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

Lookup NU author(s): Dr Ilse Pienaar, Dr Joanna Elson, Professor Raj Kalaria

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Abstract

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.


Publication metadata

Author(s): Pienaar IS, Lee CH, Elson JL, McGuinness L, Gentleman SM, Kalaria RN, Dexter DT

Publication type: Article

Publication status: Published

Journal: Neurobiology of Disease

Year: 2015

Volume: 74

Pages: 392–405

Print publication date: 01/02/2015

Online publication date: 19/12/2014

Acceptance date: 05/12/2014

ISSN (print): 0969-9961

ISSN (electronic): 1095-953X

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.nbd.2014.12.006

DOI: 10.1016/j.nbd.2014.12.006

PubMed id: 25533682


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