PMID- 19703519
OWN - NLM
STAT- MEDLINE
DCOM- 20100104
LR  - 20121115
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 465
IP  - 3
DP  - 2009 Nov 20
TI  - Adenovirus-mediated brain-derived neurotrophic factor expression regulated by 
      hypoxia response element protects brain from injury of transient middle cerebral 
      artery occlusion in mice.
PG  - 220-5
LID - 10.1016/j.neulet.2009.08.049 [doi]
AB  - Some gene expression may be regulated by hypoxia-responsive element (HRE) that is 
      bound by hypoxia-inducible factor-1 (HIF-1) which is up-regulated during cerebral 
      ischemia. To explore ischemia/hypoxia-controlled expression and the 
      neuroprotective effects of brain-derived neurotrophic factor (BDNF) after 
      ischemic brain injury, an adenoviral vector using five copies of hypoxia response 
      element (HRE) in the vascular endothelial growth factor gene to regulate the 
      expression of BDNF gene (Ad5HRE:BDNF) was constructed, and its efficacy was 
      verified for driving BDNF expression in cultured Hela cells under hypoxic 
      condition by ELISA. We found that the concentration of BDNF in the 
      Ad5HRE:BDNF-transfected culture media was 28-fold greater in a hypoxic condition 
      than under normoxia. To examine the effect of Ad5HRE:BDNF on ischemic brain 
      injury in vivo, Ad5HRE:BDNF was injected into right caudate putamen of adult mice 
      7 days prior to 60 min transient middle cerebral artery occlusion (MCAO). It was 
      found that exogenous BDNF expression was increased in the Ad5HRE-BDNF-treated 
      group and infarct volume of the Ad5HRE:BDNF-treated group at 3 days after MCAO 
      was significantly smaller than that of vehicle- or AdNull-treated groups. 
      Moreover, Ad5HRE:BDNF injection resulted in significantly improved sensorimotor 
      scores 7 days after MCAO and induced a reduction in the number of Fluoro-Jade 
      B-positive neurons and TUNEL-positive cells, compared with vehicle- or 
      AdNull-injection. Our findings suggest that BDNF expression could be regulated in 
      hypoxia/ischemia condition with five copies of HRE and ameliorates ischemic brain 
      injury in a mouse focal cerebral ischemia model.
FAU - Shi, Qindong
AU  - Shi Q
AD  - The Institute of Neurobiology, Enviroment and Genes Related to Diseases Key 
      laboratory of Education Ministry, the State Key Subject for Physiology, Xi'an 
      Jiaotong University College of Medicine, Xi'an, Shaanxi, 710061, PR China.
FAU - Zhang, Pengbo
AU  - Zhang P
FAU - Zhang, Junfeng
AU  - Zhang J
FAU - Chen, Xinlin
AU  - Chen X
FAU - Lu, Haixia
AU  - Lu H
FAU - Tian, Yumei
AU  - Tian Y
FAU - Parker, T L
AU  - Parker TL
FAU - Liu, Yong
AU  - Liu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090822
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Brain Ischemia/genetics/*metabolism/*prevention & control
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism/*therapeutic use
MH  - Gene Expression Regulation
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/genetics
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Infarction, Middle Cerebral Artery/complications/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Transfection/methods
MH  - Treatment Outcome
EDAT- 2009/08/26 09:00
MHDA- 2010/01/05 06:00
CRDT- 2009/08/26 09:00
PHST- 2009/03/09 00:00 [received]
PHST- 2009/08/16 00:00 [revised]
PHST- 2009/08/18 00:00 [accepted]
PHST- 2009/08/26 09:00 [entrez]
PHST- 2009/08/26 09:00 [pubmed]
PHST- 2010/01/05 06:00 [medline]
AID - S0304-3940(09)01141-0 [pii]
AID - 10.1016/j.neulet.2009.08.049 [doi]
PST - ppublish
SO  - Neurosci Lett. 2009 Nov 20;465(3):220-5. doi: 10.1016/j.neulet.2009.08.049. Epub 
      2009 Aug 22.