- Meeting abstract
- Open Access
Retrovirus mediated hypoxia-responsive element-regulated neurotrophin-3 transduction attenuates brain injury following focal cerebral ischemia in rats
© Zhang et al; licensee BioMed Central Ltd. 2012
- Published: 7 February 2012
- Functional Recovery
- Middle Cerebral Artery Occlusion
- Infarct Volume
- Saline Group
- TUNEL Positive Cell
Exogenous delivery of Neurotrophin-3 (NT-3) gene may provide a potential therapeutic strategy for ischemic stroke. But uncontrolled expression of NT-3 may cause deleterious side effects. Recently, hypoxia-specific gene expression systems have been developed in various ischemic diseases. To explore ischemia/hypoxia-controlled expression of NT-3 in rats, we constructed a recombinant retrovirus vector with 5HRE and NT-3 and delivered it to rat brain to investigate the neuroprotective effects of hypoxia induced NT-3 overexpression on focal cerebral ischemia.
Three groups of rats received RV-5H-NT3, RV-5H-EGFP or saline injection, respectively. 3 days after gene transfer, the rats underwent 90 minutes of transient middle cerebral artery occlusion (tMCAO) and followed by 1 to 14 days reperfusion. Expression of NT-3 was detected by immunohistochemical staining and Western blot; neurological function was assessed by sensorimotor behavioral tests; infarct volume was determined by TTC staining; neuronal injury was examined by TUNEL.
NT-3 expression was significantly increased in RV-5H-NT3 transduced rat brain compared with RV-5H-EGFP or saline group 3 days after tMCAO (P < 0.05). Infarct volume was smaller in RV-5H-NT3 transduced rat brain than RV-5H-EGFP or saline group (P < 0.05) with reduced percentage of TUNEL positive cells (P < 0.05). Furthermore, functional recovery in RV-5H-NT3 transduced rats was better than RV-5H-EGFP or saline transduced group from 1 day to 2 weeks after tMCAO (P < 0.05).
After RV-5H-NT3 gene transfer, NT-3 expression was up-regulated by five copies of HRE in response to hypoxia/ischemia, and hypoxia-regulated NT-3 expression attenuates ischemic brain injury and promotes functional recovery in cerebral ischemia rats.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.