH  - Cytokine TWEAK
MH  - Endothelium, Vascular/metabolism/*physiology
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-kappa B/*metabolism/physiology
MH  - Neurons/*metabolism
MH  - Signal Transduction/*physiology
MH  - Tumor Necrosis Factors/*physiology
PMC - PMC6725778
EDAT- 2005/11/04 09:00
MHDA- 2006/03/15 09:00
PMCR- 2006/05/02
CRDT- 2005/11/04 09:00
PHST- 2005/11/04 09:00 [pubmed]
PHST- 2006/03/15 09:00 [medline]
PHST- 2005/11/04 09:00 [entrez]
PHST- 2006/05/02 00:00 [pmc-release]
AID - 25/44/10094 [pii]
AID - 10.1523/JNEUROSCI.3382-05.2005 [doi]
PST - ppublish
SO  - J Neurosci. 2005 Nov 2;25(44):10094-100. doi: 10.1523/JNEUROSCI.3382-05.2005.