The surface immobilization of the neural adhesion molecule L1 on neural probes and its effect on neuronal density and gliosis at the probe/tissue interface
Open accessAbstract
Brain tissue inflammatory responses, including neuronal loss and gliosis at the neural electrode/tissue interface, limit the recording stability and longevity of neural probes. The neural adhesion molecule L1 specifically promotes neurite outgrowth and neuronal survival. In this study, we covalently immobilized L1 on the surface of silicon-based neural probes and compared the tissue response between L1 modified and non-modified probes implanted in the rat cortex after 1, 4, and 8 weeks. The effect of L1 on neuronal health and survival, and glial cell reactions were evaluated with immunohistochemistry and quantitative image analysis. Similar to previous findings, persistent glial activation and significant decreases of neuronal and axonal densities were found at the vicinity of the non-modified probes. In contrast, the immediate area (100 μm) around the L1 modified probe showed no loss of neuronal bodies and a significantly increased axonal density relative to background. In this same region, immunohistochemistry analyses show a significantly lower activation of microglia and reaction of astrocytes around the L1 modified probes when compared to the control probes. These improvements in tissue reaction induced by the L1 coating are likely to lead to improved functionality of the implanted neural electrodes during chronic recordings.
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Azemi et al. reported a pronounced improvement in neurofilament staining within the first 100 mm of the probe surface over the entire 8-week study period.
“Azemi et al. reported a pronounced improvement in neuronal density and neurofilament staining within the first 100 mm of the probe surface over the entire 8-week study period.77”
From Regenerative Electrode Interfaces for Neural Prostheses. (2016) · cites this paper as [77]
Results §3.1 reports greater NF-200 staining around L1-modified probes than controls within 100 μm of the interface at all three time points (1, 4, and 8 weeks). It also reports higher neuronal cell counts in that region. The citing sentence says 100 mm, which is not the distance reported by the source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAzemi et al. reported a pronounced improvement in neuronal density within the first 100 mm of the probe surface over the entire 8-week study period.
“Azemi et al. reported a pronounced improvement in neuronal density and neurofilament staining within the first 100 mm of the probe surface over the entire 8-week study period.77”
From Regenerative Electrode Interfaces for Neural Prostheses. (2016) · cites this paper as [77]
Results §3.1 reports significantly higher neuronal counts and NF-200 staining around L1-modified probes than controls at 1, 4, and 8 weeks. The reported region is within 100 μm of the interface, not 100 mm as printed in the citing sentence; page numbers were not provided. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCoating electrodes with L1 reduced gliosis surrounding devices implanted in rat motor cortex.
“Likewise, coating electrodes with L1 reduced gliosis and improved neuronal density surrounding devices implanted in rat motor cortex.77”
From Regenerative Electrode Interfaces for Neural Prostheses. (2016) · cites this paper as [77]
While typical neuronal loss occurred at the device interface surrounding control implants, no such reduction in neuronal density was evident surrounding L1-coated implants.
“Remarkably, while there was evidence of typical neuronal loss at the device interface surrounding control implants, no such reduction in neuronal density was evident surrounding L1-coated implants.”
From Regenerative Electrode Interfaces for Neural Prostheses. (2016) · cites this paper as [77]
Coating electrodes with L1 improved neuronal density surrounding devices implanted in rat motor cortex.
“Likewise, coating electrodes with L1 reduced gliosis and improved neuronal density surrounding devices implanted in rat motor cortex.77”
From Regenerative Electrode Interfaces for Neural Prostheses. (2016) · cites this paper as [77]
L1 is expressed in the majority of CNS neurons.
“L1 contributes many essential functions to the maintenance of the nervous system, where it is expressed in the majority of CNS neurons and has reported neuroprotective effects.77”
From Regenerative Electrode Interfaces for Neural Prostheses. (2016) · cites this paper as [77]
L1 has reported neuroprotective effects.
“L1 contributes many essential functions to the maintenance of the nervous system, where it is expressed in the majority of CNS neurons and has reported neuroprotective effects.77”
From Regenerative Electrode Interfaces for Neural Prostheses. (2016) · cites this paper as [77]
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References 51 · Cited by 164
- Authors
- Azemi, E., Lagenaur, C. F., & Cui, X. T.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Cui, Xinyan T.
- ORCID
- Cui, Xinyan T.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 32
- Issue
- 3
- Pages
- 681-692
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3394228
- OpenAlex
- W2001702704
- Cited by
- 164
- References
- 51
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 6 · 2023: 13 · 2022: 8 · 2021: 12 · 2020: 13 · 2019: 7 · 2018: 10 · 2017: 13 · 2016: 9 · 2015: 11 · 2014: 22 · 2013: 10 · 2012: 8
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- U.S. Department of Defense
- U.S. Department of Agriculture
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS062019)
- Telemedicine and Advanced Technology Research Center
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Physical Sciences › Materials Science › Polymers and Plastics › Conducting polymers and applications
- Keywords
- neural probes, surface immobilization, covalent coating, silicon electrodes, gliosis, microglial activation, astrocytes, neuronal survival, axon density, chronic neural recording
- MeSH terms
- Animals, Astrocytes, Gliosis, Immunohistochemistry, Male, Models, Biological, Neurons, Rats, Sprague-Dawley, Microglia, Neural Cell Adhesion Molecule L1, Rats
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