BME 732 - Biotic Responses to Microelectrode Implants

medicineman's version from 2015-10-05 21:49

General Information

Question Answer
Electrode design requirements Long-term viability, minimal reduction in SNR, low tissue response, and minimal changes in electrode recording sites
Electrode materials Tungsten, Platinum, Platinum/Iridium, Ceramic, Silicon, Iridium Oxide, Gold, Silver, Stainless Steel, etc.
Problems with wireless electrodesHigh sample rates (lots of data), circuitry on top of electrode, high bandwidths, and heating
Speed of insertion High-speed insertion or very slow insertion
Biotic failure mechanisms Microglial activation and degeneration, astrogliosis, and blood-brain barrier disruption
Types of cells involved in neural tissue response Astrocytes and microglia
Astrocyte functions Provide growth cues to neurons during CNS development, provide mechanical support to neural structures, control chemical environment of neurons, neuronal signaling, modulate neuronal firing, and aid in the transfer of nutrients across the blood-brain barrier
Microglia Act primarily as cytotoxic cells killing pathogens or as phagocytes to degrade cellular debris and damaged matrix after injury
Tissue response to injuryAstroglial activation transforms the cells into a reactive phenotype. Enhanced migration, proliferation, hypertrophy, and an increase in mitochondria. Production of inflammatory factors. Phagocytose foreign material. Upregulate production of lytic enzymes to aid in degradation. Secrete multiple soluble factors that affect a variety of processes and signaling pathways
Response to severed blood vessels in the CNSMicroglia are indistinguishable from blood-born macrophages. Macrophage-like cells and microglia seem to perform the same functions. Microglia are known to secrete neurotrophic factors that aid in neuronal survival and growth

Tissue Stains

Question Answer
What are some commonly used markers for identifying injury response?Iba1, ED1, anti-ferritin, and GFAP
Iba1Binds to all microglial cells, irrespective of their activation or degeneration state. Provides and overall picture of the entire microglial population around implanted electrodes
ED1Binds to microglia and perivascular cells that are phagocytic. Provides a measure for quantifying numbers of active brain macrophages
Anti-ferritinLabels some microglia sometimes; in humans they are often dystrophic. Ferritin staining seems to be induced under certain injury/disease condition when the blood-brain barrier is disturbed and there is a need for iron sequestration
GFAPAstrocyte-specific cell marker

Implantation Damage

Question Answer
Acute response Mechanical trauma to insertion. This can be reduced by optimizing the speed of insertion, improving electrode geometry, and reducing the electrode size. Causes cell death, vascular disruption, and tissue compression
Chronic response Once the acute inflammatory response reduces, a chronic foreign body response is observed. Characterized by the presence of reactive astrocytes and activated microglia. Many cells in damaged neural tissue do not stain for GFAP which suggests the presence of large numbers of activated microglia
Glial scar formationGlial scars from in order to repair the blodd-brain barrier
NeuroinflammationNeuroinflammation has been shown to correlate poorly with electrode performance
Hemorrhage and electrode failurePermanent implantation of electrode arrays causes a disruption of the CNS microenvironment and blood-brain barrier, creating a high oxidative stress microenvironment. This corrosive microenvironment exacerbates existing electrode damage during manufacturing and eventually leads to failure

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