Aberrant accumulation of age- and disease-associated factors following neural probe implantation in a mouse model of Alzheimer’s disease

Abstract

Electrical stimulation has had a profound impact on our current understanding of nervous system physiology and provided viable clinical options for addressing neurological dysfunction within the brain. Unfortunately, the brains immune suppression of indwelling microelectrodes currently presents a major roadblock in the long-term application of neural recording and stimulating devices. In some ways, brain trauma induced by penetrating microelectrodes produces similar neuropathology as debilitating brain diseases, such as Alzheimers disease (AD), while also suffering from end-stage neuron loss and tissue degeneration. To understand whether there may be any parallel mechanisms at play between brain injury from chronic microelectrode implantation and those of neurodegenerative disorder, we used two-photon microscopy to visualize the accumulation, if any, of age- and disease-associated factors around chronically implanted electrodes in both young and aged mouse models of AD. With this approach, we determined that electrode injury leads to aberrant accumulation of lipofuscin, an age-related pigment, in wild-type and AD mice alike. Furthermore, we reveal that chronic microelectrode implantation reduces the growth of pre-existing amyloid plaques while simultaneously elevating amyloid burden at the electrode-tissue interface. Lastly, we uncover novel spatial and temporal patterns of glial reactivity, axonal and myelin pathology, and neurodegeneration related to neurodegenerative disease around chronically implanted microelectrodes. This study offers multiple novel perspectives on the possible neurodegenerative mechanisms afflicting chronic brain implants, spurring new potential avenues of neuroscience investigation and design of more targeted therapies for improving neural device biocompatibility and treatment of degenerative brain disease.

Impact of electrodes design and insertion methods to surrounding cortical tissues from high-density arrays

“…Two-photon microscopy techniques were used to examine the cellular responses to tip profile under in vivo conditions in mice and followed the similar procedures in previous work 64,[66][67][68][71][72][73][74][75][76][77] . The microscope for the in vivo imaging used a scan head (Ultima I.V.…”