Comparison of the brain penetration injury associated with microdialysis and voltammetry
Open accessAbstract
Emerging evidence suggests that differences between microdialysis- and voltammetry-based estimates of extracellular dopamine in the brain might originate in the different penetration injury associated with each technique. To address this issue in a direct fashion, microdialysis probes and voltammetric microelectrodes were implanted in the rat striatum for 1, 4, or 24 h. Tissues were perfused with a suspension of fluorescently labeled nanobeads to assess blood vessels near the implant. Tissue sections (30 microm) were labeled with antibodies for PECAM, an endothelial cell marker, or GFAP, a glial marker. In non-implanted control tissue, blood vessels were reliably double-labeled with nanobeads and antiPECAM. Tissue near microdialysis probe tracks exhibited ischemia in the form of PECAM immunoreactive blood vessels devoid of nanobeads. Ischemia was most apparent after the 4-h implants. Probe tracks were surrounded by endothelial cell debris, which appeared as a diffuse halo of PECAM immunoreactivity. The halo intensity decreased with implant duration, indicative of an active wound-healing process. Consistent with this, after 24-h implants, the probe tracks were surrounded by hyperplasic and hypertrophic glia and glial processes were extending towards, and engulfing, the track. Carbon fiber microelectrodes produced a diffuse disruption of nanobead labeling but no focal disruption of blood vessels, no PECAM immunoreactive halo, and no glial activation. These findings illuminate the differences between the extent and nature of the penetration injuries associated with microdialysis and voltammetry.
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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 Jaquins-Gerstl and Michael, 2009
The Introduction (page unavailable) says penetration-injury severity and extent are related to penetrator size. The Discussion reports ischemic disruption around microdialysis probes but not comparable focal disruption around carbon-fiber microelectrodes. The paper does not establish the cited clause’s proposed mechanism—that larger implants exert more pressure and compress vessels. The hemorrhage-risk clause is cited to Rosidi et al., not to this paper. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSolutions for balancing power delivery and data transmission can result in compromises such as trade-offs between implant size and power capacity or between energy efficiency and data rate.
“However, these solutions can sometimes result in compromises, such as trade-offs between the size of the implant and its power capacity or between the energy efficiency and the data rate (Santiago and Westerink, 1990; Deboer and Abercrombie, 1996; Jaquins-Gerstl and Michael, 2009; Kozai et al., 2012).”
From Comparative analysis of energy transfer mechanisms for neural implants (2024) · cites this paper as Jaquins-Gerstl and Michael, 2009
The Introduction discusses how probe size relates to brain penetration injury, and the Discussion addresses changes in tissue after implantation. Neither addresses trade-offs between implant size and power capacity or between energy efficiency and data rate; searches for power delivery and data transmission found no relevant passage. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe inter-relationship between power transfer and data communication in neural implants introduces additional difficulty.
“Furthermore, the inter-relationship between power transfer and data communication in these implants introduces additional layers of difficulty.”
From Comparative analysis of energy transfer mechanisms for neural implants (2024) · cites this paper as Jaquins-Gerstl and Michael, 2009
The Discussion (page unavailable) compares tissue injury from microdialysis probes and carbon-fiber microelectrodes; the Voltammetry Procedures section (page unavailable) describes electrode operation. Neither addresses an inter-relationship between power transfer and data communication in neural implants. Searches for those terms and for wireless power, telemetry, and transmission found no relevant passage. (LLM, conf=0.76)
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“Furthermore, the microdialysis probes are quite large and implanted, they become encapsulated by a reactive glial scar [97].”
BackgroundComparative analysis of energy transfer mechanisms for neural implants
Miziev, S., Pawlak, W. A., & Howard, N. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1320441 · Cited by 21 · see citing works
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Varner, E. L., Leong, C. L., Jaquins‐Gerstl, A., Nesbitt, K. M., Boutelle, M. G., & Michael, A. C. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00148 · Cited by 24 · see citing works
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“Recent studies offer microdialysis probes with a high molecular weight cutoff membrane (16), modified membrane (17), or push pull perfusion systems (18–20) that bypass certain drawbacks associated with the traditional microdialysis probe, but most micro dialysis probes are still constrained by the following: (i) low…”
Background“Letting the little light of mind shine: Advances and future directions in neurochemical detection”
Tjahjono, N., Jin, Y., Hsu, A. C., Roukes, M., & Tian, L. (2021) · Neurosciences research · doi:10.1016/j.neures.2021.11.012 · Cited by 14
“Additionally, a large probe size increases tissue damage leading to ischemia, gliosis, and cell death at the insertion site (Jaquins-Gerstl and Michael, 2009).”
