Blood–brain barrier disruption induces in vivo degeneration of nigral dopaminergic neurons
Abstract
We have evaluated the possibility that changes in the vascular system may constitute a contributing factor for the death of nigral dopaminergic neurons in Parkinson’s disease. Thus, we have employed intranigral injections of vascular endothelial growth factor (VEGF), the most potent inducer of blood–brain barrier (BBB) permeability. A single dose of 1 μg of VEGF, chosen from a dose‐response study, highly disrupted the BBB in the ventral mesencephalon in a time‐dependent manner. A strong regional correlation between BBB disruption and loss of tyrosine hydroxylase‐positive neurons was evident. Moreover, Fluoro‐Jade B labelling showed the presence of dying neurons in the substantia nigra in response to VEGF injection. High number of TUNEL‐positive nuclei was observed in this area along with activation of caspase 3 within nigral dopaminergic neurons. Analysis of the glial population demonstrated a strong inflammatory response and activation of astroglia in response to BBB disruption. We conclude that disruption of the BBB may be a causative factor for degeneration of nigral dopaminergic neurons.
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?
Increased angiogenesis is observed throughout the basal ganglia of 6-OHDA-treated rats.
“Similarly, increased angiogenesis is observed throughout the basal ganglia of 6-OHDA-treated rats (44, 501).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [501]
Blood-brain barrier disruption caused by a single intra-nigral injection of VEGF in rats induces dopaminergic neuron loss in the substantia nigra.
“BBB disruption caused by a single intra-nigral injection of VEGF in rats induces dopaminergic neuron loss in the substantia nigra (501)”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [501]
Cites
McGeer, P. L., Itagaki, S., Boyes, B. E., & McGeer, E. G. (1988) · Neurology · doi:10.1212/wnl.38.8.1285 · Cited by 2,990 · see citing works
Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo
Hickey, W. F., & Kimura, H. (1988) · Science · doi:10.1126/science.3276004 · Cited by 1,466 · see citing works
MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287 · cited 2× · see citing works
“Activated microglia and mediators (cytokines, complement factors and acute phase reactants) are indeed commonly found to be closely associated to degenerating neurons (McGeer and McGeer 1995).”
BackgroundVEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia
Sun, Y., Jin, K., Xie, L., Childs, J., Mao, X. O., Logvinova, A., & Greenberg, D. A. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317977 · Cited by 1,189 · see citing works
Turnover of resident microglia in the normal adult mouse brain
Lawson, L. J., Perry, V. H., & Gordon, S. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90500-2 · Cited by 709 · see citing works
Tomás-Camardiel, M., Rite, I., Herrera, A. J., de Pablos, R. M., Cano, J., Machado, A., & Venero, J. L. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.01.010 · Cited by 203 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Saraiva, C., Praça, C., Ferreira, R., Santos, T., Ferreira, L., & Bernardino, L. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.05.044 · Cited by 1,609 · see citing works
Neuroinflammation in Parkinson's disease and its potential as therapeutic target
Wang, Q., Liu, Y., & Zhou, J. (2015) · Translational Neurodegeneration · doi:10.1186/s40035-015-0042-0 · Cited by 884 · see citing works
Nanomaterial-based blood-brain-barrier (BBB) crossing strategies
Xie, J., Shen, Z., Anraku, Y., Kataoka, K., & Chen, X. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119491 · Cited by 604 · see citing works
Caspase signalling controls microglia activation and neurotoxicity
Burguillos, M. A., Deierborg, T., Kavanagh, E., Persson, A., Hajji, N., Garcia-Quintanilla, A., Cano, J., Brundin, P., Englund, E., Venero, J. L., et al. (2011) · Nature · doi:10.1038/nature09788 · Cited by 585 · see citing works
Self-citationNeurovascular signalling defects in neurodegeneration
Zacchigna, S., Lambrechts, D., & Carmeliet, P. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2336 · Cited by 345 · see citing works
Blood–brain barrier leakage is increased in parkinson’s disease
Al-Bachari, S., Naish, J. H., Parker, G. J. M., Emsley, H. C. A., & Parkes, L. M. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.593026 · Cited by 263 · 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
Andersen, H. H., Johnsen, K. B., & Moos, T. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1509-8 · Cited by 151 · see citing works
Desai Bradaric, B., Patel, A., Schneider, J. A., Carvey, P. M., & Hendey, B. (2012) · Journal of Neural Transmission · doi:10.1007/s00702-011-0684-8 · Cited by 139 · see citing works
Lan, G., Wang, P., Chan, R. B., Liu, Z., Yu, Z., Liu, X., Yang, Y., & Zhang, J. (2022) · Glia · doi:10.1002/glia.24109 · Cited by 122 · 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
Basal lamina changes in neurodegenerative disorders
Nguyen, B., Bix, G., & Yao, Y. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00502-y · Cited by 75 · see citing works
Between Dysbiosis, Maternal Immune Activation and Autism: Is There a Common Pathway?
Suprunowicz, M., Tomaszek, N., Urbaniak, A., Zackiewicz, K., Modzelewski, S., & Waszkiewicz, N. (2024) · Nutrients · doi:10.3390/nu16040549 · Cited by 44 · see citing works
- Authors
- Rite, I., Machado, A., Cano, J., & Venero, J. L.
- Affiliations
- Universidad de Sevilla (ES)
- ORCID
- Machado, Alberto
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-03-12
- Volume
- 101
- Issue
- 6
- Pages
- 1567-1582
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2002851005
- Cited by
- 147
- References
- 6
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 8 · 2019: 6 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 8 · 2014: 10 · 2013: 11 · 2012: 7
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Ciencia y Tecnología
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- blood-brain barrier disruption, Parkinson's disease, substantia nigra, dopaminergic neuron loss, vascular endothelial growth factor, blood-brain barrier permeability, tyrosine hydroxylase, neuronal apoptosis, caspase-3, astroglial activation, neuroinflammation, ventral mesencephalon
- MeSH terms
- Animals, Astrocytes, Blood-Brain Barrier, Dopamine, gamma-Aminobutyric Acid, Hippocampus, Male, Nerve Degeneration, Substantia Nigra, Tyrosine 3-Monooxygenase, Rats, Wistar, Apoptosis, Microglia, Vascular Endothelial Growth Factor A, Rats
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
