PMID- 24397751
OWN - NLM
STAT- MEDLINE
DCOM- 20140908
LR  - 20220331
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 20
IP  - 2
DP  - 2014 Feb
TI  - Endothelial nitric oxide synthase protects neurons against ischemic injury 
      through regulation of brain-derived neurotrophic factor expression.
PG  - 154-64
LID - 10.1111/cns.12182 [doi]
AB  - AIMS: Several lines of evidence demonstrated that endothelial nitric oxide 
      synthase (eNOS) confers protective effects during cerebral ischemia. In this 
      study, we explored the underlying cellular and molecular mechanisms of 
      neuroprotection by eNOS. METHODS: A series of in vivo and in vitro ischemic 
      models were employed to study the role of eNOS in maintaining neuronal survival 
      and to identify the downstream factors. RESULTS: The current data showed that 
      pretreatment with a specific eNOS inhibitor, L-N5-(1-iminoethyl) ornithine 
      (L-NIO), aggravated the neuronal loss in the rat cerebral ischemic model, 
      accompanied by reduction in brain-derived neurotrophic factor (BDNF) level, which 
      was consistent with the findings in an oxygen-glucose deprivation model (OGD) 
      with two neuronal cells: primary rat cortical neurons and human neuroblastoma 
      SH-SY5Y cells. Furthermore, the extensive neuronal loss induced by L-NIO was 
      totally abolished by exogenous BDNF in both in vitro and in vivo models. On the 
      other hand, eNOS overexpression through an adenoviral vector exerted a prominent 
      protective effect on the neuronal cells subject to OGD, and the protective effect 
      was totally abrogated by a neutralizing anti-BDNF antibody. CONCLUSION: 
      Collectively, our results indicate that the neuroprotection of neuron-derived 
      eNOS against the cerebral ischemia was mediated through the regulation of BDNF 
      secretion. In conclusion, our discovery provides a novel explanation for the 
      neuroprotective effect of eNOS under pathological ischemic conditions such as 
      stroke.
CI  - (c) 2014 John Wiley & Sons Ltd.
FAU - Li, Shi-Ting
AU  - Li ST
AD  - Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University School 
      of Medicine, Shanghai, China.
FAU - Pan, Jing
AU  - Pan J
FAU - Hua, Xu-Ming
AU  - Hua XM
FAU - Liu, Hong
AU  - Liu H
FAU - Shen, Sa
AU  - Shen S
FAU - Liu, Jia-Fu
AU  - Liu JF
FAU - Li, Bin
AU  - Li B
FAU - Tao, Bang-Bao
AU  - Tao BB
FAU - Ge, Xiao-Li
AU  - Ge XL
FAU - Wang, Xu-Hui
AU  - Wang XH
FAU - Shi, Juan-Hong
AU  - Shi JH
FAU - Wang, Xiao-Qiang
AU  - Wang XQ
LA  - eng
PT  - Journal Article
DEP - 20140108
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Antibodies)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 36889-13-1 (N(G)-iminoethylornithine)
RN  - E524N2IXA3 (Ornithine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 3.4.22.- (Caspase 3)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology/therapeutic use
MH  - Brain/drug effects/*pathology
MH  - Brain-Derived Neurotrophic Factor/immunology/*metabolism
MH  - Caspase 3/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Glucose/deficiency
MH  - Humans
MH  - Hypoxia/pathology/prevention & control
MH  - Ischemic Attack, Transient/*pathology/*prevention & control
MH  - Male
MH  - Neurons/drug effects/*physiology
MH  - Nitric Oxide Synthase Type III/immunology/*metabolism
MH  - Ornithine/analogs & derivatives/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC6493204
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Endothelial nitric oxide synthase
OT  - Ischemia/reperfusion
OT  - Nitric oxide
COIS- The authors declare no conflict of interest.
EDAT- 2014/01/09 06:00
MHDA- 2014/09/10 06:00
PMCR- 2014/01/08
CRDT- 2014/01/09 06:00
PHST- 2013/03/22 00:00 [received]
PHST- 2013/09/05 00:00 [revised]
PHST- 2013/09/06 00:00 [accepted]
PHST- 2014/01/09 06:00 [entrez]
PHST- 2014/01/09 06:00 [pubmed]
PHST- 2014/09/10 06:00 [medline]
PHST- 2014/01/08 00:00 [pmc-release]
AID - CNS12182 [pii]
AID - 10.1111/cns.12182 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2014 Feb;20(2):154-64. doi: 10.1111/cns.12182. Epub 2014 Jan 
      8.