BackgroundLam, D., Javadekar, A., Patil, N. T., Yu, M. H., Li, L., Menendez, D. M., Gupta, A. S., Capadona, J. R., & Shoffstall, A. J. (2022) · SSRN Electronic Journal · doi:10.1016/j.actbio.2023.05.004 · Cited by 11 · see citing works
Wet-spun porous carbon microfibers for enhanced electrochemical detection
Ostertag, B. J., & Ross, A. E. (2023) · ACS Applied Materials and Interfaces · doi:10.1021/acsami.3c00423 · Cited by 13
Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models.
Hunsberger, H. C., Setti, S., Heslin, R. T., Quintero, J., Gerhardt, G., & Reed, M. N. (2017) · Journal of Visualized Experiments · doi:10.3791/55418 · Cited by 13
Marchoubeh, M. L., Cobb, S., Tello, M. A., Hu, M.-J., Jaquins-Gerstl, A., Robbins, E. M., Macpherson, J., Michael, A., & Fritsch, I. (2021) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-021-03327-2 · Cited by 12 · see citing works
“However, penetration injury surrounding a 7-μm diameter carbon fiber electrode is essentially non-detectable [44]), which allows carbon fiber electrodes to be placed in close proximity to dopamine terminals [10].”
BackgroundInfluentialSelf-citationVillarini, N. A., Robins, N., & Ou, Y. (2024) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c03093 · Cited by 13 · see citing works
Robbins, E. M., Jaquins‐Gerstl, A., Fine, D. F., Leong, C. L., Dixon, C. E., Wagner, A. K., Boutelle, M. G., & Michael, A. C. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00145 · Cited by 12 · see citing works
Self-citationTonic and Phasic Amperometric Monitoring of Dopamine Using Microelectrode Arrays in Rat Striatum
Lundblad, M., Price, D. A., Burmeister, J. J., Quintero, J. E., Huettl, P. F., Pomerleau, F., Zahniser, N. R., & Gerhardt, G. A. (2020) · Applied Sciences · doi:10.3390/app10186449 · Cited by 9 · see citing works
“Importantly, smaller sized electrochemical electrodes produce less tissue responsiveness and damage post-implantation in the brain [20,21].”
BackgroundInfluentialSchapira, I., O'Neill, M. R., Russo-Savage, L., Narla, T., Laprade, K. A., Stafford, J. M., & Ou, Y. (2023) · RSC Advances · doi:10.1039/d3ra04551j · Cited by 11 · see citing works
Physiologically Based Pharmacokinetic Model of Brain Delivery of Plasma Protein Bound Drugs
Pardridge, W. (2023) · Pharmaceutical Research · doi:10.1007/s11095-023-03484-2 · Cited by 7 · see citing works
Jaquins‐Gerstl, A., Nesbitt, K. M., & Michael, A. C. (2021) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-021-03300-z · Cited by 8 · see citing works
“Tissue fixation, processing, immunochemistry, and fluorescence microscopy followed our published procedures [33, 40, 41].”
MethodSelf-citationDexamethasone-Enhanced Microdialysis and Penetration Injury
Jaquins‐Gerstl, A., & Michael, A. C. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.602266 · Cited by 11 · see citing works
Self-citationMayer, S., Saxena, P., Crayen, M. A., & Treue, S. (2025) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2025.110361 · Cited by 4 · see citing works
Li, Y., Huang, Y., Chen, J. J., Hyland, B. I., & Wickens, J. R. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16269 · Cited by 5 · see citing works
“…analysis after the experiment was not undertaken because electrodes were removed immediately for calibration at the end of the experiment, and this type of carbon fiber electrode does not leave damage tracks (Jaquins-Gerstl & Michael, 2009, 2015; Mitch Taylor et al., 2012; Peters et al., 2004).”
MethodLow-Frequency Oscillations of In Vivo Ambient Extracellular Brain Serotonin
Witt, C. E., Mena, S., Honan, L. E., Batey, L., Salem, V., Ou, Y.-G., & Hashemi, P. (2022) · Cells · doi:10.3390/cells11101719 · Cited by 5 · see citing works
“Electrochemical methods have enabled faster, more localized serotonin measurements by using FSCV at CFMs, with negligible tissue damage [33,34].”
