Volume 7 Supplement 1

Proceedings of the 2011 International Conference on Molecular Neurodegeneration

Open Access

Retrovirus mediated hypoxia-responsive element-regulated neurotrophin-3 transduction attenuates brain injury following focal cerebral ischemia in rats

  • Junfeng Zhang1,
  • Qindong Shi1,
  • Pengbo Yang1,
  • Xi Xu1,
  • Xinlin Chen1,
  • Cunfang Qi1,
  • Jianshui Zhang1,
  • Haixia Lu1,
  • Pengbo Zhang1,
  • Bingqiao Zhao2,
  • Ping Zheng2 and
  • Yong Liu1
Molecular Neurodegeneration20127(Suppl 1):S16

https://doi.org/10.1186/1750-1326-7-S1-S16

Published: 7 February 2012

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Authors’ Affiliations

(1)
Institute of Neurobiology, Xi’an Jiaotong University College of Medicine
(2)
The State Key Laboratory of Medical Neurobiology

Copyright

© Zhang et al; licensee BioMed Central Ltd. 2012

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.

Advertisement