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Cited by 49Protease and Inhibitor MechanismsAcute Ischemic Stroke ManagementNeuroinflammation and Neurodegeneration Mechanisms

Post-transcriptional inactivation of matrix metalloproteinase-12 after focal cerebral ischemia attenuates brain damage

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Chelluboina, Bharath, Warhekar, Aditi, Dillard, Matt, Klopfenstein, Jeffrey D., Pinson, David M., Wang, David Z., Veeravalli, Krishna Kumar·2015·Scientific Reports
DOI 10.1038/srep09504PMC PMC5386183
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Abstract

This study highlights the possible pathological role of MMP-12 in the context of ischemic stroke. Male rats were subjected to a two-hour middle cerebral artery occlusion (MCAO) procedure. MMP-12 shRNA expressing plasmid formulation was administered to these rats twenty-four hours after reperfusion. The results showed a predominant upregulation of MMP-12 (approximately 47, 58, 143 and 265 folds on days 1, 3, 5, 7 post-ischemia, respectively) in MCAO subjected rats. MMP-12 expression was localized to neurons, oligodendrocytes and microglia, but not astrocytes. Transcriptional inactivation of MMP-12 significantly reduced the infarct size. The percent infarct size was reduced from 62.87 ± 4.13 to 34.67 ± 5.39 after MMP-12 knockdown compared to untreated MCAO subjected rats. Expression of myelin basic protein was increased and activity of MMP-9 was reduced in ischemic rat brains after MMP-12 knockdown. Furthermore, a significant reduction in the extent of apoptosis was noticed after MMP-12 knockdown. TNFα expression in the ipsilateral regions of MCAO-subjected rats was reduced after MMP-12 knockdown in addition to the reduced protein expression of apoptotic molecules that are downstream to TNFα signaling. Specific knockdown of MMP-12 after focal cerebral ischemia offers neuroprotection that could be mediated via reduced MMP-9 activation and myelin degradation as well as inhibition of apoptosis.

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  • Psmb8 and Mmp12 are associated with detrimental roles in the brain.

    “Conversely, the proteasome subunit (Psmb8) and matrix metalloproteinase-12 (Mmp12) are associated with detrimental roles in the brain [25,26].”

    From TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo (2023) · cites this paper as [26]

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Cited by

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Authors
Chelluboina, B., Warhekar, A., Dillard, M., Klopfenstein, J. D., Pinson, D. M., Wang, D. Z., & Veeravalli, K. K.
Affiliations
Peoria campus of the University of Illinois System (US)
Corresponding author
Veeravalli, Krishna Kumar
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2015-05-08
Volume
5
Issue
1
Pages
9504-9504
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep09504
PMC
PMC5386183
OpenAlex
W637491521
Cited by
49
References
0
Citations by year
2026: 7 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 3 · 2015: 1
FWCI
1.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
matrix metalloproteinase-12, focal cerebral ischemia, ischemic stroke, neuroprotection, middle cerebral artery occlusion, MMP-9, myelin degradation, apoptosis, TNF-α, infarct size, oligodendrocytes, microglia, neurons
MeSH terms
Animals, Brain Injuries, Brain Ischemia, Myelin Basic Protein, Male, Neurons, Plasmids, Substrate Specificity, Transcription, Genetic, Tumor Necrosis Factor-alpha, Reperfusion, Up-Regulation, Rats, Sprague-Dawley, Apoptosis, Matrix Metalloproteinase 9, Gene Silencing, RNA, Small Interfering, Cell Line, Tumor, Matrix Metalloproteinase 12, Gene Knockdown Techniques, Real-Time Polymerase Chain Reaction

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