Abstract
Exogenous delivery of the neurotrophin-3 (NT-3) gene may provide a potential therapeutic strategy for ischemic 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 90min of transient middle cerebral artery occlusion (tMCAO), followed by 1–28days 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 7days after tMCAO. Furthermore, the neurological status of RV-5H-NT3-transduced rats was better than that of RV-5H-EGFP- or saline-transduced animals from 1day to 4weeks after tMCAO. Our results demonstrated that 5HRE could modulate NT-3 expression in the ischemic brain environment and that the up-regulated NT-3 could effectively improve neurological status following tMCAO due to decreased initial damage. To avoid unexpected side effects, 5HRE-controlled gene expression might be a useful tool for gene therapy of ischemic disorders in the central nervous system.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
