Matrix Metalloproteinase-8 is a Novel Pathogenetic Factor in Focal Cerebral Ischemia
| العنوان: | Matrix Metalloproteinase-8 is a Novel Pathogenetic Factor in Focal Cerebral Ischemia |
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| المؤلفون: | Eunjung Moon, Ji Woong Choi, Hee Sun Kim, Eun Jung Lee, Jong Hoon Ryu, Jeong Eun Han |
| المصدر: | Molecular Neurobiology. 53:231-239 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Neuroscience (miscellaneous), Ischemia, Down-Regulation, Brain damage, MMP8, Brain Ischemia, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Downregulation and upregulation, medicine, Animals, Claudin-5, RNA, Small Interfering, Neuroinflammation, Inflammation, Mice, Inbred ICR, Microglia, business.industry, Lentivirus, Neutrophil collagenase, Brain, Infarction, Middle Cerebral Artery, medicine.disease, Up-Regulation, Matrix Metalloproteinase 8, 030104 developmental biology, medicine.anatomical_structure, Neurology, Blood-Brain Barrier, Reperfusion, Tumor necrosis factor alpha, medicine.symptom, business, 030217 neurology & neurosurgery |
| الوصف: | 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. |
| تدمد: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-014-8996-y |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc45aebdf1a4e489d25f1db354471506 https://doi.org/10.1007/s12035-014-8996-y |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....cc45aebdf1a4e489d25f1db354471506 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15591182 08937648 |
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| DOI: | 10.1007/s12035-014-8996-y |