期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 28, 期 10, 页码 1674-1685出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2008.59
关键词
cerebral ischemia; matrix metalloproteinases; tissue inhibitor of matrix metalloproteinases; vasogenic edema
Enhanced matrix metalloproteinases (MMPs) can cause vasogenic edema and hemorrhagic transformation after cerebral ischemia, and affect the extent of ischemic injury. We hypothesized that the endogenous MMP inhibitors, tissue inhibitor of MMPs (TIMPs), were essential to protect against blood-brain barrier (BBB) disruption after ischemia by regulating the activities of MMPs. We confirmed the transition of MMP-2 and MMP-9, and the TIMPs family after 30 mins of middle cerebral artery occlusion, and elucidated the function of TIMP-1 and TIMP-2 in focal ischemia, using TIMP-1-/- and TIMP-2(-/)-mice. TIMP-1 mRNA expression was gradually increased until 24 h after reperfusion. In TIMP-1(-/)-mice, MMP-9 protein expression and gelatinolytic activity were significantly more augmented after cerebral ischemia than those in WT mice, and were accompanied by exacerbated BBB disruption, neuronal apoptosis, and ischemic injury. In contrast, TIMP-2 gene deletion mice exhibited no significant difference in MMP expressions and the degree of ischemic injury despite an increased Evans blue leakage. These results suggest that TIMP-1 inhibits MMP-9 activity and can play a neuroprotective role in cerebral ischemia.
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