Cerebral Astrocyte Response to Micromachined Silicon Implants

Turner, James N.; Shain, William; Szarowski, Donald H.; Andersen, Maja Dam; Martins, Sarita; Isaacson, M.; Craighead, Harold G.

doi:10.1006/exnr.1998.6983

Cited by 536 publications

(546 citation statements)

References 42 publications

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“…We are able to release 0.5 µg/cm 2 Dex after each CV cycle and to a total of nearly 16 µg/cm 2 after 30 CV cycles. Based on most of the histological studies, the reactive region indicated by enhanced glial fibrillary acidic protein (GFAP), a key intermediate filament, activity around the neural electrode arrays has a radius of less than 500 µm [7,48]. A release of 0.5 µg/cm 2 Dex will result in average Dex concentration of 1 µM within 500 µm radius from the electrode.…”

Section: Resultsmentioning

confidence: 99%

“…The chronic application of these devices has been limited by their unpredictable failure over extended periods. Although the precise mechanism for this failure is not completely known, it is suggested that an undesirable brain tissue reaction to the device leads to the formation of a glial scar which then serves as a barrier to neural signal transduction [1][2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, as an anti-inflammatory substance, Dex reduces numerous pro-inflammatory cytokines, including IL-1β, IL-6, INF-γ and TNF-α [21]. Peripheral injections of Dex have been shown to effectively minimize the reactive tissue response to neural implants in the rat [22]. However, systemic injections have the obvious disadvantage of exposing the whole body to high dosages of the drug and its potential toxicity.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Wadhwa

Lagenaur

Cui

2006

Journal of Controlled Release

459

393

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Chronic recordings from micromachined neural electrode arrays often fail a few weeks after implantation primarily due to the formation of an astro-glial sheath around the implant. We propose a drug delivery system, from conducting polymer (CP) coatings on the electrode sites, to modulate the inflammatory implant-host tissue reaction. In this study, polypyrrole (PPy) based coatings for electrically controlled and local delivery of the ionic form of an anti-inflammatory drug, dexamethasone (Dex), was investigated. The drug was incorporated in PPy via electropolymerization of pyrrole and released in PBS using cyclic voltammetry (CV). FTIR analysis of the surface showed the presence of Dex and polypyrrole on the coated electrode. The thickness of the coated film was estimated to be ~50 nm by ellipsometry. We were able to release 0.5 µg/cm 2 Dex in 1 CV cycle and upto 92% Dex after 30 CV cycles. In-vitro studies and immunocytochemistry on murine glial cells suggest that the released drug lowers the count of reactive astrocytes to the same extent as the added drug. In addition, the released drug is not toxic to neurons as seen by healthy neuronal viability in the released drug treated cells.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Wadhwa

Lagenaur

Cui

2006

Journal of Controlled Release

459

393

View full text Add to dashboard Cite

show abstract

“…At a cellular level, it has been shown that activated, proliferating microglia appear around the implant site as early as 1-day post implantation [18,21,42]. These activated microglia are thought to gradually diminish both excess fluid and cellular debris 6 -8 days after the implant, although necrotic tissue has been observed up to 42 days later [41,44]. At later time points, typical inflammatory cells or hemorrhaging has not been observed [47], while others have documented neuronal cell loss and macrophages up to 112 days after the implant [6,41,42,44].…”

Section: Introductionmentioning

confidence: 99%

“…These activated microglia are thought to gradually diminish both excess fluid and cellular debris 6 -8 days after the implant, although necrotic tissue has been observed up to 42 days later [41,44]. At later time points, typical inflammatory cells or hemorrhaging has not been observed [47], while others have documented neuronal cell loss and macrophages up to 112 days after the implant [6,41,42,44]. As a testament to the transitory nature of this mechanically induced wound healing response, electrode tracks could not be found in animals after several months when the electrode was inserted and quickly removed [6,13,35,47].…”

Section: Introductionmentioning

confidence: 99%

Metabolic and behavioral deficits following a routine surgical procedure in rats

et al. 2007

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To test the hypothesis that functional metabolic deficits observed following surgical brain injury are associated with changes in cognitive performance in rodents, we performed serial imaging studies in parallel with behavioral measures in control animals and in animals with surgical implants. Memory function was assessed using the novel object recognition (NOR) test, administered 3 days prior to and 3, 7, 14, and 56 days after surgery. At each time point, general locomotion was also measured. Metabolic imaging with 18 F-fluorodeoxyglucose ([ 18 F]FDG) occurred 28 and 58 days after surgery. Animals with surgical implants performed significantly worse on tests of object recognition, while general locomotion was unaffected by the implant. There was a significant decrease in glucose uptake after surgery in most of the hemisphere ipsilateral to the implant relative to the contralateral hemisphere. At both time points, the most significant metabolic deficits occurred in the primary motor cortex (-25%; p<0.001), sensory cortex (-15%, p<0.001) and frontal cortex (-12%; p<0.001). Ipsilateral areas further from the site of insertion became progressively worse, including the sensory cortex, dorsal striatum and thalamus. This data was supported by a voxel-based analysis of the PET data, which revealed again a unilateral decrease in [ 18 F]FDG uptake that extended throughout the ipsilateral cortex and persisted for the duration of the 58-day study. Probe implantation in the striatum results in a widespread and long lasting decline in cortical glucose metabolism together with a persistent, injury-related deficit in the performance of a cognitive (object recognition) task in rats.

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Attachment of astroglial cells to microfabricated pillar arrays of different geometries

Turner

Dowell

Turner

et al. 2000

J. Biomed. Mater. Res.

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177

126

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We studied the attachment of astroglial cells on smooth silicon and arrays of silicon pillars and wells with various widths and separations. Standard semiconductor industry photolithographic techniques were used to fabricate pillar arrays and wells in single-crystal silicon. The resulting pillars varied in width from 0. 5 to 2.0 micrometer, had interpillar gaps of 1.0-5.0 micrometer, and were 1.0 micrometer in height. Arrays also contained 1.0-micromter-deep wells that were 0.5 micrometer in diameter and separated by 0.5-2.0 micrometer. Fluorescence, reflectance, and confocal light microscopies as well as scanning electron microscopy were used to quantify cell attachment, describe cell morphologies, and study the distribution of cytoskeletal proteins actin and vinculin on surfaces with pillars, wells, and smooth silicon. Seventy percent of LRM55 astroglial cells displayed a preference for pillars over smooth silicon, whereas only 40% preferred the wells to the smooth surfaces. Analysis of variance statistics performed on the data sets yielded values of p > approximately.5 for the comparison between pillar data sets and < approximately.0003 in the comparison between pillar and well data sets. Actin and vinculin distributions were highly polarized in cells found on pillar arrays. Scanning electron microscopy clearly demonstrated that cells made contact with the tops of the pillars and did not reach down into the spaces between pillars even when the interpillar gap was 5.0 microm. These experiments support the use of surface topography to direct the attachment, growth, and morphology of cells. These surfaces can be used to study fundamental cell properties such as cell attachment, proliferation, and gene expression. Such topography might also be used to modify implantable medical devices such as neural implants and lead to future developments in tissue engineering.

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Cerebral Astrocyte Response to Micromachined Silicon Implants

Cited by 536 publications

References 42 publications

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Metabolic and behavioral deficits following a routine surgical procedure in rats

Attachment of astroglial cells to microfabricated pillar arrays of different geometries

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