In vivo spatiotemporal dynamics of astrocyte reactivity following neural electrode implantation

Savya, Sajishnu P.; Li, Fan; Lam, Stephanie; Wellman, Steven M.; Stieger, Kevin C.; Chen, Keying; Eles, James R.; Kozai, Takashi D. Y.

doi:10.1016/j.biomaterials.2022.121784

Cited by 26 publications

(45 citation statements)

References 219 publications

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“…Astrocytes mediate the formation of a neurochemically impermeable and neurotoxic glial scar as part of the foreign body response to chronic brain implants. Previously, we presented a dynamic spatiotemporal pattern of astrocyte reactivity within the first few weeks during implantation using two-photon imaging around implanted microelectrodes 10 . Here, we demonstrate that astrocyte reactivity significantly increases from 1- to 16-weeks post-implantation in both WT and AD mice ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…WT and AD mice (6 and 18 m.o.) were implanted with a four-shank Michigan style microelectrode array for awake, head-fixed imaging, as described previously 5,8,10,[21][22][23] . Briefly, mice were sedated with an anesthetic cocktail (7 mg/kg xylazine and 75 mg/kg ketamine).…”

Section: Probe Implantation Surgerymentioning

confidence: 99%

“…Two-photon microscopy was used to track the rate of amyloid deposition or clearance around implanted microelectrodes in 6 month old WT and APP mice over a 16-week implantation period (0, 2, 4, 7, 14, 21, 28, 56, 84, and 112 days post-implantation), as described previously 8,10,21,22 . The microscope was equipped with a scan head (Bruker, Madison, WI), a OPO laser (Insight DS+; Spectra-Physics, Menlo Park, CA), non-descanned photomultiplier tubes (Hamamatsu Photonics KK, Hamamatsu, Shizuoka, Japan), and a 16X, 0.8 numerical aperture water-immersive objective lens (Nikon Instruments, Melville, NY).…”

Section: Two-photon Imaging and Aβ Labelingmentioning

confidence: 99%

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

Wellman

Coyne

Douglas

et al. 2023

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Probe Implantation Surgerymentioning

confidence: 99%

Section: Two-photon Imaging and Aβ Labelingmentioning

confidence: 99%

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

Wellman

Coyne

Douglas

et al. 2023

Preprint

Self Cite

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“…The disruption of gap junctions connecting oligodendrocytes and astrocytes has been shown to diminish the axonal firing [117], which highlight the importance of these gap junction in metabolite trafficking between oligodendrocyte to astrocytes. Following microelectrode implantation, astrocyte process migration occurs toward the probe within the first 7 days [118]. This activation may disrupt the oligodendrocyte-astrocyte gap junctions and result in fluctuation of firing activity (Fig.…”

Section: Oligodendrocyte Contribution To Energy Metabolismmentioning

confidence: 99%

“…1-4). Then, at chronic 2-4 weeks, astrocytes undergo hypertrophy and ultimately form an encapsulating glial scar [118], while oligodendrocytes and myelin progressively degenerate of near the microelectrode [59]. A disruption of oligodendrocyte-astrocyte coordination would lead to the dysfunction of metabolic support to neurons over the chronic implantation period, which could explain the overall loss of MCT1 (Fig.…”

Section: Oligodendrocyte Contribution To Energy Metabolismmentioning

confidence: 99%

Pro-myelinating Clemastine administration improves recording performance of chronically implanted microelectrodes and nearby neuronal health

Chen

Cambi

Kozai

2023

Preprint

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Intracortical microelectrodes have become a useful tool in neuroprosthetic applications in the clinic and to understand neurological disorders in basic neurosciences. Many of these brain-machine interface technology applications require successful long-term implantation with high stability and sensitivity. However, the intrinsic tissue reaction caused by implantation remains a major failure mechanism causing loss of recorded signal quality over time. Oligodendrocytes remain an underappreciated intervention target to improve chronic recording performance. These cells can accelerate action potential propagation and provides direct metabolic support for neuronal health and functionality. However, implantation injury causes oligodendrocyte degeneration and leads to progressive demyelination in surrounding brain tissue. Previous work highlighted that healthy oligodendrocytes are necessary for greater electrophysiological recording performance and the prevention of neuronal silencing around implanted microelectrodes over chronic implantation. Thus, we hypothesize that enhancing oligodendrocyte activity with a pharmaceutical drug, Clemastine, will prevent the chronic decline of microelectrode recording performance. Electrophysiological evaluation showed that the promyelination Clemastine treatment significantly elevated the signal detectability and quality, rescued the loss of multi-unit activity, and increased functional interlaminar connectivity over 16-weeks of implantation. Additionally, post-mortem immunohistochemistry showed that increased oligodendrocyte density and myelination coincided with increased survival of both excitatory and inhibitory neurons near the implant. Overall, we showed a positive relationship between enhanced oligodendrocyte activity and neuronal health and functionality near the chronically implanted microelectrode. This study shows that therapeutic strategy that enhance oligodendrocyte activity is effective for integrating the functional device interface with brain tissue over chronic implantation period.

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Flexible Neural Interface From Non‐Transient Silk Fibroin With Outstanding Conformality, Biocompatibility, and Bioelectric Conductivity

Hu,

Liang,

Fan

et al. 2024

Advanced Materials

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Silk fibroin (SF) with good biocompatibility can enable an efficient and safe implementation of neural interfaces. However, it has been difficult to achieve a robust integration of patterned conducting materials (multichannel electrodes) on flexible SF film substrates due to the absence of some enduring interactions. In this study, a thermo‐assisted pattern‐transfer technique is demonstrated that can facilely transfer a layer of pre‐set poly(3,4‐ethylenedioxythiophene) (PEDOT) onto the flexible SF substrate through an interpenetrating network of 2 polymer chains, achieving a desired substrate/conductor intertwined interface with good flexibility (≈33 MPa), conductivity (386 S cm−1) and stability in liquid state over 4 months simultaneously. Importantly, this technique can be combined with ink‐jet printing to prepare a multichannel SF‐based neural interface for the electrocorticogram (ECoG) recording and inflammation remission in rat models. The SF‐based neural interface with satisfied tissue conformability, biocompatibility, and bioelectric conductivity is a promising ECoG acquisition tool, where the demonstrated approach can also be useful to develop other SF‐based flexible bioelectronics.

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In vivo spatiotemporal dynamics of astrocyte reactivity following neural electrode implantation

Cited by 26 publications

References 219 publications

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

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

Pro-myelinating Clemastine administration improves recording performance of chronically implanted microelectrodes and nearby neuronal health

Flexible Neural Interface From Non‐Transient Silk Fibroin With Outstanding Conformality, Biocompatibility, and Bioelectric Conductivity

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