Cited by 102Traumatic Brain Injury and Neurovascular DisturbancesMitochondrial Function and PathologyTraumatic Brain Injury Research

Mitochondrial division inhibitor 1 (Mdivi-1) offers neuroprotection through diminishing cell death and improving functional outcome in a mouse model of traumatic brain injury

Wu, Qiong, Xia, Shui-Xiu, Li, Qian-Qian, Gao, Yuan, Shen, Xi, Ma, Lu, Zhang, Ming-Yang, Wang, Tao +4 more·2016·Brain Research

Abstract

Mitochondria dysfunction, an enormous potential crisis, has attracted increasing attention. Disturbed regulation of mitochondrial dynamics, the balance of mitochondrial fusion and fission, has been implicated in neurodegenerative diseases, such as Parkinson׳s disease and cerebral ischemia/reperfusion. However the role of mitochondrial dynamics in traumatic brain injury (TBI) has not been illuminated. The aim of the present study was to investigate the role of Mdivi-1, a small molecule inhibitor of a key mitochondrial fission protein dynamin-related protein 1 (Drp1), in TBI-induced cell death and functional outcome deficits. Protein expression of Drp1 was first investigated. Outcome parameters consist of motor test, Morris water maze, brain edema and lesion volume. Cell death was detected by propidium iodide (PI) labeling, and mitochondrial morphology was assessed using transmission electron microscopy. In addition, the expression of apoptosis-related proteins cytochrome c (cyt-c) and caspase-3 was investigated. Our findings showed that up-regulation of Drp1 expression started at 1h post-TBI and peaked at 24 h, but inhibition of Drp1 by Mdivi-1 significantly alleviated TBI-induced behavioral deficits and brain edema, reduced morphological change of mitochondria, and decreased TBI-induced cell death together with lesion volume. Moreover, treatment with Mdivi-1 remarkably inhibited TBI-induced the release of cyt-c from mitochondria to cytoplasm, and activation of caspase-3 at 24 h after TBI. Taken together, these data imply that inhibition of Drp1 may help attenuate TBI-induced functional outcome and cell death through maintaining normal mitochondrial morphology and inhibiting activation of apoptosis.

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Crossref · 10.1016/j.brainres.2015.11.016

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Authors
Wu, Q., Xia, S.-X., Li, Q.-Q., Gao, Y., Shen, X., Ma, L., Zhang, M.-Y., Wang, T., Li, Y.-S., Wang, Z.-F., Luo, C.-L., & Tao, L.-Y.
Affiliations
Soochow University (CN)
Corresponding author
Luo, Cheng-Liang
Venue
Brain Research
Publisher
Elsevier BV
Published
2016-01
Volume
1630
Pages
134-143
ISSN
0006-8993 (ISSN-L)
OpenAlex
W2179947625
Cited by
102
References
39
Citations by year
2026: 3 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 8 · 2021: 8 · 2020: 19 · 2019: 15 · 2018: 14 · 2017: 13 · 2016: 7
FWCI
7.99
Type
journal article
Language
en
Open access
closed
Locations
  • Brain Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81400999, 81172911, 81373251, 81530062)
  • China Postdoctoral Science Foundation (2014M551660)
  • Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
Mdivi-1, traumatic brain injury, mitochondrial fission, Drp1, mitochondrial dynamics, neuroprotection, apoptosis, cytochrome c release, caspase-3, cerebral edema, lesion volume, mitochondrial morphology, functional outcome
MeSH terms
Animals, Brain, Brain Edema, Brain Injuries, Disease Models, Animal, Male, Mice, Inbred ICR, Mitochondria, Motor Activity, Random Allocation, Cell Death, Neuroprotective Agents, Maze Learning, Recovery of Function, Dynamins, Cytochromes c, Quinazolinones, Caspase 3

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