In vivo two-photon microscopy reveals immediate microglial reaction to implantation of microelectrode through extension of processes

Kozai, Takashi D Yoshida; Vazquez, Alberto L; Weaver, Cassandra L; Kim, Seong-Gi; Cui, X Tracy

doi:10.1088/1741-2560/9/6/066001

Cited by 215Neuroscience and Neural EngineeringNeuroinflammation and Neurodegeneration MechanismsTraumatic Brain Injury and Neurovascular Disturbances

In vivo two-photon microscopy reveals immediate microglial reaction to implantation of microelectrode through extension of processes

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Kozai, Takashi D Yoshida, Vazquez, Alberto L, Weaver, Cassandra L, Kim, Seong-Gi, Cui, X Tracy·2012·Journal of Neural Engineering

DOI 10.1088/1741-2560/9/6/066001PMC PMC3511663

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Abstract

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.
“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
Kozai et al. is cited for the sentence’s second clause, not the size–risk correlation attributed to Rosidi et al. In the Discussion sections on acute BBB microhemorrhage and mechanical strain (page unavailable), the paper links probe volume to tissue displacement and damage, and reports nearby capillaries losing perfusion. It does not establish that larger implants exert more pressure or that their size causes vascular compression and secondary injuries. (LLM, conf=0.84)
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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
ORCID: Kozai, Takashi D Yoshida
Vazquez, Alberto L
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
DOI: 10.1088/1741-2560/9/6/066001
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 › 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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In vivo two-photon microscopy reveals immediate microglial reaction to implantation of microelectrode through extension of processes

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