PMID- 24034153
OWN - NLM
STAT- MEDLINE
DCOM- 20140929
LR  - 20211021
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 20
IP  - 1
DP  - 2014 Jan
TI  - Neuroprotection by sildenafil: neuronal networks potentiation in acute 
      experimental stroke.
PG  - 40-9
LID - 10.1111/cns.12162 [doi]
AB  - AIMS: Sildenafil, a phosphodiesterase type 5 inhibitor, has been found to produce 
      functional recovery in ischemic rats by increasing the cGMP level and triggering 
      neurogenesis. The aim of this study was to investigate further sildenafil 
      mechanisms. METHODS: Male Sprague-Dawley rats underwent middle cerebral artery 
      occlusion and reperfusion, followed by intraperitoneal or intravenous treatment 
      of sildenafil starting 2 h later. Behavioral tests were performed on day 1 or day 
      7 after reperfusion, while cerebral infarction, edema, Nissl staining, 
      Fluoro-Jade B staining, and electron microscopy studies were carried out 24 h 
      poststroke. The cGMP-dependent Nogo-66 receptor (Nogo-R) pathway, synaptophysin, 
      PSD-95/neuronal nitric oxide synthases (nNOS), brain-derived neurotrophic factor 
      (BDNF)/tropomyosin-related kinase B (TrkB), and nerve growth factor 
      (NGF)/tropomyosin-related kinase A (TrkA) were measured. RESULTS: Sildenafil 
      enhanced neurological recovery and inhibited infarction, even following delayed 
      administration 4 h after stroke onset. Furthermore, sildenafil reduced the loss 
      of neurons and modulated the expressions of the cGMP-dependent Nogo-R pathway. 
      Moreover, sildenafil protected the structure of synapses and mediated the 
      expressions of synaptophysin, PSD-95/nNOS, BDNF/TrkB, and NGF/TrkA. CONCLUSIONS: 
      Sildenafil produces significant neuroprotective effects on injured neurons in 
      acute stroke, and these are mediated by the cGMP-dependent Nogo-R pathway, 
      NGF/TrkA, and BDNF/TrkB.
CI  - (c) 2013 John Wiley & Sons Ltd.
FAU - Chen, Xue-Mei
AU  - Chen XM
AD  - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China.
FAU - Wang, Nan-Nan
AU  - Wang NN
FAU - Zhang, Tian-Yu
AU  - Zhang TY
FAU - Wang, Fang
AU  - Wang F
FAU - Wu, Chun-Fu
AU  - Wu CF
FAU - Yang, Jing-Yu
AU  - Yang JY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130830
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, rat)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Myelin Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nogo Receptor 1)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Rtn4r protein, rat)
RN  - 0 (Sulfones)
RN  - 0 (Synaptophysin)
RN  - 0 (Syp protein, rat)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Survival/drug effects
MH  - Disks Large Homolog 4 Protein
MH  - GPI-Linked Proteins/metabolism
MH  - Infarction, Middle Cerebral Artery/*drug therapy/pathology
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Male
MH  - Membrane Proteins/metabolism
MH  - Myelin Proteins/metabolism
MH  - Nerve Growth Factor/metabolism
MH  - Nerve Net/drug effects/physiology
MH  - Neurons/*drug effects/physiology/ultrastructure
MH  - Neuroprotective Agents/administration & dosage/*therapeutic use
MH  - Nitric Oxide Synthase Type I/metabolism
MH  - Nogo Receptor 1
MH  - Piperazines/administration & dosage/*therapeutic use
MH  - Purines/administration & dosage/therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkA/metabolism
MH  - Receptor, trkB/metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - Recovery of Function/drug effects
MH  - Reperfusion Injury/drug therapy/pathology
MH  - Sildenafil Citrate
MH  - Stroke/*drug therapy/pathology
MH  - Sulfones/administration & dosage/*therapeutic use
MH  - Synapses/drug effects/ultrastructure
MH  - Synaptophysin/metabolism
PMC - PMC6493202
OTO - NOTNLM
OT  - Neuronal network
OT  - Neuroprotection
OT  - Sildenafil
OT  - Stroke
COIS- The authors declare no conflict of interest.
EDAT- 2013/09/17 06:00
MHDA- 2014/09/30 06:00
PMCR- 2013/08/30
CRDT- 2013/09/17 06:00
PHST- 2013/03/04 00:00 [received]
PHST- 2013/07/02 00:00 [revised]
PHST- 2013/07/13 00:00 [accepted]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/09/30 06:00 [medline]
PHST- 2013/08/30 00:00 [pmc-release]
AID - CNS12162 [pii]
AID - 10.1111/cns.12162 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2014 Jan;20(1):40-9. doi: 10.1111/cns.12162. Epub 2013 Aug 30.