The roles of blood-derived macrophages and resident microglia in the neuroinflammatory response to implanted intracortical microelectrodes.

Resident microglia and blood-borne macrophages have both been implicated to play a dominant role in mediating the neuroinflammatory response affecting implanted intracortical microelectrodes. However, the distinction between each cell type has not been demonstrated due to a lack of discriminating cellular markers. Understanding the subtle differences of each cell population in mediating neuroinflammation can aid in determining the appropriate therapeutic approaches to improve microelectrode performance. Therefore, the goal of this study is to characterize the role of infiltrating blood-derived cells, specifically macrophages, in mediating neuroinflammation following intracortical microelectrode implantation. Interestingly, we found no correlation between microglia and neuron populations at the microelectrode-tissue interface. On the other hand, blood-borne macrophages consistently dominated the infiltrating cell population following microelectrode implantation. Most importantly, we found a correlation between increased populations of blood-derived cells (including the total macrophage population) and neuron loss at the microelectrode-tissue interface. Specifically, the total macrophage population was greatest at two and sixteen weeks post implantation, at the same time points when we observed the lowest densities of neuronal survival in closest proximity to the implant. Together, our results suggest a dominant role of infiltrating macrophages, and not resident microglia, in mediating neurodegeneration following microelectrode implantation.

[1]  J. Donoghue,et al.  Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates , 2013, Journal of neural engineering.

[2]  U. Hanisch,et al.  Microglia as a source and target of cytokines , 2002, Glia.

[3]  D. Remick,et al.  Differences in normal values for murine white blood cell counts and other hematological parameters based on sampling site , 2001, Inflammation Research.

[4]  Patrick A Tresco,et al.  Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays. , 2011, Progress in brain research.

[5]  R. Ransohoff,et al.  Inflammatory cell trafficking across the blood–brain barrier: chemokine regulation and in vitro models , 2012, Immunological reviews.

[6]  H. Kettenmann,et al.  Physiology of microglia. , 2011, Physiological reviews.

[7]  J Miller,et al.  Minocycline increases quality and longevity of chronic neural recordings , 2007, Journal of neural engineering.

[8]  Michael L. Anderson Neural reuse: A fundamental organizational principle of the brain , 2010, Behavioral and Brain Sciences.

[9]  E. Ling,et al.  Microglial activation and its implications in the brain diseases. , 2007, Current medicinal chemistry.

[10]  S. Gordon,et al.  Macrosialin, a macrophage-restricted membrane sialoprotein differentially glycosylated in response to inflammatory stimuli [published erratum appears in J Exp Med 1992 Jan 1;175(1):309] , 1991, The Journal of experimental medicine.

[11]  S. Manna,et al.  Resveratrol Suppresses TNF-Induced Activation of Nuclear Transcription Factors NF-κB, Activator Protein-1, and Apoptosis: Potential Role of Reactive Oxygen Intermediates and Lipid Peroxidation1 , 2000, The Journal of Immunology.

[12]  David C. Martin,et al.  Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4-ethylenedioxythiophene) (PEDOT) film , 2006, Journal of neural engineering.

[13]  B D Burns,et al.  Recording for several days from single cortical neurons in completely unrestrained cats. , 1974, Electroencephalography and clinical neurophysiology.

[14]  D. Szarowski,et al.  Brain responses to micro-machined silicon devices , 2003, Brain Research.

[15]  R. Wm A Molecular Perspective on Understanding and Modulating the Performance of Chronic Central Nervous System (CNS) Recording Electrodes -- Indwelling Neural Implants: Strategies for Contending with the In Vivo Environment , 2008 .

[16]  A. Levey,et al.  Implanted neural electrodes cause chronic, local inflammation that is correlated with local neurodegeneration , 2009, Journal of neural engineering.

[17]  Garrett B Stanley,et al.  The impact of chronic blood-brain barrier breach on intracortical electrode function. , 2013, Biomaterials.

[18]  M. Simard,et al.  The neurobiology of glia in the context of water and ion homeostasis , 2004, Neuroscience.

