PMID- 26398857
OWN - NLM
STAT- MEDLINE
DCOM- 20160811
LR  - 20181113
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 12
IP  - 5
DP  - 2015 Nov
TI  - Combination of early and delayed ischemic postconditioning enhances brain-derived 
      neurotrophic factor production by upregulating the ERK-CREB pathway in rats with 
      focal ischemia.
PG  - 6427-34
LID - 10.3892/mmr.2015.4327 [doi]
AB  - Ischemic postconditioning, including early and delayed ischemic postconditioning, 
      has been recognized as a simple and promising strategy in the treatment of 
      stroke. However, the effects of the combination of early and delayed ischemic 
      postconditioning, and the mechanisms underlying these effects, remain unclear. 
      The aim of the present study was to determine whether the combination of early 
      and delayed ischemic postconditioning offers greater protection against stroke, 
      and enhances the production of brain‑derived neurotrophic factor (BDNF). A 
      combination of early and delayed ischemic postconditioning was established by 
      repeated, transient occlusion and reperfusion of the ipsilateral common carotid 
      artery in a rat model of middle cerebral artery occlusion. Infarct size, motor 
      function, cerebral blood flow and brain edema were then evaluated, in order to 
      confirm the effects of combinative ischemic postconditioning. TUNEL staining was 
      used to analyze the rate of apoptosis of cells in the penumbral area. BDNF, 
      extracellular signal‑regulated kinases 1/2 (ERK1/2) and cAMP response 
      element‑binding protein (CREB) expression was detected using immunofluorescence 
      staining and western blot analysis. The results of the present study indicated 
      that the combination of early and delayed ischemic postconditioning further 
      reduced the infarct volume, stabilized cerebral blood disturbance and attenuated 
      neuronal apoptosis, compared with either alone. However, combinative 
      postconditioning exerted the same effect on neurological function and brain 
      edema, compared with early or delayed ischemic postconditioning alone. Further 
      investigation indicated that combinative ischemic postconditioning increased the 
      expression of BDNF, and a significantly higher number of BDNF‑positive cells was 
      observed in neurons and astrocytes from the combined group than in the early or 
      delayed groups. Combinative ischemic postconditioning also induced the 
      phosphorylation of ERK1/2 and CREB in the cortex, following focal ischemia. The 
      results of the present study suggest that the combination of early and delayed 
      ischemic postconditioning may further reduce brain ischemic reperfusion injury 
      following focal ischemia, compared with either treatment alone. In addition, it 
      induces the production of BDNF in neurons and astrocytes. Furthermore, the 
      effects of combinative ischemic postconditioning may be mediated by the 
      activation of ERK1/2 and CREB.
FAU - Wu, Hui
AU  - Wu H
AD  - Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai 201112, P.R. China.
FAU - Yang, Shao-Feng
AU  - Yang SF
AD  - Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai 201112, P.R. China.
FAU - Dai, Jiong
AU  - Dai J
AD  - Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai 201112, P.R. China.
FAU - Qiu, Yong-Ming
AU  - Qiu YM
AD  - Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai 201112, P.R. China.
FAU - Miao, Yi-Feng
AU  - Miao YF
AD  - Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai 201112, P.R. China.
FAU - Zhang, Xiao-Hua
AU  - Zhang XH
AD  - Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai 201112, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150915
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Astrocytes/metabolism/pathology
MH  - Brain Edema/etiology/*genetics/pathology/therapy
MH  - Brain Ischemia/etiology/*genetics/pathology/therapy
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Cerebral Cortex/metabolism/pathology
MH  - Cyclic AMP Response Element-Binding Protein/*genetics/metabolism
MH  - Gene Expression Regulation
MH  - Infarction, Middle Cerebral Artery/complications/surgery
MH  - Ischemic Postconditioning/methods
MH  - MAP Kinase Signaling System
MH  - Male
MH  - Mitogen-Activated Protein Kinase 1/*genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/*genetics/metabolism
MH  - Neurons/metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stroke/etiology/*genetics/pathology/therapy
MH  - Time Factors
PMC - PMC4626133
EDAT- 2015/09/24 06:00
MHDA- 2016/08/12 06:00
PMCR- 2015/09/15
CRDT- 2015/09/24 06:00
PHST- 2014/07/29 00:00 [received]
PHST- 2015/04/15 00:00 [accepted]
PHST- 2015/09/24 06:00 [entrez]
PHST- 2015/09/24 06:00 [pubmed]
PHST- 2016/08/12 06:00 [medline]
PHST- 2015/09/15 00:00 [pmc-release]
AID - mmr-12-05-6427 [pii]
AID - 10.3892/mmr.2015.4327 [doi]
PST - ppublish
SO  - Mol Med Rep. 2015 Nov;12(5):6427-34. doi: 10.3892/mmr.2015.4327. Epub 2015 Sep 
      15.