Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Dec 22:11:593026.
doi: 10.3389/fphys.2020.593026. eCollection 2020.

Blood-Brain Barrier Leakage Is Increased in Parkinson's Disease

Sarah Al-Bachari  1   2   3 , Josephine H Naish  4   5 , Geoff J M Parker  5   6 , Hedley C A Emsley  1   2   3 , Laura M Parkes  3   7
Affiliations

Blood-Brain Barrier Leakage Is Increased in Parkinson's Disease

Sarah Al-Bachari et al. Front Physiol. .

Abstract

Background: Blood-brain barrier (BBB) disruption has been noted in animal models of Parkinson's disease (PD) and forms the basis of the vascular hypothesis of neurodegeneration, yet clinical studies are lacking.

Objective: To determine alterations in BBB integrity in PD, with comparison to cerebrovascular disease.

Methods: Dynamic contrast enhanced magnetic resonance images were collected from 49 PD patients, 15 control subjects with cerebrovascular disease [control positive (CP)] and 31 healthy control subjects [control negative (CN)], with all groups matched for age. Quantitative maps of the contrast agent transfer coefficient across the BBB (K trans) and plasma volume (v p ) were produced using Patlak analysis. Differences in K trans and v p were assessed with voxel-based analysis as well as in regions associated with PD pathophysiology. In addition, the volume of white matter lesions (WMLs) was obtained from T2-weighted fluid attenuation inversion recovery (FLAIR) images.

Results: Higher K trans, reflecting higher BBB leakage, was found in the PD group than in the CN group using voxel-based analysis; differences were most prominent in the posterior white matter regions. Region of interest analysis confirmed K trans to be significantly higher in PD than in CN, predominantly driven by differences in the substantia nigra, normal-appearing white matter, WML and the posterior cortex. WML volume was significantly higher in PD compared to CN. K trans values and WML volume were similar in PD and CP, suggesting a similar burden of cerebrovascular disease despite lower cardiovascular risk factors.

Conclusion: These results show BBB disruption in PD.

Keywords: Parkinson’s disease; blood–brain barrier; cerebrovascular disease; dynamic contrast enhanced MRI; neurovascular unit.

PubMed Disclaimer

Conflict of interest statement

Authors JN and GP were part employed by the company Bioxydyn and hold shares in the company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Location of the regions of interest.
FIGURE 2
FIGURE 2
Mean images of Ktrans and vp for each group. Images of the mean contrast agent transfer coefficient Ktrans and the plasma volume vp for each group. Individual images were first normalised to MNI space before averaging. A T1-weighted image is shown for reference.
FIGURE 3
FIGURE 3
Regions of higher Ktrans in the PD group compared to the CN group. t-statistic map overlaid on structural image showing the regions of significantly higher Ktrans in the PD group than in the CN group. Map is thresholded with voxel-level p < 0.001 (uncorrected) and minimum cluster size of 50 voxels. The arrow indicates the cluster that survives cluster-level family wise error correction for multiple comparisons (p < 0.05).
FIGURE 4
FIGURE 4
Mean values for Ktrans and vp in regions of interest for each group. Mean values are given for (A) the contrast agent transfer coefficient Ktrans and (B) the plasma volume vp. Error bars show the standard error in the mean. The significance of post hoc t-tests (uncorrected) between Ktrans in the PD and CN group are shown. SN, substantia nigra; CA, caudate; PU, putamen; P, pallidum; WMLs, white matter lesions; NAWM, normal-appearing white matter; FC, frontal cortex; PC, posterior cortices.
See this image and copyright information in PMC

References

    1. Al-Bachari S., Vidyasagar R., Emsley H. C., Parkes L. M. (2017). Structural and physiological neurovascular changes in idiopathic Parkinson’s disease and its clinical phenotypes. J. Cereb. Blood Flow Metab. 37 3409–3421. 10.1177/0271678x16688919 - DOI - PMC - PubMed
    1. Alvarez J. I., Katayama T., Prat A. (2013). Glial influence on the blood brain barrier. Glia 61 1939–1958. 10.1002/glia.22575 - DOI - PMC - PubMed
    1. Andreone B. J., Lacoste B., Gu C. (2015). Neuronal and vascular interactions. Annu. Rev. Neurosci. 38 25–46. 10.1146/annurev-neuro-071714-033835 - DOI - PMC - PubMed
    1. Barcia C., Bautista V., Sanchez-Bahillo A., Fernandez-Villalba E., Faucheux B., Poza y Poza M., et al. (2005). Changes in vascularization in substantia nigra pars compacta of monkeys rendered parkinsonian. J. Neural Transm. 112 1237–1248. 10.1007/s00702-004-0256-2 - DOI - PubMed
    1. Bell R. D., Winkler E. A., Sagare A. P., Singh I., LaRue B., Deane R., et al. (2010). Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 68 409–427. 10.1016/j.neuron.2010.09.043 - DOI - PMC - PubMed