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.