Neural interface technologies that link the nervous system and the outside world by either stimulating or recording from neural tissue, show great promise for patients suffering from various neurological injuries or disorders. However, the poor recording stability and longevity of neural interface devices (neural probes) is an imminent obstacle to their advance in widespread clinical applications. The dominant factor that affects chronic neural recordings has been reported to be the inflammatory tissue response including neuronal loss and gliosis at the electrode/tissue interface.
In this study, we proposed to modify the surface of neural probes with the neural adhesion molecule L1. The L1 molecule is known to specifically promote neurite outgrowth and neuronal survival. We hypothesized that surface immobilization of L1, may introduce a neuron friendly environment to maintain healthy neuronal density and promote neurite outgrowth around the recording electrodes. Consequently, this phenomenon could reduce gliosis formation. Silane chemistry and the heterobifunctional coupling agent, 4-Maleimidobutyric acid N-hydroxysuccinimide ester (GMBS), were used to covalently bind L1 onto the silicon surface. Polyethylene glycol (PEG)-NH2 was co-immobilized to cap unreacted GMBS groups and prevent non-specific cell attachment. Primary murine neurons and astrocytes were cultured on L1 modified and control surfaces. The L1 surfaces showed promoted neuronal attachment and neurite outgrowth but significantly reduced astrocyte attachment relative to controls. L1 vs. non modified control probes were implanted in the rat motor cortex for 1, 4, and 8 weeks. Extensive immunohistochemistry and quantitative image analysis were performed to assess the brain tissue response to implants. The results showed that the L1 modified probes had no loss of neurons around the implant interface and showed a significant increase of axonal density compared to the control at all time points. Additionally, significantly reduced glia cell activation and recruitment was observed at the vicinity of the L1 modified probes. As a final step, we have developed a method to evaluate the chronic recording performance of neural probes in the rat somatosensory cortex from whisker stimulation and cortical recordings.
Based on our results we conclude that the L1 biomolecule shows neuroprotective and neurogenerative properties while inhibiting gliosis. The L1 surface coating can be a promising strategy to improve the biocompatibility of all types of neural probes and their chronic performance in the brain.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04122010-134858 |
| Date | 25 June 2010 |
| Creators | Azemi, Erdrin |
| Contributors | Simon Watkins, Carl Lagenaur, Kacey Marra, Douglas Weber, Xinyan Tracy Cui |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04122010-134858/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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