Journal
CELLULAR AND MOLECULAR NEUROBIOLOGY
Volume 41, Issue 8, Pages 1651-1663Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-020-00933-z
Keywords
Traumatic brain injury; Blood-brain barrier; MMP-9; Mitophagy; Parkinson's disease
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Funding
- National Natural Science Foundation of China [81901258, 81972153]
- National Natural Science Foundation of Zhenjiang [SH2019030]
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Concussion can cause disruption of the blood-brain barrier through MMP-9, with the MMP-9 inhibitor GM6001 preventing the development of PD via the autophagy pathway.
Concussion is a widely recognized environmental risk factor for neurodegenerative diseases, including Parkinson's disease (PD). Small-vessel disease of the brain has been reported to contribute to neurodegenerative diseases. In this study, we observed BBB disruption in wild-type (WT) mice, but not in matrix metalloproteinase 9 (MMP-9) knockout mice, subjected to single severe traumatic brain injury (ssTBI). Furthermore, treating ssTBI mice with the MMP-9 inhibitor GM6001 effectively maintained BBB integrity, promoted the elimination of damaged mitochondria via mitophagy, and then prevented neuronal death and progressive neurodegeneration. However, we did not observe this neuroprotective effect of MMP-9 inhibition in beclin-1(-/+)mice. Collectively, these findings revealed that concussion led to BBB disruption via MMP-9, and that GM6001 prevented the development of PD via the autophagy pathway.
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