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

• DOI: 10.1016/j.brs.2023.03.017
• Publication Date: 2023-05-04T20:42:01Z
• Authors: Jonathan Munro; Francis Desmeules; Sylvine Cottin Ca...; Angela Noecker; Marie-Ève Tremblay; Peter V. Gould; Stephan Saikali; Mélanie Langlois; Michel Prud’homme; Cameron C. McIntyre; Léo Cantin; Parent Martin
• Keywords: Subthalamic Nucleus; Gliosis

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