Deep-brain stimulation associates with improved microvascular integrity in the subthalamic nucleus in Parkinson's disease
Open accessAbstract
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an accepted treatment for motor symptoms in a subset of Parkinson's disease (PD) patients. The mechanisms why DBS is effective are incompletely understood, but previous studies show that DBS targeted in brain structures other than the STN may modify the microvasculature. However, this has not been studied in PD subjects who have received STN-DBS. Here we investigated the extent and nature of microvascular changes in post-mortem STN samples from STN-DBS PD patients, compared to aged controls and PD patients who had not been treated with STN-DBS. We used immunohistochemical and immunofluorescent methods to assess serial STN-containing brain sections from PD and STN-DBS PD cases, compared to similar age controls using specific antibodies to detect capillaries, an adherens junction and tight junction-associated proteins as well as activated microglia. Cellular features in stained sections were quantified by confocal fluorescence microscopy and stereological methods in conjunction with in vitro imaging tools. We found significant upregulation of microvessel endothelial cell thickness, length and density but lowered activated microglia density and striking upregulation of all analysed adherens junction and tight junction-associated proteins in STN-DBS PD patients compared to non-DBS PD patients and controls. Moreover, in STN-DBS PD samples, expression of an angiogenic factor, vascular endothelial growth factor…
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Deep brain stimulation effectiveness in improving Parkinson's disease motor symptoms is credited to microvascular improvements.
“Deep brain stimulation (DBS) is commonly used to improve PD-related motor symptoms, and its effectiveness is credited to microvascular improvements (250, 473).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [473]
In Parkinson's disease, there is substantial loss of endothelial cells in the basal ganglia, reduced levels of tight junction proteins, and alteration of capillary basement membrane.
“In the PD, there is a substantial loss of endothelial cells in the basal ganglia, reduced levels of TJ proteins, and alteration of capillary basement membrane (473).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [473]
In Parkinson's disease patients, histological analysis reveals blood-brain barrier breakdown in the striatum shown by capillary leakages, perivascular fibrin(ogen) and IgG deposits, hemosiderin, and RBC extravasation.
“Throughout the basal ganglia, histological analysis of PD patients reveals BBB breakdown in the striatum as shown by capillary leakages and accumulation of perivascular fibrin(ogen) (214) and IgG (473) deposits, hemosiderin (214, 373), and RBCs extravasation (214).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [473]
Parkinson's disease patients who underwent deep brain stimulation exhibit increased capillary length and density, increased tight junction and adherens junction protein expression, and reduced perivascular IgG leakage at post mortem tissue analysis.
“PD patients that underwent DBS exhibit increased capillary length and density, increased TJ and AJ protein expression, and reduced perivascular IgG leakage at post mortem tissue analysis (473).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [473]
Cites
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
Neuroglial activation and neuroinflammation in the brain of patients with autism
Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005) · Annals of Neurology · doi:10.1002/ana.20315 · Cited by 2,149 · see citing works
Size-selective loosening of the blood-brain barrier in claudin-5–deficient mice
Nitta, T., Hata, M., Gotoh, S., Seo, Y., Sasaki, H., Hashimoto, N., Furuse, M., & Tsukita, S. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200302070 · Cited by 1,917 · see citing works
Microglia: activation and their significance in the central nervous system
Nakajima, K., & Kohsaka, S. (2001) · Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a002969 · Cited by 371 · see citing works
Cerebral Angiogenesis and Expression of Angiogenic Factors in Aging Rats after Exercise
Ding, Y.-H., Li, J., Zhou, Y., Rafols, J., Clark, J., & Ding, Y. (2006) · Current Neurovascular Research · doi:10.2174/156720206775541787 · Cited by 223 · see citing works
Rosenstein, J. M., Mani, N., Khaibullina, A., & Krum, J. M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-35-11036.2003 · Cited by 220 · 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
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Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076 · 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
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Knox, E. G., Aburto, M. R., Clarke, G., Cryan, J. F., & O’Driscoll, C. M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01511-z · Cited by 738 · see citing works
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Zha, S., Liu, H., Li, H., Li, H., Wong, K.-L., & All, A. H. (2024) · ACS Nano · doi:10.1021/acsnano.3c10674 · Cited by 378 · see citing works
Glycosphingolipids and Neuroinflammation in Parkinson’s Disease
Belarbi, K., Cuvelier, E., Bonte, M.-A., Desplanque, M., Gressier, B., Devos, D., & Chartier-Harlin, M.-C. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00408-1 · Cited by 155 · 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
- Authors
- Pienaar, I. S., Lee, C. H., Elson, J. L., McGuinness, L., Gentleman, S. M., Kalaria, R. N., & Dexter, D. T.
- Affiliations
- Hammersmith Hospital (GB)
- University of Oxford (GB)
- North-West University (ZA)
- Newcastle University (GB)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 74
- Pages
- 392-405
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2136193649
- Cited by
- 125
- References
- 7
- Citations by year
- 2026: 6 · 2025: 20 · 2024: 15 · 2023: 14 · 2022: 10 · 2021: 9 · 2020: 16 · 2019: 10 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 9
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Northumbria Research Link (Northumbria University) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- UK Parkinson's Disease Society
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- deep brain stimulation, subthalamic nucleus, Parkinson's disease, microvascular integrity, capillary density, adherens junction proteins, tight junction proteins, activated microglia, vascular endothelial growth factor, angiogenesis, neuroinflammation, postmortem brain
- MeSH terms
- Aged, Aged, 80 and over, Female, Fluorescent Antibody Technique, Humans, Immunoglobulin G, Immunohistochemistry, Male, Organ Size, Parkinson Disease, Treatment Outcome, Microglia, Subthalamic Nucleus, Vascular Endothelial Growth Factor A, Endothelial Cells, Deep Brain Stimulation, Glucose Transporter Type 1, Microvessels, Tight Junction Proteins
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