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In vivo two-photon microscopy reveals immediate microglial reaction to implantation of microelectrode through extension of processes
Open accessAbstract
OBJECTIVE: Penetrating cortical neural probe technologies allow investigators to record electrical signals in the brain. Implantation of probes results in acute tissue damage, and microglia density increases around implanted devices over weeks. However, the mechanisms underlying this encapsulation are not well understood in the acute temporal domain. The objective here was to evaluate dynamic microglial response to implanted probes using two-photon microscopy. APPROACH: Using two-photon in vivo microscopy, cortical microglia ∼200 µm below the surface of the visual cortex were imaged every minute in mice with green fluorescent protein-expressing microglia. MAIN RESULTS: Following probe insertion, nearby microglia immediately extended processes toward the probe at (1.6 ± 1.3) µm min(-1) during the first 30-45 min, but showed negligible cell body movement for the first 6 h. Six hours following probe insertion, microglia at distances <130.0 µm (p = 0.5) from the probe surface exhibit morphological characteristics of transitional stage (T-stage) activation, similar to the microglial response observed with laser-induced blood-brain barrier damage. T-stage morphology and microglia directionality indexes were developed to characterize microglial response to implanted probes. Evidence suggesting vascular reorganization after probe insertion and distant vessel damage was also observed hours after probe insertion. SIGNIFICANCE: A precise temporal understanding of the cellular response to microelectrode implantation will facilitate the search for molecular cues initiating and attenuating the reactive tissue response.
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“The implant’s size and volume directly correlate with the risk of intracerebral hemorrhage and ischemic injuries (Rosidi et al., 2011), with larger implants exerting more pressure, potentially leading to vascular compression and secondary injuries (Jaquins-Gerstl and Michael, 2009; Kozai et al., 2012).”
From Comparative analysis of energy transfer mechanisms for neural implants (2024) · cites this paper as Kozai et al., 2012
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Metadata
- Authors
- Kozai, T. D. Y., Vazquez, A. L., Weaver, C. L., Kim, S.-G., & Cui, X. T.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Kozai, Takashi D Yoshida
- Cui, X Tracy
- Venue
- Journal of Neural Engineering
- Publisher
- IOP Publishing
- Published
- 2012-10-17
- Volume
- 9
- Issue
- 6
- Pages
- 066001
- ISSN
- 1741-2552 (ISSN-L)
- 1741-2560
- PMC
- PMC3511663
- OpenAlex
- W2050826469
- Cited by
- 215
- References
- 85
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 20 · 2023: 21 · 2022: 16 · 2021: 19 · 2020: 19 · 2019: 15 · 2018: 16 · 2017: 17 · 2016: 15 · 2015: 15 · 2014: 12 · 2013: 3 · 2012: 1
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neural Engineering (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (5R01NS44589, R01NS044589, R01NS062019, K01NS066131)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- microglia, microglial activation, visual cortex, two-photon microscopy, neuroprosthetics
- MeSH terms
- Algorithms, Animals, Blood-Brain Barrier, Brain, Craniotomy, Data Interpretation, Statistical, Electrodes, Implanted, Image Processing, Computer-Assisted, Mice, Transgenic, Microelectrodes, Microscopy, Visual Cortex, Microglia, Photons, Green Fluorescent Proteins, Mice
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