Deep-brain stimulation associates with improved microvascular integrity in the subthalamic nucleus in Parkinson's disease

NEUROBIOLOGY OF DISEASE

卷:74

Article

Pienaar, Ilse S.¹  Lee, Cecilia Heyne²  Elson, Joanna L.^3,4  McGuinness, Louisa¹  Gentleman, Stephen M.¹  Kalaria, Raj N.⁵  Dexter, David T.¹ 

[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Brain Sci, Ctr Neuroinflammat & Neurodegenerat, London W12 0NN, England

[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[3] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[4] North West Univ, Ctr Human Metabon, Potchefstroom, South Africa

[5] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England

关键词: Deep-brain stimulation;    Growth factor;    Parkinson's disease;    Subthalamic nucleus;    Tight junction proteins;    Vasculature;   

DOI  :  10.1016/j.nbd.2014.12.006

来源: Elsevier

【 摘 要 】

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 (VEGF), was significantly upregulated compared to the other groups. Our findings suggest that overexpressed VEGF and downregulation of inflammatory processes may be critical mechanisms underlying the DBS-induced microvascular changes. (C) 2014 Elsevier Inc. All rights reserved.

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