[19]  P. Horner,et al.  Early Reduction of Microglia Activation by Irradiation in a Model of Chronic Glaucoma , 2012, PloS one.

[20]  Florian Solzbacher,et al.  A comparison of the tissue response to chronically implanted Parylene-C-coated and uncoated planar silicon microelectrode arrays in rat cortex. , 2010, Biomaterials.

[21]  E. Hansson,et al.  Astrocyte–endothelial interactions at the blood–brain barrier , 2006, Nature Reviews Neuroscience.

[22]  David C. Martin,et al.  Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays , 2005, Experimental Neurology.

[23]  S. Cogan Neural stimulation and recording electrodes. , 2008, Annual review of biomedical engineering.

[24]  K. Horn,et al.  Overcoming Macrophage-Mediated Axonal Dieback Following CNS Injury , 2009, The Journal of Neuroscience.

[25]  Nicolas Y. Masse,et al.  Reach and grasp by people with tetraplegia using a neurally controlled robotic arm , 2012, Nature.

[26]  P. Davies,et al.  Resveratrol mitigates lipopolysaccharide‐ and Aβ‐mediated microglial inflammation by inhibiting the TLR4/NF‐κB/STAT signaling cascade , 2012, Journal of neurochemistry.

[27]  Andrew B Schwartz,et al.  Cortical neural prosthetics. , 2004, Annual review of neuroscience.

[28]  C. Haas,et al.  Bone Marrow Cell Recruitment to the Brain in the Absence of Irradiation or Parabiosis Bias , 2013, PloS one.

[29]  G. Landreth,et al.  The role of microglia in amyloid clearance from the AD brain , 2010, Journal of Neural Transmission.

[30]  Michael J. Black,et al.  Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array , 2011 .

[31]  Hugues Duffau,et al.  Brain mapping in tumors: Intraoperative or extraoperative? , 2013, Epilepsia.

[32]  J. Mandell,et al.  Phagocytic clearance in neurodegeneration. , 2011, The American journal of pathology.

[33]  Max Gassmann,et al.  Astrocyte responses to injury: VEGF simultaneously modulates cell death and proliferation. , 2008, American journal of physiology. Regulatory, integrative and comparative physiology.

[34]  Ravi V. Bellamkonda,et al.  Dexamethasone-coated neural probes elicit attenuated inflammatory response and neuronal loss compared to uncoated neural probes , 2007, Brain Research.

[35]  Patrick A Tresco,et al.  Quantitative analysis of the tissue response to chronically implanted microwire electrodes in rat cortex. , 2010, Biomaterials.

[36]  I Schmid,et al.  Dead cell discrimination with 7-amino-actinomycin D in combination with dual color immunofluorescence in single laser flow cytometry. , 1992, Cytometry.

[37]  C. Glass,et al.  Microglial cell origin and phenotypes in health and disease , 2011, Nature Reviews Immunology.

[38]  Markus G. Manz,et al.  Development of Monocytes, Macrophages, and Dendritic Cells , 2010, Science.

[39]  Jeffrey R Capadona,et al.  A comparison of neuroinflammation to implanted microelectrodes in rat and mouse models. , 2014, Biomaterials.

[40]  Kelsey A. Potter,et al.  Curcumin-releasing mechanically adaptive intracortical implants improve the proximal neuronal density and blood-brain barrier stability. , 2014, Acta biomaterialia.

[41]  D. Wesson,et al.  Encoding and Representation of Intranasal CO2 in the Mouse Olfactory Cortex , 2013, The Journal of Neuroscience.

[42]  Kortaro Tanaka,et al.  Enhanced Expression of Iba1, Ionized Calcium-Binding Adapter Molecule 1, After Transient Focal Cerebral Ischemia In Rat Brain , 2001, Stroke.

[43]  Eva Syková,et al.  Diffusion barriers evoked in the rat cortex by reactive astrogliosis , 1999, Glia.

[44]  N. Van Rooijen,et al.  Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. , 1994, Journal of immunological methods.

