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

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.

Effect of ischaemic brain injury on sexual function in adult mice

Objective:Priapism refers to a condition with persistent abnormal erection of the penis,which is usually caused by disease or injury in the brain or spinal cord,or obstruction to the outflow of blood through the dorsal vein at the root of the penis,without sexual desires.The effect of cerebral ischaemia on sexual function is unknown.The aim of this study is to explore whether priapism occurs in adult mice.Furthermore,we examined the relationship between priapism and the region of infarct in the brain.Design:Adult male CD-1 mice who underwent permanent middle cerebral artery occlusion(pMCAO)were closely examined from 2 hours to 14 days postoperation.Results:We found that priapism occurs in∼80%of the mice with pMCAO,which could persist up to 14 days.Further study has demonstrated that the occurrence of priapism is related to the infarct region:priapism is found only in mice with ischaemic injury extending to the hypothalamus and the hippocampus regions.Conclusion:Our result suggested priapism may be used as a deep brain injury marker for evaluating brain injury in mice after pMCAO.