LIPUS

Our work involves creating ischemic environments through microelectrode implantation to study glial dysregulation and neuronal silencing. We investigate how these conditions affect metabolic stress and neuronal activity, particularly in Alzheimer's Disease (AD) and Multiple Sclerosis (MS), using electrophysiological techniques. To further understand the interactions between glial cells, vasculature, and ischemic events, we utilize advanced imaging methods, such as in vivo two-photon microscopy, to observe and analyze the behavior of various cell types—including neurons, microglia, astrocytes, oligodendrocytes, oligodendrocyte precursor cells, pericytes, and endothelial cells—and their interactions with the cerebral vasculature.Additionally, we explore the therapeutic potential of electrical and ultrasound stimulation to modulate neuronal and non-neuronal cells, aiming to enhance brain repair mechanisms and improve overall brain health. Our prior research demonstrated that ultrasound stimulation can modulate the immune response to microelectrode implantation. We are now poised to assess the potential therapeutic mechanisms of ultrasound stimulation specifically in the context of brain diseases such as Alzheimer's Disease.Our collaboration with Actuated Medical, Inc. will advance the development of a noninvasive low-intensity pulsed ultrasound (LIPUS) system designed to reduce neuroinflammatory cytokines derived from microglia. This SBIR project will enable us to establish the feasibility of this approach in rodent models, with the long-term goal of scaling up to primate models and ultimately developing a clinical device for patient use.The research environment at Actuated Medical, Inc., combined with my extensive background in ultrasound technologies and in vivo imaging methods, provides a robust platform for producing impactful research outcomes. I will lead this project, ensuring meticulous execution of experiments, accurate interpretation of data, and effective training for all team members.Key Publications:
  • Li F, Gallego J, Tirko NN, Greaser J, Bashe D, Patel R, Shaker E, Van Valkenburg GE, Alsubhi AS, Wellman W, Singh V, Garcia Padilla C, Gheres KW, Broussard JI, Bagwell R, Mulvihill M, Kozai TDY. Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation. Nature Communications. 2024. 15, 5512.
  • Chen K, Garcia C, Kiselyov K, Kozai TDY. Cell-specific alterations in autophagy-lysosomal activity near chronically implanted microelectrodes. Biomaterials. 2023. 302, 122316.
  • Wellman SM, Coyne OA, Douglas MM, Kozai TDY. Aberrant accumulation of age- and disease-associated factors following neural probe implantation in a mouse model of Alzheimer’s disease. Journal of Neural Engineering. 2023. 20, 046044.
  • Fitz N, Nam KN, Wolfe C, Letronne F, Playso B, Iordanova B, Kozai TDY, Biedrzycki, Tyurina Y, Han X, Lefterov I, Koldamova R. Phospholipid Composition of APOE Lipoproteins Affects Microglia Activation in an Isoform-specific Manner. Nature Communications. 2021. 12(1), 1-18.