In vivo spatiotemporal dynamics of astrocyte reactivity following neural electrode implantation

Abstract

Brain computer interfaces (BCIs), including penetrating microelectrode arrays, enable both recording and stimulation of neuronal cells. However, device implantation inevitably causes injury to brain tissue and induces a foreign body response, leading to reduced recording performance and stimulation efficacy. Astrocytes in the healthy brain play multiple roles including regulating energy metabolism, homeostatic balance, transmission of neural signals, and neurovascular coupling. Following an insult to the brain, they are activated and observed to gather around the site of injury. These reactive astrocytes have been regarded as one of the main contributors to the formation of a glial scar which affects the performance of microelectrode arrays. This study investigates the dynamics of astrocytes within the first 2 weeks after implantation of an intracortical microelectrode into the mouse brain using two-photon microscopy. From our observation astrocytes are highly dynamic during this period, exhibiting patterns of process extension, soma migration, morphological activation, and device encapsulation that are spatiotemporally distinct from other glial cells, such as microglia or oligodendrocyte precursor cells. This detailed characterization of astrocyte reactivity will help to better understand the tissue response to intracortical devices and lead to the development of more effective intervention strategies to improve the functional performance neural interfacing technology.

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

“…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.…”

“…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.…”

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

“…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).…”

“…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).…”

“…This acute insult leads to the activation of local glial and immune cells and release of factors which promotes inflammation, excitotoxicity, and oxidative stress, compromising local metabolic support 4 . The long-term presence of an indwelling electrode inevitably results in the development of an encapsulating glial scar impermeable to the diffusion of ions and metabolites required to detect neuronal activity, which can physically displace neurons farther from the device surface and produce a neurotoxic microenvironment 5,10 . The gradual decline in performance and fidelity of recording and stimulating electrodes is ultimately attributed to this seemingly unavoidable progression in gliosis and neurodegeneration 11 .…”