Post-mortem analysis of parkinson’s disease brains after long-term deep brain stimulation of the subthalamic nucleus

Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective surgical treatment for Parkinson’s disease (PD), alleviating motor symptoms and restoring patients’ quality of life. Research into the long-term effects of DBS on the human brain is lacking. This study aims to investigate the neuroanatomical and neurochemical alterations induced by chronic stimulations of the STN, and to correlate these changes with clinical outcomes and estimated electrical current delivered in the brain parenchyma. Brains of PD patients who had received more than 9 years of DBS treatment in the STN were used. For each brain, 3D graphical representations of the basal ganglia and DBS electrodes were produced to determine the electrical current propagation throughout the tissue using patient-specific DBS computational modelling (StimVision2). Immunofluorescence and confocal microscopy were used to determine the immunoreactivity of various proteins. Quantification and morphological analyses of different cell types and blood vessels were performed. Along the electrode path, a 300-500 μm-width GFAP positive fibrillary gliosis was observed, with elevated expression of the growth factor GDNF. Near active contacts, astrocytes showed higher number of varicose processes that were in close apposition to GLUT1+ blood vessels. The number of Iba1+ microglia as well as the CD68 phagocytic marker was reduced and there were increased levels of VEGF and Claudin5 on GLUT1+ blood vessels, suggesting angiogenesis and increased blood brain barrier integrity. A detailed morphological analysis of microglia indicates that they were more active in the stimulated area of the STN. Overall, our post-mortem analysis indicates significant changes induced by long-term DBS of the STN involving glial cells and blood-brain barrier. Research Category and Technology and Methods Basic Research: 1. Deep Brain Stimulation (DBS) Keywords: basal ganglia, neurodegenerative disorders, DBS, neuroplasticity