Objective: Here we measured levels of vascular endothelial nitric oxide synthase (eNOS) expression as a result of high frequency (HF) Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) by analyzing STN vessels in Parkinson’s disease (PD) post-mortem brain tissue sections compared to neurological controls.

Background: STN-DBS is the favored surgical treatment for advanced PD. However, the mechanisms for the clinical benefits remain unclear. We recently revealed that STN-DBS modifies the microvessels in the stimulated STN (Pienaar et al. (2015). Neurobiol. Dis. 74:392-405), with upregulated vascular endothelial growth factor (VEGF) identified as a putative mechanism for the angiogenesis and neuroprotection seen in STN-DBS PD patients compared to non-DBS PD ones. VEGF improves cerebral blood flow through activation of the phosphoinositide 3-kinase-Akt pathway, which is known to regulate eNOS, which may have implications for neural plasticity (Son et al. (1996). Cell 87:1015-23).

Methods: Post-mortem STN-containing serial tissue sections were collected from neurological control and STN-DBS PD cases. We combined an eNOS-specific antibody stain with vascular endothelial cell staining (using glucose transporter (GLUT1) antibody). Stained sections were imaged as a z-stack of optical sections using laser-scanning confocal fluorescence microscopy. Maximum intensity projections and ImageJ software were used for fluorescence quantification with analysis restricted to the vascular endothelial cell layer. A distinction was made between macro- (venules and arterioles) and microvessels (capillaries), based upon lumen diameter.

Results: The endothelial cell layer of microvessels of stimulated PD cases showed enhanced eNOS expression (9,019 ± 3,441) compared to controls (7,822 ± 1,513), with similar results for macrovessels (9,510.44 ± 3,396, PD STN-DBS; 8,653 ± 2,596).

Conclusions: Nitrosative stress due to nitrogen species accumulation has been implicated in age-associated disorders. However, contrasting results showed a correlation between CNS plasticity and high nitrosative levels in the brain. The current data indicate that HF DBS may counter the vascular deficits seen in non-DBS PD reported in our earlier work, through upregulated eNOS produced in the vascular endothelial cells in the stimulated STN.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/upregulated-vascular-endothelial-nitric-oxide-synthase-in-parkinsons-disease-cases-that-have-received-subthalamic-stimulation-a-post-mortem-evaluation/