Inhibition of Na+/H+exchanger modulates microglial activation and scar formation following microelectrode implantation.

Objective.Intracortical microelectrodes are an important tool for neuroscience research and have great potential for clinical use. However, the use of microelectrode arrays to treat neurological disorders and control prosthetics is limited by biological challenges such as glial scarring, which can impair chronic recording performance. Microglia activation is an early and prominent contributor to glial scarring. After insertion of an intracortical microelectrode, nearby microglia transition into a state of activation, migrate, and encapsulate the device. Na+/H+exchanger isoform-1 (NHE-1) is involved in various microglial functions, including their polarity and motility, and has been implicated in pro-inflammatory responses to tissue injury. HOE-642 (cariporide) is an inhibitor of NHE-1 and has been shown to depress microglial activation and inflammatory response in brain injury models.Approach.In this study, the effects of HOE-642 treatment on microglial interactions to intracortical microelectrodes was evaluated using two-photon microscopyin vivo.Main results.The rate at which microglia processes and soma migrate in response to electrode implantation was unaffected by HOE-642 administration. However, HOE-642 administration effectively reduced the radius of microglia activation at 72 h post-implantation from 222.2µm to 177.9µm. Furthermore, treatment with HOE-642 significantly reduced microglial encapsulation of implanted devices at 5 h post-insertion from 50.7 ± 6.0% to 8.9 ± 6.1%, which suggests an NHE-1-specific mechanism mediating microglia reactivity and gliosis during implantation injury.Significance.This study implicates NHE-1 as a potential target of interest in microglial reactivity and HOE-642 as a potential treatment to attenuate the glial response and scar formation around implanted intracortical microelectrodes.

Cuprizone-induced oligodendrocyte loss and demyelination impairs recording performance of chronically implanted neural interfaces.

Biological inflammation induced during penetrating cortical injury can disrupt functional neuronal and glial activity within the cortex, resulting in potential recording failure of chronically implanted neural interfaces. Oligodendrocytes provide critical support for neuronal health and function through direct contact with neuronal soma and axons within the cortex. Given their fundamental role to regulate neuronal activity via myelin, coupled with their heightened vulnerability to metabolic brain injury due to high energetic demands, oligodendrocytes are hypothesized as a possible source of biological failure in declining recording performances of intracortical microelectrode devices. To determine the extent of their contribution to neuronal activity and function, a cuprizone-inducible model of oligodendrocyte depletion and demyelination in mice was performed prior to microelectrode implantation. At 5 weeks of cuprizone exposure, mice demonstrated significantly reduced cortical oligodendrocyte density and myelin expression. Mice were then implanted with functional recording microelectrodes in the visual cortex and neuronal activity was evaluated up to 7 weeks alongside continued cuprizone administration. Cuprizone-induced oligodendrocyte loss and demyelination was associated with significantly reduced recording performances at the onset of implantation, which remained relatively stable over time. In contast, recording performances for mice on a normal diet were intially elevated before decreasing over time to the recording level of tcuprizone-treated mice. Further electrophysiological analysis revealed deficits in multi-unit firing rates, frequency-dependent disruptions in neuronal oscillations, and altered laminar communication within the cortex of cuprizone-treated mice. Post-mortem immunohistochemistry revealed robust depletion of oligodendrocytes around implanted microelectrode arrays alongside comparable neuronal densities to control mice, suggesting that oligodendrocyte loss was a possible contributor to chronically impaired device performances. This study highlights potentially significant contributions from the oligodendrocyte lineage population concerning the biological integration and long-term functional performance of neural interfacing technology.

Quality Assurance Sampling Plans in US Stockpiles for Personal Protective Equipment: A Computer Simulation to Examine Degradation Rates.

Medical countermeasure stockpiles in the United States are designed to support healthcare workers and the public during public health emergencies; they include supplies of personal protective equipment (PPE). As part of typical PPE manufacturing processes, appropriate test methods are used to ensure that the devices provide adequate protective performance. At the time of manufacture, performance is often measured and weighed against an objective standard of quality, resulting in a pass or fail attribute being assigned to individual PPE items and thence to production lots. Incorporating periodic performance testing for stockpiled PPE can ensure that they maintain their protective qualities and integrity over time while in storage. There is an absence of guidance regarding how to design quality assurance programs for stockpiled PPE. The applicability of the Lot Quality Assurance Sampling (LQAS) approach to stockpiled PPE was examined in a previous study that compared and contrasted different sample sizes in recovering the true percentage of defective units in large lots in the LQAS framework. The current study carries this line of inquiry forward by integrating PPE degradation over time and comparing different sampling time intervals in recovering the true underlying degradation rate. The results suggest that product degradation is more easily detected when tested at shorter time intervals and for higher degradation rates. They further suggest that sampling interval groupings can be made based on the proficiency with which they recover the true underlying degradation rate.

Quality Assurance Sampling Plans in US Stockpiles for Personal Protective Equipment.

Personal protective equipment (PPE) stockpiles in the United States were established to facilitate rapid deployment of medical assets to sites affected by public health emergencies. Large quantities of PPE were introduced into US stockpiles because of the need to protect healthcare and other professionals during these events. Because most stockpiled PPE was acquired during, or immediately following, large-scale public health events, such as pandemic influenza planning (2005-20080), SARS (2003), H1N1 (2009-10), and Ebola (2014-15), aging PPE poses a significant problem. PPE such as N95 filtering face piece respirators were not designed to be stored for long periods, and much of the currently stored PPE has exceeded its manufacturer-assigned shelf life. Given the significant investment in the procurement and storage of PPE, along with projections of consumption during public health emergencies, discarding large quantities of potentially viable PPE is not an attractive option. Although shelf-life extension programs exist for other stockpiled medical assets, no such option is currently available for stockpiled PPE. This article posits stockpile quality assurance sampling plans as a mechanism through which shelf-life extension programs for stockpiled PPE may be achieved. We discuss some of the nuances that should be considered when developing a plan tailored to stockpiles and provide basic decision tools that may be used in the context of a quality assurance program tailored to stockpiled PPE. We also explore basic information by comparing and contrasting different sample size options.