title: 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.
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lu
authors.forename: Yongting
authors.initials: Y
authors.lastname: Wang
authors.forename: Falei
authors.initials: F
authors.lastname: Yuan
authors.forename: Jianrong
authors.initials: J
authors.lastname: Liu
authors.forename: Lili
authors.initials: L
authors.lastname: Zeng
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000098:blood supply*; D002645:Chickens; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000628:therapy*; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000502:physiology*; D000075388:Netrin-1; D020127:Recovery of Function; D025521:Tumor Suppressor Proteins / Q000008:administration & dosage / Q000502:physiology*
chemical_list: C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1