PMID- 24236179
OWN - NLM
STAT- MEDLINE
DCOM- 20140725
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - Endothelial nitric oxide synthase regulates white matter changes via the 
      BDNF/TrkB pathway after stroke in mice.
PG  - e80358
LID - 10.1371/journal.pone.0080358 [doi]
LID - e80358
AB  - Stroke induced white matter (WM) damage is associated with neurological 
      functional deficits, but the underlying mechanisms are not well understood. In 
      this study, we investigate whether endothelial nitric oxide synthase (eNOS) 
      affects WM-damage post-stroke. Adult male wild-type (WT) and eNOS knockout 
      (eNOS(-/-)) mice were subjected to middle cerebral artery occlusion. Functional 
      evaluation, infarct volume measurement, immunostaining and primary cortical cell 
      culture were performed. To obtain insight into the mechanisms underlying the 
      effects of eNOS(-/-) on WM-damage, measurement of eNOS, brain-derived 
      neurotrophic factor (BDNF) and its receptor TrkB in vivo and in vitro were also 
      performed. No significant differences were detected in the infarction volume, 
      myelin density in the ipsilateral striatal WM-bundles and myelin-based protein 
      expression in the cerebral ischemic border between WT and eNOS(-/-) mice. 
      However, eNOS(-/-) mice showed significantly: 1) decreased functional outcome, 
      concurrent with decreases of total axon density and phosphorylated high-molecular 
      weight neurofilament density in the ipsilateral striatal WM-bundles. Correlation 
      analysis showed that axon density is significantly positive correlated with 
      neurological functional outcome; 2) decreased numbers of oligodendrocytes / 
      oligodendrocyte progenitor cells in the ipsilateral striatum; 3) decreased 
      synaptophysin, BDNF and TrkB expression in the ischemic border compared with WT 
      mice after stroke (n = 12/group, p<0.05). Primary cortical cell culture confirmed 
      that the decrease of neuronal neurite outgrowth in the neurons derived from 
      eNOS(-/-) mice is mediated by the reduction of BDNF/TrkB (n = 6/group, p<0.05). 
      Our data show that eNOS plays a critical role in WM-damage after stroke, and 
      eNOS(-/-)-induced decreases in the BDNF/TrkB pathway may contribute to increased 
      WM-damage, and thereby decrease functional outcome.
FAU - Cui, Xu
AU  - Cui X
AD  - Department of Neurology, Henry Ford Hospital, Detroit, Michigan, United States of 
      America.
FAU - Chopp, Michael
AU  - Chopp M
FAU - Zacharek, Alex
AU  - Zacharek A
FAU - Ning, Ruizhuo
AU  - Ning R
FAU - Ding, Xiaoshuang
AU  - Ding X
FAU - Roberts, Cynthia
AU  - Roberts C
FAU - Chen, Jieli
AU  - Chen J
LA  - eng
GR  - R01 AG031811/AG/NIA NIH HHS/United States
GR  - R01 AG037506/AG/NIA NIH HHS/United States
GR  - R41 NS064708/NS/NINDS NIH HHS/United States
GR  - 1R41NS064708/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131113
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain/metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Disease Models, Animal
MH  - Infarction, Middle Cerebral Artery
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Myelin Sheath/*metabolism/*pathology
MH  - Neurites/metabolism
MH  - Nitric Oxide Synthase Type III/*metabolism
MH  - Oligodendroglia/metabolism
MH  - Receptor, trkB/*metabolism
MH  - *Signal Transduction
MH  - Stroke/*metabolism/mortality
MH  - Synapses/metabolism
PMC - PMC3827451
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/16 06:00
MHDA- 2014/07/26 06:00
PMCR- 2013/11/13
CRDT- 2013/11/16 06:00
PHST- 2013/08/29 00:00 [received]
PHST- 2013/10/02 00:00 [accepted]
PHST- 2013/11/16 06:00 [entrez]
PHST- 2013/11/16 06:00 [pubmed]
PHST- 2014/07/26 06:00 [medline]
PHST- 2013/11/13 00:00 [pmc-release]
AID - PONE-D-13-35623 [pii]
AID - 10.1371/journal.pone.0080358 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 13;8(11):e80358. doi: 10.1371/journal.pone.0080358. 
      eCollection 2013.