Dexamethasone treatment reduces astroglia responses to inserted neuroprosthetic devices in rat neocortex

Spataro, Leah E.; Dilgen, J.; Retterer, Scott T.; Spence, Andrew J.; Isaacson, M.; Turner, James N.; Shain, William

doi:10.1016/j.expneurol.2004.08.037

Cited by 192 publications

(167 citation statements)

References 47 publications

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“…Second, prior work on neuroprosthetic devices appears to suggest that continuous delivery of DEX might not be necessary for long-term benefits. [43][44][45] Needle pricks performed 10 days after probe insertion induced clear K + spikes and corresponding glucose dips ( Figure 6): 87% of the fifteen K + spikes were accompanied by a quantifiable glucose dip (Table 1). Figure 6 confirms that the benefits of DEX retrodialysis for monitoring K + and glucose in the context of SD outlast the DEX retrodialysis itself.…”

Section: Sd-associated Transients 10 Days After Probe Insertion Micrmentioning

confidence: 99%

Enhancing Continuous Online Microdialysis Using Dexamethasone: Measurement of Dynamic Neurometabolic Changes during Spreading Depolarization

Varner

Leong

Jaquins-Gerstl

et al. 2017

ACS Chem. Neurosci.

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Microdialysis is well established in chemical neuroscience as a mainstay technology for real time intracranial chemical monitoring in both animal models and human patients. The capabilities of microdialysis sampling have the potential to be further enhanced through mitigation of the penetration injury unavoidably caused by the insertion of microdialysis probes into brain tissue. Herein, we show that dexamethasone retrodialysis in the rat cortex enhances the microdialysis detection of K+ and glucose transients induced by spreading depolarization. Once inserted, the probes were perfused continuously (1.67 μL/min) either with or without dexamethasone. Without dexamethasone, glucose transients were too small to reliably quantify at 5 days after probe insertion. With dexamethasone, robust K+ and glucose transients were readily quantified at 2 hrs, 5 days, and 10 days after probe insertion. Although the amplitudes of the K+ transients declined day-to-day following probe insertion, amplitudes of the glucose transients were consistent. Immunohistochemistry and fluorescence microscopy confirm that dexamethasone is highly effective at preventing ischemia and gliosis in the vicinity of microdialysis probes implanted for 10 days.

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Section: Sd-associated Transients 10 Days After Probe Insertion Micrmentioning

confidence: 99%

Enhancing Continuous Online Microdialysis Using Dexamethasone: Measurement of Dynamic Neurometabolic Changes during Spreading Depolarization

Varner

Leong

Jaquins-Gerstl

et al. 2017

ACS Chem. Neurosci.

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“…The failure of implanted neural probes over time can be attributed to neuronal loss around the probe including both neuron cell body loss and neural process loss (Liu et al, 1999;Schwartz, 2004;Spataro et al, 2005). Therefore, to maintain long-term recording stability, reactive gliosis and other inflammatory processes around the electrode need to be minimized.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone-coated neural probes elicit attenuated inflammatory response and neuronal loss compared to uncoated neural probes

Zhong¹,

Bellamkonda²

2007

Brain Research

286

254

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Glial scar formation around implanted silicon neural probes compromises their ability to facilitate long-term recordings. One approach to modulate the tissue reaction around implanted probes in the brain is to develop probe coatings that locally release antiinflammatory drugs. In this study, we developed a nitrocellulose-based coating for the local delivery of the anti-inflammatory drug dexamethasone (DEX). Silicon neural probes with and without nitrocellulose-DEX coatings were implanted into rat brains, and inflammatory response was evaluated 1 week and 4 weeks post implantation. DEX coatings significantly reduced the reactivity of microglia and macrophages one week post implantation as evidenced by ED1 immunostaining. CS56 staining demonstrated that DEX treatment significantly reduced chondroitin sulfate proteoglycan (CSPG) expression one week post implantation. Both at one week and at four week time points, GFAP staining for reactive astrocytes and neurofilament (NF) staining revealed that local DEX treatment significantly attenuated astroglial response and reduced neuronal loss in the vicinity of the probes. Weak ED1, neurocan, and NG2 positive signal was detected four weeks post implantation for both coated and uncoated probes, suggesting a stabilization of the inflammatory response over time in this implant model. In conclusion, this study demonstrates that the nitrocellulose-DEX coating can effectively attenuate the inflammatory response to the implanted neural probes, and reduce neuronal loss in the vicinity of the coated probes. Thus anti-inflammatory probe coatings may represent a promising approach to attenuate astroglial scar and reduce neural loss around implanted neural probes.

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“…This complexity presents a fundamental challenge to studies that require quantitative image-based measurements at the tissue scale. Examples of such studies include quantifying the location and distribution of cells in the neural stem-cell niche (Fuchs et al, 2004) and the cancer stem cell microenvironment (Calabrese et al, 2007), cell relationships associated with the bloodbrain barrier (Iadecola 2004), and changes in cell associations with injury or disease (Spataro et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Associative image analysis: A method for automated quantification of 3D multi-parameter images of brain tissue

Bjornsson

Lin

Al-Kofahi

et al. 2008

Journal of Neuroscience Methods

103

111

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Brain structural complexity has confounded prior efforts to extract quantitative image-based measurements. We present a systematic 'divide and conquer' methodology for analyzing threedimensional (3D) multi-parameter images of brain tissue to delineate and classify key structures, and compute quantitative associations among them. To demonstrate the method, thick (~100 μm) slices of rat brain tissue were labeled using 3 -5 fluorescent signals, and imaged using spectral confocal microscopy and unmixing algorithms. Automated 3D segmentation and tracing algorithms were used to delineate cell nuclei, vasculature, and cell processes. From these segmentations, a set of 23 intrinsic and 8 associative image-based measurements was computed for each cell. These features were used to classify astrocytes, microglia, neurons, and endothelial cells. Associations among cells and between cells and vasculature were computed and represented as graphical networks to enable further analysis. The automated results were validated using a graphical interface that permits investigator inspection and corrective editing of each cell in 3D. Nuclear counting accuracy was >89%, and cell classification accuracy ranged from 81-92% depending on cell type. We present a software system named FARSIGHT implementing our methodology. Its output is a detailed XML file containing measurements that may be used for diverse quantitative hypothesis-driven and exploratory studies of the central nervous system.

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Dexamethasone treatment reduces astroglia responses to inserted neuroprosthetic devices in rat neocortex

Cited by 192 publications

References 47 publications

Enhancing Continuous Online Microdialysis Using Dexamethasone: Measurement of Dynamic Neurometabolic Changes during Spreading Depolarization

Enhancing Continuous Online Microdialysis Using Dexamethasone: Measurement of Dynamic Neurometabolic Changes during Spreading Depolarization

Dexamethasone-coated neural probes elicit attenuated inflammatory response and neuronal loss compared to uncoated neural probes

Associative image analysis: A method for automated quantification of 3D multi-parameter images of brain tissue

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