MethodAhn, S., & Phillips, A. (2013) · ACS Chemical Neuroscience · doi:10.1021/cn400040r · Cited by 5 · see citing works
Jaquins‐Gerstl, A., & Michael, A. C. (2013) · Neuromethods · doi:10.1007/978-1-62703-370-1_3 · Cited by 5 · see citing works
Self-citationAnalytical Applications of Membranes
Bruening, M. (2013) · doi:10.1002/9781118522318.emst122 · Cited by 4
Gifford, E. K., Robbins, E. M., Jaquins‐Gerstl, A., Rerick, M. T., Nwachuku, E. L., Weber, S. G., Boutelle, M. G., Okonkwo, D. O., Puccio, A. M., & Michael, A. C. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00231 · Cited by 5 · see citing works
Self-citationBinnetoğlu, D., Aricioglu, F., Özcan, H., Okkay, U., & Hacımüftüoğlu, A. (2019) · Clinical and Experimental Health Sciences · doi:10.33808/clinexphealthsci.613963 · Cited by 3 · see citing works
“Microdialysis, which is a very important method for the measurement of neurotransmitters, and if allowed to picomolar levels of substances in a sample to be analyzed in 20 minutes is a significant disadvantage (26).”
MethodApplication of Microdialysis for Pharmacokinetics of Traditional Chinese Medicine Studies
Cao, G., Cai, H., Cong, X.-D., Zhang, Y., Shao, Y., & Cai, B. (2009) · doi:10.1080/00032710903201958 · Cited by 3
“The small size of the dialysis probe, nominally 300 mm o.d. with an active window in the range 4–10mm in length, causes minimal perturbation to the tissue (Jaquins-Gerstl and Michael 2009).”
BackgroundColivicchi, M., Stefanini, C., Freinbichler, W., Ballini, C., Bianchi, L., Tipton, K., & della Corte, L. (2013) · Neuromethods · doi:10.1007/978-1-62703-173-8_11 · Cited by 3 · see citing works
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Mathematical Models of Serotonin, Histamine, and Depression
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“CFMEs have a small probe size (diameter 7 μm) and are biocompatible, creating minimal tissue damage and negligible immune response [48, 49].”
BackgroundChapter 19 Electrochemical Measurement of Neurochemical Concentrations
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“However, a very recent study showed that even at 24 hour post-implantation, signs of ischaemic disruption, though reduced compared to the first four hours, were still evident [341].”
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Effects of Anti-viral Acute Phase Response on Hippocampal Glutamate Regulation
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“The large sample 17 area (1-4mm in length) often causes damage and limits the detection of neuronal release (Borland, Shi, Yang, & Michael, 2005; Jaquins-Gerstl & Michael, 2009).”
Glutamate Dysregulation in a TauP301L Mouse Model of Alzheimer's Disease
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“Damage caused by the large sample area (1–4 mm in length) limited the detection of neuronal release (Borland, Shi, Yang, & Michael, 2005; Jaquins-Gerstl & Michael, 2009), and the low temporal resolution (1–20 min) was inadequate to measure the fast dynamics of glutamate uptake and clearance…”
BackgroundMicrodialysis Probe Requirements
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- Authors
- Jaquins-Gerstl, A., & Michael, A. C.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Michael, Adrian C.
- ORCID
- Michael, Adrian C.
- Venue
- Journal of Neuroscience Methods
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 183
- Issue
- 2
- Pages
- 127-135
- ISSN
- 0165-0270 (ISSN-L)
- PMC
- PMC2743756
- OpenAlex
- W2033922262
- Cited by
- 98
- References
- 60
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 11 · 2020: 4 · 2019: 7 · 2018: 3 · 2017: 7 · 2016: 6 · 2015: 2 · 2014: 9 · 2013: 12 · 2012: 8
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroscience Methods (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pittsburgh
- National Institutes of Health
- National Institute of Mental Health (#MH075989, R01MH075989)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Physical Sciences › Chemistry › Electrochemistry › Electrochemical Analysis and Applications
- Physical Sciences › Engineering › Electrical and Electronic Engineering › Electrochemical sensors and biosensors
- Keywords
- microdialysis, voltammetry, carbon fiber microelectrodes, extracellular dopamine, striatum, PECAM, glial activation, wound healing, implant duration
- MeSH terms
- Analysis of Variance, Animals, Blood Vessels, Brain Injuries, Corpus Striatum, Disease Models, Animal, Dopamine, Electric Stimulation, Electrodes, Implanted, Glial Fibrillary Acidic Protein, Male, Medial Forebrain Bundle, Time Factors, Wounds, Penetrating, Rats, Sprague-Dawley, Microdialysis, Platelet Endothelial Cell Adhesion Molecule-1, Rats, Electrochemical Techniques
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