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. 2015 May 15;31(5):550–560. doi: 10.1007/s12264-015-1533-1

Hypoxia-controlled matrix metalloproteinase-9 hyperexpression promotes behavioral recovery after ischemia

Hongxia Cai 1,2, Zhihao Mu 1,2, Zhen Jiang 1,2, Yongting Wang 2, Guo-Yuan Yang 1,2,✉, Zhijun Zhang 2,✉
PMCID: PMC5563676  PMID: 25975730

Abstract

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 hypoxia-controlled 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.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s12264-015-1533-1 and is accessible for authorized users.

Keywords: blood-brain barrier, hypoxia response element, matrix metalloproteinase 9, stroke

Electronic supplementary material

12264_2015_1533_MOESM1_ESM.pdf (246.2KB, pdf)

Supplementary material, approximately 246 KB.

Footnotes

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s12264-015-1533-1 and is accessible for authorized users.

Contributor Information

Guo-Yuan Yang, Email: gyyang0626@gmail.com.

Zhijun Zhang, Email: zhangzhij@gmail.com.

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12264_2015_1533_MOESM1_ESM.pdf (246.2KB, pdf)

Supplementary material, approximately 246 KB.

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