Stable interconnection to neurons in vivo over long time-periods is critical for the success of future advanced neuroelectronic applications. The inevitable foreign body reaction towards implanted materials challenges the stability and an active intervention strategy would be desirable to treat inflammation locally. Here, we investigate whether controlled release of the anti-inflammatory drug Dexamethasone from flexible neural microelectrodes in the rat hippocampus has an impact on probe-tissue integration over 12 weeks of implantation. The drug was stored in a conducting polymer coating (PEDOT/Dex), selectively deposited on the electrode sites of neural probes, and released on weekly basis by applying a cyclic voltammetry signal in three electrode configuration in fully awake animals. Dex-functionalized probes provided stable recordings and impedance characteristics over the entire chronic study. Histological evaluation after 12 weeks of implantation revealed an overall low degree of inflammation around all flexible probes whereas electrodes exposed to active drug release protocols did have neurons closer to the electrode sites compared to controls. The combination of flexible probe technology with anti-inflammatory coatings accordingly offers a promising approach for enabling long-term stable neural interfaces.
Abstract. With the increase in economic development over the past thirty years, many large cities in eastern and southwestern China are experiencing increased haze events and atmospheric pollution, causing significant impacts on the regional environment and even climate. However, knowledge on the aerosol physical and chemical properties in heavy haze conditions is still insufficient. In this study, two winter heavy haze events in Beijing that occurred in 2011 and 2012 were selected and investigated by using the ground-based remote sensing measurements. We used a CIMEL CE318 sunsky radiometer to retrieve haze aerosol optical, physical and chemical properties, including aerosol optical depth (AOD), size distribution, complex refractive indices and aerosol fractions identified as black carbon (BC), brown carbon (BrC), mineral dust (DU), ammonium sulfate-like (AS) components and aerosol water content (AW). The retrieval results from a total of five haze days showed that the aerosol loading and properties during the two winter haze events were comparable. Therefore, average heavy haze property parameters were drawn to present a research case for future studies. The average AOD is about 3.0 at 440 nm, and the Ångström exponent is 1.3 from 440 to 870 nm. The fine-mode AOD is 2.8 corresponding to a fine-mode fraction of 0.93. The coarse particles occupied a considerable volume fraction of the bimodal size distribution in winter haze events, with the mean particle radius of 0.21 and 2.9 µm for the fine and coarse modes respectively. The real part of the refractive indices exhibited a relatively flat spectral behavior with an average value of 1.48 from 440 to 1020 nm. The imaginary part showed spectral variation, with the value at 440 nm (about 0.013) higher than the other three wavelengths (about 0.008 at 675 nm). The aerosol composition retrieval results showed that volume fractions of BC, BrC, DU, AS and AW are 1, 2, 49, 15 and 33 %, respectively, on average for the investigated haze events. The preliminary uncertainty estimation and comparison of these remote sensing results with in situ BC and PM 2.5 measurements are also presented in the paper.
A long term functional and reliable coupling between neural tissue and implanted microelectrodes is the key issue in acquiring neural electrophysiological signals or therapeutically excite neural tissue. The currently often used rigid micro-electrodes are thought to cause a severe foreign body reaction resulting in a thick glial scar and consequently a poor tissue-electrode coupling in the chronic phase. We hypothesize, that this adverse effect might be remedied by probes compliant to the soft brain tissue, i.e., replacing rigid electrodes by flexible ones. Unfortunately, this flexibility comes at the price of a low stiffness, which makes targeted low trauma implantation very challenging. In this study, we demonstrate an adaptable and simple method to implant extremely flexible microprobes even to deep areas of rat's brain. Implantation of flexible probes is achieved by rod supported stereotactic insertion fostered by a hydrogel (2% agarose in PBS) cushion on the exposed skull. We were thus able to implant very flexible micro-probes in 70 rats as deep as the rodent's subthalamic nucleus. This work describes in detail the procedures and steps needed for minimal invasive, but reliable implantation of flexible probes.
In neural prosthetics and stereotactic neurosurgery, intracortical electrodes are often utilized for delivering therapeutic electrical pulses, and recording neural electrophysiological signals. Unfortunately, neuroinflammation impairs the neuron-electrode-interface by developing a compact glial encapsulation around the implants in long term. At present, analyzing this immune reaction is only feasible with post-mortem histology; currently no means for specific in vivo monitoring exist and most applicable imaging modalities can not provide information in deep brain regions. Optical coherence tomography (OCT) is a well established imaging modality for in vivo studies, providing cellular resolution and up to 1.2 mm imaging depth in brain tissue. A fiber based spectral domain OCT was shown to be capable of minimally invasive brain imaging. In the present study, we propose to use a fiber based spectral domain OCT to monitor the progression of the tissue's immune response through scar encapsulation progress in a rat animal model. A fine fiber catheter was implanted in rat brain together with a flexible polyimide microelectrode in sight both of which acts as a foreign body and induces the brain tissue immune reaction. OCT signals were collected from animals up to 12 weeks after implantation and thus gliotic scarring in vivo monitored for that time. Preliminary data showed a significant enhancement of the OCT backscattering signal during the first 3 weeks after implantation, and increased attenuation factor of the sampled tissue due to the glial scar formation.
Density of fine mode particles is an important physical parameter. However, its measurement and validation in the actual atmosphere are still difficult. In this study, the measurements at Shouxian, Anhui province, China (32.56°N, 116.78°E, elevation 22.7 m) in winter, are used for density retrieval and quality control. The effective density and number size distribution of fine mode aerosol can be obtained in real time, by using the scanning mobility particle sizer and aerodynamic particle sizer. During the experiment, the average density is about 1.66 ± 0.15 g/cm 3 with the uncertainty of 0.19 g/cm 3 calculated from the residuals in the overlap region of scanning mobility and aerodynamic particle sizers. A multi-instrument measurement and quality control scheme is proposed to identify large measurement uncertainties. The extinction and scattering coefficients calculated from the merged fine particle number size distributions by Mie theory are comparable with the measurements from cavity-enhanced albedometer. The differences between the calculated and observed scattering and extinction coefficients are less than 2%. Meanwhile, the deduced aerosol complex refractive index n and k are obtained by minimizing the sum of squared residuals of extinction and scattering coefficients and comparable with the values retrieved from the Sun-sky radiometer CE318 measurements. The correlation coefficient on n is 0.72. However, the correlation on k is not optimized, explained by the influence of anthropogenic aerosol particles with strong absorption near ground and the poor accuracy of k. Compared with independent observations, a good agreement between the optical parameters is also obtained.
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