TNF-α knockout and minocycline treatment attenuates blood–brain barrier leakage in MPTP-treated mice
Open accessAbstract
Following intraparenchymal injection of the dopamine (DA) neurotoxin 6-hydroxydopamine, we previously demonstrated passage of fluoresceinisothiocyanate-labeled albumin (FITC-LA) from blood into the substantia nigra (SN) and striatum suggesting damage to the blood-brain barrier (BBB). The factors contributing to the BBB leakage could have included neuroinflammation, loss of DA neuron control of barrier function, or a combination of both. In order to determine which factor(s) was responsible, we assessed BBB integrity using the FITC-LA technique in wild-type (WT), tumor necrosis factor alpha (TNF-alpha) knockout (KO), and minocycline (an inhibitor of microglia activation) treated mice 72 h following treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Compared with WT mice, TNF-alpha KO mice treated with MPTP showed reduced FITC-LA leakage, decreased numbers of activated microglia, and reduced proinflammatory cytokines (TNF-alpha and interleukin 1beta) associated with significant MPTP-induced DA neuron loss. In contrast, minocycline treated animals did not exhibit significant MPTP-induced DA neuron loss although their FITC-LA leakage, numbers of activated microglia, and MPTP-induced cytokines were markedly attenuated. Since both TNF-alpha KO and minocycline treatment attenuated MPTP-induced BBB dysfunction, microglial activation, and cytokine increases, but had differential effects on DA neuron loss, it appears that neuroinflammation and not DA neuron loss was re…
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?
In rodent models of Parkinson's disease induced by MPTP or 6-OHDA, compromised blood-brain barrier integrity is observed, including leakage of FITC-albumin, horseradish peroxidase, and Evan's blue in the substantia nigra and striatum.
“compromised BBB integrity is also observed in rodent models of PD induced by systemic administration of MPTP (108, 680) or intrastriatal administration of 6-hydroxydopamine (6-OHDA) (95), including leakage of fluoresceinisothiocyanate (FITC)-labeled albumin (95, 108, 680), horseradish peroxidase (95), and Evan's blue (108) in the substantia nigra and striatum.”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [680]
Cites
Wu, D. C., Jackson-Lewis, V., Vila, M., Tieu, K., Teismann, P., Vadseth, C., Choi, D.-K., Ischiropoulos, H., & Przedborski, S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-05-01763.2002 · Cited by 1,183 · see citing works
The Potential of Minocycline for Neuroprotection in Human Neurologic Disease
Zemke, D., & Majid, A. (2004) · Clinical Neuropharmacology · doi:10.1097/01.wnf.0000150867.98887.3e · Cited by 125 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969 · see citing works
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
O'Connor, J. C., Lawson, M. A., André, C., Moreau, M., Lestage, J., Castanon, N., Kelley, K. W., & Dantzer, R. (2009) · Molecular Psychiatry · doi:10.1038/sj.mp.4002148 · Cited by 1,278 · see citing works
Inflammation in Parkinson’s Disease: Mechanisms and Therapeutic Implications
Pajares, M., I. Rojo, A., Manda, G., Boscá, L., & Cuadrado, A. (2020) · Cells · doi:10.3390/cells9071687 · Cited by 779 · see citing works
Blood–Brain Barrier Pathology in Alzheimer's and Parkinson's Disease: Implications for Drug Therapy
Desai, B. S., Monahan, A. J., Carvey, P. M., & Hendey, B. (2007) · Cell Transplantation · doi:10.3727/000000007783464731 · Cited by 339 · see citing works
Self-citationTNFα disrupts blood brain barrier integrity to maintain prolonged depressive-like behavior in mice
Cheng, Y., Desse, S., Martinez, A., Worthen, R. J., Jope, R. S., & Beurel, E. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.02.003 · Cited by 292 · see citing works
Losing your nerves? Maybe it's the antibodies
Diamond, B., Huerta, P. T., Mina-Osorio, P., Kowal, C., & Volpe, B. T. (2009) · Nature Reviews Immunology · doi:10.1038/nri2529 · Cited by 247 · see citing works
Brkic, M., Balusu, S., Libert, C., & Vandenbroucke, R. E. (2015) · Mediators of Inflammation · doi:10.1155/2015/620581 · Cited by 205 · see citing works
Caffeine protects against MPTP‐induced blood‐brain barrier dysfunction in mouse striatum
Chen, X., Lan, X., Roche, I., Liu, R., & Geiger, J. D. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05697.x · Cited by 189 · see citing works
Nishioku, T., Matsumoto, J., Dohgu, S., Sumi, N., Miyao, K., Takata, F., Shuto, H., Yamauchi, A., & Kataoka, Y. (2010) · Journal of Pharmacological Sciences · doi:10.1254/jphs.09292sc · Cited by 168 · see citing works
Pan, Y., & Nicolazzo, J. A. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.04.009 · Cited by 131 · see citing works
Chung, Y. C., Kim, Y.-S., Bok, E., Yune, T. Y., Maeng, S., & Jin, B. K. (2013) · Mediators of Inflammation · doi:10.1155/2013/370526 · Cited by 94 · see citing works
Machado, V., Zöller, T., Attaai, A., & Spittau, B. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020151 · Cited by 76 · see citing works
γ-Secretase and its modulators: Twenty years and beyond
Xia, W. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.02.011 · Cited by 54 · see citing works
Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease
Reich, N., & Hölscher, C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.614828 · Cited by 48 · see citing works
“For example, the genetic deletion of TNF-α and the utility of the microglial inhibitor minocycline attenuated the MPTP-induced permeabilization of the BBB in this PD animal model (Zhao et al., 2007).”
Li, S., Bi, G., Han, S., & Huang, R. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.744942 · Cited by 45 · see citing works
- Authors
- Zhao, C., Ling, Z., Newman, M. B., Bhatia, A., & Carvey, P. M.
- Affiliations
- Rush University Medical Center (US)
- Corresponding author
- Carvey, Paul M.
- ORCID
- Bhatia, Ankush
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2007-04
- Volume
- 26
- Issue
- 1
- Pages
- 36-46
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC1892817
- OpenAlex
- W1972609039
- Cited by
- 183
- References
- 2
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 12 · 2023: 8 · 2022: 9 · 2021: 11 · 2020: 8 · 2019: 8 · 2018: 10 · 2017: 5 · 2016: 7 · 2015: 10 · 2014: 12 · 2013: 13 · 2012: 8
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- National Institute of Neurological Disorders and Stroke (NS045316)
- National Institute of Environmental Health Sciences (012307, W81XWH-04-01-0365)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- blood-brain barrier disruption, MPTP, neuroinflammation, TNF-α, minocycline, microglial activation, dopamine neuron loss, 6-hydroxydopamine, IL-1β, inflammatory cytokines, substantia nigra, striatum, Parkinson's disease
- MeSH terms
- Animals, Anti-Bacterial Agents, Blood-Brain Barrier, Cell Count, Dopamine, Enzyme-Linked Immunosorbent Assay, Fluorescent Dyes, Immunohistochemistry, Male, Mice, Inbred C57BL, Minocycline, Neurons, Permeability, Substantia Nigra, Tumor Necrosis Factor-alpha, Fluorescein-5-isothiocyanate, Neostriatum, Microglia, Mice, Knockout, MPTP Poisoning, Mice, Interleukin-1beta
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
