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