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| Content Provider | Springer Nature Link |
|---|---|
| Author | Han, Jeong Eun Lee, Eun Jung Moon, Eunjung Ryu, Jong Hoon Choi, Ji Woong Kim, Hee Sun |
| Copyright Year | 2014 |
| Abstract | The neutrophil collagenase matrix metalloproteinase-8 (MMP8) is a recently identified member of MMPs that have important roles in various inflammation-related disorders. Previously, we identified MMP8 as a new neuroinflammatory mediator in activated microglia by regulating TNF-α productivity. Here, we present evidence that MMP8 is a critical factor for brain damage in transient focal cerebral ischemia by modulating neuroinflammation likely microglial activation and TNF-α production. Biochemical analyses showed upregulation of MMP8 expression at mRNA and protein levels in transient middle cerebral artery occlusion/reperfusion (M/R)-challenged brains. Furthermore, double immunolabeling showed that MMP8 expression was upregulated in the activated microglia of M/R-challenged brains. Assessment of infarct volume, neurological score, and survival/death of neural cells revealed that administration of an MMP8 inhibitor (M8I) immediately after reperfusion reduced brain damage. Histological analyses showed that microglial activation and TNF-α expression in ischemic conditions was abrogated by exposure to M8I, as demonstrated in our previous study using cultured microglia. These outcomes from a pharmacological approach were reaffirmed by a genetic approach using a lentiviral system. Intracerebroventricular microinjection of MMP8-specific shRNA lentivirus reduced the extent of ischemia-induced brain damage, as assessed by infarct volume, neurological score, microglial activation, and TNF-α expression. These results suggest a novel pathogenetic role of MMP8 and implicate modulation of its activity as a tractable strategy for therapies against cerebral ischemia. |
| Starting Page | 231 |
| Ending Page | 239 |
| Page Count | 9 |
| File Format | |
| ISSN | 08937648 |
| Journal | Molecular Neurobiology |
| Volume Number | 53 |
| Issue Number | 1 |
| e-ISSN | 15591182 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2014-11-26 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | MMP8 MMP8 inhibitor MMP8 shRNA Microglia TNF-α Middle cerebral artery occlusion/reperfusion Neurosciences Neurobiology Cell Biology Neurology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Cellular and Molecular Neuroscience |
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