De-coupling the Neurovascular Unit at the Electrode-Tissue Interface

Steven Wellman
Graduate Research Assistant
Department of Bioengineering
University of Pittsburgh

Abstract:  The success of neural interface technology to understand brain function and restore lost motor or sensory control is dependent on reliable and robust recordings of neuronal activity. However, the ability to detect extracellular potentials in the brain using intracortical microelectrodes is impeded by a seemingly insurmountable foreign body reaction. Attempts at identifying potential biological correlates to device performance are obscured by a high variability in tissue response outcomes. This variability may be attributed to currently unknown consequences of different glial and vascular components that are intimately involved within the brain’s neurovascular unit (NVU). The primary function of the NVU is to mediate delivery of oxygen and nutrients required to meet the energetic demands of neurons and other active brain cells as well as expel accrued metabolic waste. As a result, neuronal activity and neurovascular function are intimately linked, and NVU dysfunction is increasingly associated with neurodegenerative outcomes. Using a combination of in vivo multiphoton imaging, electrophysiology, and immunohistology, I will reveal structural and functional alterations of relatively understudied cells observed within the electrode-tissue interface, such as oligodendrocytes and vascular pericytes. Towards the end of my talk, I will briefly discuss some emerging work from our group investigating the accumulation of age-related proteins and disease-related pathology around penetrating brain implants. Future research highlighting the fate and significance of these critical cellular and tissue components during brain injury and disease will help guide more innovative device designs and strategies to improve electrode-tissue integration, chronic electrode stability, and long-term functional device performance.

Bio:  Steven earned his bachelor’s in Biomedical Engineering from the University of Florida (UF). At UF, Steven optimized chemical-free decellularization protocols to preserve the structure of acellularized nerve scaffolds for functional recovery of peripheral nerve injuries within Dr. Christine Schmidt’s lab. Shifting his research interests towards understanding brain health and disease, Steven joined Dr. Takashi Kozai’s lab at Pitt as a doctoral student exploring how implantable neural electrodes alter the structure and function of myelinating oligodendrocytes and perivascular pericytes within the brain using a combination of in vivo two-photon microscopy, electrophysiology, and immunohistology techniques. While at Pitt, Steven has earned a NIH diversity supplement from NINDS, a departmental travel grant award, and received distinction as Outstanding Research Assistant by the local graduate chapter of the Biomedical Engineering Society (BMES). Steven is currently acting as an NIH F99/K00 fellow whose long-term goal is to apply advanced neurotechnology to understand and treat neurodegenerative brain diseases, such as Alzheimer’s disease, while fostering an inclusive academic research environment that inspires and elevates the next generation of neuroscientists, particularly those from historically underrepresented backgrounds.