[45]  C. Power,et al.  For Personal Use. Only Reproduce with Permission from Elsevier Ltd Minocycline and Neurological Diseases Minocycline in Animal Models the Promise of Minocycline in Neurology , 2022 .

[46]  Christine L Larson,et al.  Functional coupling of simultaneous electrical and metabolic activity in the human brain , 2004, Human brain mapping.

[47]  Michael J. Black,et al.  Assistive technology and robotic control using motor cortex ensemble‐based neural interface systems in humans with tetraplegia , 2007, The Journal of physiology.

[48]  K. Horn,et al.  Another Barrier to Regeneration in the CNS: Activated Macrophages Induce Extensive Retraction of Dystrophic Axons through Direct Physical Interactions , 2008, The Journal of Neuroscience.

[49]  C. Schachtrup,et al.  Fibrinogen Triggers Astrocyte Scar Formation by Promoting the Availability of Active TGF-β after Vascular Damage , 2010, The Journal of Neuroscience.

[50]  R. Bellamkonda,et al.  A Molecular Perspective on Understanding and Modulating the Performance of Chronic Central Nervous System (CNS) Recording Electrodes , 2008 .

[51]  W. Hader,et al.  Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell‐microglia interaction , 2005, Journal of leukocyte biology.

[52]  Justin C. Sanchez,et al.  Abiotic-biotic characterization of Pt/Ir microelectrode arrays in chronic implants , 2014, Front. Neuroeng..

[53]  A. Nimmerjahn,et al.  The Role of Microglia in the Healthy Brain , 2011, The Journal of Neuroscience.

[54]  M. Norenberg,et al.  Astrocyte Responses to CNS Injury , 1994, Journal of neuropathology and experimental neurology.

[55]  Jeffrey R. Capadona,et al.  Reduction of autofluorescence at the microelectrode–cortical tissue interface improves antibody detection , 2012, Journal of Neuroscience Methods.

[56]  Justin C. Sanchez,et al.  Comprehensive characterization and failure modes of tungsten microwire arrays in chronic neural implants , 2012, Journal of neural engineering.

[57]  Wei Li,et al.  Role of microglia in CNS inflammation , 2011, FEBS letters.

[58]  Jeffrey R Capadona,et al.  The effect of resveratrol on neurodegeneration and blood brain barrier stability surrounding intracortical microelectrodes. , 2013, Biomaterials.

[59]  G. C. McConnell Chronic inflammation surrounding intra-cortical electrodes is correlated with a local, neurodegenerative state , 2008 .

[60]  Jon A. Mukand,et al.  Neuronal ensemble control of prosthetic devices by a human with tetraplegia , 2006, Nature.

[61]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[62]  D.B. McCreery,et al.  Evaluation of the stability of intracortical microelectrode arrays , 2006, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[63]  Deborah S. Barkauskas,et al.  High-resolution intravital imaging reveals that blood-derived macrophages but not resident microglia facilitate secondary axonal dieback in traumatic spinal cord injury , 2014, Experimental Neurology.

[64]  A. Hao,et al.  Microglia--friend or foe. , 2011, Frontiers in bioscience.

[65]  Kelsey A. Potter,et al.  Stab injury and device implantation within the brain results in inversely multiphasic neuroinflammatory and neurodegenerative responses , 2012, Journal of neural engineering.

[66]  Michael J. Black,et al.  Neural control of computer cursor velocity by decoding motor cortical spiking activity in humans with tetraplegia , 2008, Journal of neural engineering.

[67]  F. Rossi,et al.  Local self-renewal can sustain CNS microglia maintenance and function throughout adult life , 2007, Nature Neuroscience.

[68]  G. Buzsáki Large-scale recording of neuronal ensembles , 2004, Nature Neuroscience.

[69]  Jeffrey R Capadona,et al.  The Effect of Residual Endotoxin Contamination on the Neuroinflammatory Response to Sterilized Intracortical Microelectrodes. , 2014, Journal of materials chemistry. B.