Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral artery occlusion
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Haiyan LU1, MD, Yongting WANG1, PhD, Falei YUAN1, MS, Jianrong LIU2, MD, Lili ZENG1,2, MD, Guo-Yuan YANG 1,2, MD, PhD
- چاپ و سال / کشور: 2011
Description
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.
Front. Med. 2011, 5(1): 86–93 DOI 10.1007/s11684-011-0118-x Higher Education Press and Springer-Verlag Berlin Heidelberg 2011
