Abstract
It has been hypothesized that physiological shear forces acting on medical devices implanted in the brain significantly accelerate the rate to device failure in patients with chronically indwelling neuroprosthetics. In hydrocephalus shunt devices, shear forces arise from cerebrospinal fluid flow. The shunt’s unacceptably high failure rate is mostly due to obstruction with adherent inflammatory cells. Astrocytes are the dominant cell type bound directly to obstructing shunts, rapidly manipulating their activation via shear stress-dependent cytokine secretion. Here we developed a total internal reflection fluorescence microscopy combined with a microfluidic shear device chip (MSDC) for quantitative analysis and direct spatial-temporal mapping of secreted cytokines at the single-cell level under physiological shear stress to identify the root cause for shunt failure. Real-time secretion imaging at 1-min time intervals enabled successful detection of a significant increase of astrocyte IL-6 cytokine secretion under shear stress greater than 0.5 dyne/cm2, validating our hypothesis and highlighting the importance of reducing shear stress activation of cells.
Highlights
It has been hypothesized that physiological shear forces acting on medical devices implanted in the brain significantly accelerate the rate to device failure in patients with chronically indwelling neuroprosthetics
Along the shunt hole/cerebrospinal fluid (CSF) interface, astrocytes are simultaneously exposed to fluid flow shear stress and TNF-α/IL1β cytokine stimulation secreted from activated microglia/macrophages on the shunt surface[26,27]
Physiological shear stress can be created by fluid flow induction at a predetermined rate, in the presence of TNF-α/IL1β to determine the influence of shear stress on specific astrocyte phenotypes
Summary
It has been hypothesized that physiological shear forces acting on medical devices implanted in the brain significantly accelerate the rate to device failure in patients with chronically indwelling neuroprosthetics. It is reasonable to hypothesize that along the shunt/CSF interface, shear stress-activated astrocytes secrete cytokines which in turn cause heightened activation and proliferation of other astrocytes and eventually accelerates glial scar formation on the device surface leading to high shunt failure rates. These approaches cannot currently offer either a time interval of shorter than a few hours nor simultaneous real-time observation of a second cellular variable (e.g., cell physiological states, intercellular adhesion molecule expression) at the time of cytokine secretion To successfully address this issue in fluorescence immunoassay, Ohara and colleagues have taken advantage of near-field excitation in total internal reflection fluorescence microscopy (TIR-FM)[21,22,23]. Sandwich fluorescence immunoassay is a more sensitive and specific approach for small molecules like cytokines than the plasmonic approach, since the plasmonic signal is proportional to the molecular weight of the binding molecule
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
