Mitochondrial dynamics and protective effects of a mitochondrial division inhibitor, Mdivi-1, in lipopolysaccharide-induced brain damage
Abstract
Sepsis is one of the most common reasons for mortality in Intensive Care Units. As a common but severe neurological complication, sepsis associated encephalopathy (SAE) has always been ignored and there is no generally accepted treatment. In this study, we demonstrated that Mdivi-1 ameliorated brain damage assessed by Nissl staining. Furthermore, Mdivi-1 reduced TUNEL-positive cells in hippocampus, and inhibited S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE) release into plasma. Biochemical analysis also showed that Mdivi-1 protected hippocampus from oxidative stresses. Western blot analysis revealed that Mdivi-1, as a Drp1 inhibitor, inhibited LPS induced dynamin-related GTPase (Drp1) increase. Interestingly, it can also attenuate LPS induced optic atrophy 1 (OPA1) and phosphorylated Drp1 (p-Drp1) decrease. Thus Mdivi-1 protected rats from SAE, and this protective effect could be associated with its inhibition of Drp1 and its activation of p-Drp1 and OPA1. Mitochondrial dynamics may be a potential pharmacological therapeutic target for treating SAE.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Our results are consistent with previous studies showing promise for Drp1 inhibitor Mdivi-1, cyclophilin D, and mitochondria-targeting peptide SS-31 in treating SAE.
“Our results are consistent with previous studies showing promise for agents like Drp1 inhibitor Mdivi‐1 (Deng et al. 2018), mitochondrial isomerase cyclophilin D (CypD) (Kobayashi et al. 2022), and mitochondria‐targeting peptide SS‐31 (Wu et al. 2015) in treating SAE.”
From Transcript and Lipid Profile Alterations in Astrocyte‐Neuron Mitochondrial Transfer Under Lipopolysaccharide Exposure: An In Vitro Study (2025) · cites this paper as Deng et al. 2018
Cites
Long-term cognitive impairment and functional disability among survivors of severe sepsis.
Iwashyna, T. J., Ely, E. W., Smith, D. M., & Langa, K. M. (2010) · JAMA · doi:10.1001/jama.2010.1553 · Cited by 2,582 · see citing works
Sepsis-associated encephalopathy
Gofton, T. E., & Young, G. B. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.183 · Cited by 821 · see citing works
Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models
Brooks, C., Wei, Q., Cho, S.-G., & Dong, Z. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37829 · Cited by 735 · see citing works
Mitochondrial Defects and Oxidative Stress in Alzheimer Disease and Parkinson Disease
Yan, M. H., Wang, X., & Zhu, X. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.014 · Cited by 718 · see citing works
Hu, C., Huang, Y., & Li, L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010144 · Cited by 302 · see citing works
Leszek, J., E. Barreto, G., G|siorowski, K., Koutsouraki, E., Ávila-Rodrigues, M., & Aliev, G. (2016) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527315666160202125914 · Cited by 206 · see citing works
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., et al. (2016) · Brain Research · doi:10.1016/j.brainres.2015.11.016 · Cited by 102 · see citing works
Characterization of Sepsis and Sepsis-Associated Encephalopathy
Feng, Q., Ai, Y.-H., Gong, H., Wu, L., Ai, M.-L., Deng, S.-Y., Huang, L., Peng, Q.-Y., & Zhang, L.-N. (2019) · Journal of Intensive Care Medicine · doi:10.1177/0885066617719750 · Cited by 101 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Kan, Y., Wang, H., Lin, H., Li, Y., Pei, S., Cui, Y., Xie, K., Chen, H., & Yu, Y. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70003 · Cited by 8 · see citing works
Su, W., Xie, Z., Bai, X., Li, Z., & Liu, X. (2023) · Brain Sciences · doi:10.3390/brainsci13030478 · Cited by 7 · see citing works
- Authors
- Deng, S., Ai, Y., Gong, H., Feng, Q., Li, X., Chen, C., Liu, Z., Wang, Y., Peng, Q., & Zhang, L.
- Affiliations
- Central South University (CN)
- Corresponding author
- Zhang, Lina
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 496
- Issue
- 3
- Pages
- 865-871
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2791003079
- Cited by
- 39
- References
- 8
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 9 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 2
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- mitochondrial dynamics, Mdivi-1, sepsis-associated encephalopathy, lipopolysaccharide, Drp1, OPA1, mitochondrial fission, mitochondrial fusion, hippocampal neuroprotection, oxidative stress, S100B, neuron-specific enolase, neuroinflammation
- MeSH terms
- Animals, Brain, Dose-Response Relationship, Drug, Lipopolysaccharides, Male, Mitochondria, Treatment Outcome, Rats, Sprague-Dawley, Neuroprotective Agents, Dynamins, Rats, Quinazolinones, Sepsis-Associated Encephalopathy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
