摘要
Matrix metalloproteinase-9（MMP-9） plays a beneficial role in the sub-acute phase after ischemic stroke.However,unrestrained MMP-9 may disrupt the blood-brain barrier（BBB）,which has limited its use for the treatment of brain ischemia.In the present study,we constructed lentivirus mediated hypoxiacontrolled MMP-9 expression and explored its role after stroke.Hypoxia response element（HRE）was used to confine MMP-9 expression only to the hypoxic region of mouse brain after 120-min transient middle cerebral artery occlusion.Lentiviruses were injected into the peri-infarct area on day 7 after transient ischemia.We found hyperexpression of exogenous HRE-MMP-9 under the control of hypoxia,and its expression was mainly located in neurons and astrocytes without aggravation of BBB damage compared to the CMV group.Furthermore,mice in the HRE-MMP-9 group showed the best behavioral recovery compared with the normal saline,GFP,and SB-3CT groups.Therefore,hypoxia-controlled MMP-9 hyperexpression during the sub-acute phase of ischemia may provide a novel promising approach of gene therapy for stroke.
Matrix metalloproteinase-9（MMP-9） plays a beneficial role in the sub-acute phase after ischemic stroke.However,unrestrained MMP-9 may disrupt the blood-brain barrier（BBB）,which has limited its use for the treatment of brain ischemia.In the present study,we constructed lentivirus mediated hypoxiacontrolled MMP-9 expression and explored its role after stroke.Hypoxia response element（HRE）was used to confine MMP-9 expression only to the hypoxic region of mouse brain after 120-min transient middle cerebral artery occlusion.Lentiviruses were injected into the peri-infarct area on day 7 after transient ischemia.We found hyperexpression of exogenous HRE-MMP-9 under the control of hypoxia,and its expression was mainly located in neurons and astrocytes without aggravation of BBB damage compared to the CMV group.Furthermore,mice in the HRE-MMP-9 group showed the best behavioral recovery compared with the normal saline,GFP,and SB-3CT groups.Therefore,hypoxia-controlled MMP-9 hyperexpression during the sub-acute phase of ischemia may provide a novel promising approach of gene therapy for stroke.
基金
supported by the grants from the National Natural Science Foundation of China (U1232205)
the National Basic Research Development Program (973 Program) of China (2011CB504405)
the Science and Technology Commission of Shanghai Municipality, China (13140903500 and 13ZR1422600)
Shanghai Jiao Tong University Foundation for Technological Innovation in Major Projects (12X190030021)
the KC Wong Foundation
