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.

journal_name

Front Med

journal_title

Frontiers of medicine

authors

Lu H,Wang Y,Yuan F,Liu J,Zeng L,Yang GY

doi

10.1007/s11684-011-0118-x

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

86-93

issue

1

eissn

2095-0217

issn

2095-0225

journal_volume

5

pub_type

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