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Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral artery occlusion.

Abstract
Netrin-1 (NT-1) is one of the axon-guiding molecules that are critical for neuronal development. Because of its structural homology to the endothelial mitogens, NT-1 may have similar effects on vascular network formation. NT-1 was shown to be able to stimulate the proliferation and migration of human cerebral endothelial cells in vitro and also promote focal neovascularization in adult brain in vivo. In the present study, we reported the delivery of NT-1 using an adeno-associated virus (AAV) vector (AAV-NT-1) into mouse brain followed by transient middle cerebral artery occlusion (tMCAO). We found that AAV vectors did not elicit a detectable inflammatory response, cell loss or neuronal damage after brain transduction. The level of NT-1 was increased in the AAV-NT-1-transduced tMCAO mice compared with the control mice. Furthermore, the neurobehavioral outcomes were significantly improved in AAV-NT-1-transduced mice compared with the control animals (P<0.05) 7 days after tMCAO. Our data suggests that NT-1 plays a neuronal function recovery role in ischemic brain and that NT-1 gene transfer might present a valuable approach to treat brain ischemic disorders.
AuthorsHaiyan Lu, Yongting Wang, Falei Yuan, Jianrong Liu, Lili Zeng, Guo-Yuan Yang
JournalFrontiers of medicine (Front Med) Vol. 5 Issue 1 Pg. 86-93 (Mar 2011) ISSN: 2095-0225 [Electronic] China
PMID21681680 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • NTN1 protein, human
  • Nerve Growth Factors
  • Ntn1 protein, mouse
  • Tumor Suppressor Proteins
  • Netrin-1
Topics
  • Animals
  • Blotting, Western (methods)
  • Brain (blood supply)
  • Chickens
  • Dependovirus (genetics)
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Genetic Vectors
  • Infarction, Middle Cerebral Artery (genetics, therapy)
  • Male
  • Mice
  • Neovascularization, Physiologic
  • Nerve Growth Factors (administration & dosage, physiology)
  • Netrin-1
  • Recovery of Function
  • Tumor Suppressor Proteins (administration & dosage, physiology)

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