NEUROPROTECTION OF NEUROTROPHIN-3 AGAINST FOCAL CEREBRAL ISCHEMIA/REPERFUSION INJURY IS REGULATED BY HYPOXIA-RESPONSIVE ELEMENT IN RATS

摘要

Exogenous delivery of the neurotrophin-3 (NT-3) gene may provide a potential therapeutic strategy for ische-mic stroke. To investigate the neuroprotective effects of NT-3 expression controlled by 5HRE after focal cerebral ischemia, we constructed a recombinant retrovirus vector (RV) with five copies of hypoxia-responsive elements (5HRE or 5H) and NT-3 and delivered it to the rat brain. Three groups of rats received RV-5H-NT3, RV-5H-EGFP or saline injection. Three days after gene transfer, the rats underwent 90 min of transient middle cerebral artery occlusion (tMCAO), followed by 1-28 days of reperfusion. Three days after tMCAO, brain NT-3 expression was significantly increased in the RV-5H-NT3-transduced animals compared with the RV-5H-EGFP or saline group, and brain infarct volume was smaller in the RV-5H-NT3-transduced group than the RV-5H-EGFP or saline group. The percentage of TUNEL-positive cells was reduced in RV-5H-NT3-transduced brains compared with the RV-5H-EGFP or saline group 3 and 7 days after tMCAO.