Abstract Implantable neural electrode technologies for chronic neural recordings can restore functional control to paralysis and limb loss victims through brain-machine interfaces. These probes, ...however, have high failure rates partly due to the biological responses to the probe which generates an inflammatory scar and subsequent neuronal cell death. L1 is a neuronal specific cell adhesion molecule and has been shown to minimize glial scar formation and promote electrode-neuron integration when covalently attached to the surface of neural probes. In this work, the acute microglial response to L1-coated neural probes was evaluated in vivo by implanting coated devices into the cortex of mice with fluorescently labeled microglia, and tracking microglial dynamics with multi-photon microscopy for the ensuing 6 h in order to understand L1's cellular mechanisms of action. Microglia became activated immediately after implantation, extending processes towards both L1-coated and uncoated control probes at similar velocities. After the processes made contact with the probes, microglial processes expanded to cover 47.7% of the control probes' surfaces. For L1-coated probes, however, there was a statistically significant 83% reduction in microglial surface coverage. This effect was sustained through the experiment. At 6 h post-implant, the radius of microglia activation was reduced for the L1 probes by 20%, shifting from 130.0 to 103.5 μm with the coating. Microglia as far as 270 μm from the implant site displayed significantly lower morphological characteristics of activation for the L1 group. These results suggest that the L1 surface treatment works in an acute setting by microglial mediated mechanisms.
There are limited data comparing the prognosis and fertility outcomes of the patients with early cervical cancer treated by trans-vaginal radical trachelectomy (VRT) or abdominal radical ...trachelectomy (ART).The objective of this study was to compare the surgical and pathologic characteristics, the prognosis and fertility outcomes of the patients treated by VRT or ART.
Matched-case study based on a prospectively maintained database of patients underwent radical trachelectomy in 10 centres of China was designed to compare the prognosis and fertility outcomes of the patients treated by VRT or ART.
Totally 150 cases, 77 in the VRT and 73 in the ART group, were included. VRT and ART provide similar surgical and pathological outcomes except larger specimens obtained by ART. In the ART group, no patient developed recurrent diseases, but, in the VRT group, 7 (9.8%) patients developed recurrent diseases and 2 (1.6%) patients died of the tumours (P=0.035). The rate of pregnancy in the VRT group was significantly higher than those of ART (39.5% vs 8.8%; P=0.003). The patients with tumour size >2 cm showed significant higher recurrent rate (11.6% vs 2.4%, P<0.05) and lower pregnant rate (12.5% vs 32.1%, P=0.094) compared with the patients with tumour size <2 cm.
Patients treated by ART obtained better oncology results, but their fertility outcomes were unfavourable compared with VRT. Tumour size <2 cm should be emphasised as an indication for radical trachelectomy for improving the outcome of fertility and prognosis.
ABSTRACT
The recent ban on the use of antibiotics as a feed additive has led to the search for alternative sources of antibiotics in the feed industry. Presently, probiotics are considered as a ...potential substitute for antibiotic as a live biotherapeutic agent to improve animal health and performance. Accordingly, study was focused on evaluating the effect of Saccharomyces boulardii (Sb) and Bacillus subtilis B10 (Bs) on ultrastructure modulation and mucosal immunity development in broiler chickens. A total of three hundred 1-d-old Sanhuang broilers (a Chinese cross breed) were randomized into 3 groups, each group with 5 replications (n = 20). The control group (Ctr) was fed a basal diet containing an antibiotic (virginiamycin, 20 mg/kg). Meanwhile, broilers in experimental groups received Sb and Bs (1 × 108 cfu/kg of feed) in addition to the basal diet for 72 d. The results of the experimental groups revealed a significant improvement in live BW and relative weight of bursa of Fabricius and thymus. Also, intestinal villus height, width, and number of goblet cells increased in the Sb and Bs groups. Meanwhile, modulation in the intestinal ultrastructure and increased mRNA expression levels of occluding, cloudin2, and cloudin3 (P < 0.05) were observed in the Sb and Bs groups. Moreover, IgA-positive cells significantly increased in the jejunum of Sb- and Bs-supplemented groups (P < 0.05). Intestinal cytokines interleukin-6, tumor necrosis factor-α, interleukin-10, transforming growth factor-β, and secretory IgA concentrations were (P < 0.05) improved in the probiotic groups; however, Sb induced inflammatory and antiinflammatory cytokines (P < 0.05) in comparison with the Ctr group. The present findings conclusively revealed that Sb and Bs increased IgA-positive cells in the lumen of the intestinal villus and revealed that Sb and Bs could modulate intestinal ultrastructure through increasing occluding, cloudin2, and cloudin3 mRNA expression levels in broiler intestine.
Intracortical microelectrode arrays, especially the Utah array, remain the most common choice for obtaining high dimensional recordings of spiking neural activity for brain computer interface and ...basic neuroscience research. Despite the widespread use and established design, mechanical, material and biological challenges persist that contribute to a steady decline in recording performance (as evidenced by both diminished signal amplitude and recorded cell population over time) or outright array failure. Device implantation injury causes acute cell death and activation of inflammatory microglia and astrocytes that leads to a chronic neurodegeneration and inflammatory glial aggregation around the electrode shanks and often times fibrous tissue growth above the pia along the bed of the array within the meninges. This multifaceted deleterious cascade can result in substantial variability in performance even under the same experimental conditions. We track both impedance signatures and electrophysiological performance of 4 × 4 floating microelectrode Utah arrays implanted in the primary monocular visual cortex (V1m) of Long-Evans rats over a 12-week period. We employ a repeatable visual stimulation method to compare signal-to-noise ratio as well as single- and multi-unit yield from weekly recordings. To explain signal variability with biological response, we compare arrays categorized as either Type 1, partial fibrous encapsulation, or Type 2, complete fibrous encapsulation and demonstrate performance and impedance signatures unique to encapsulation type. We additionally assess benefits of a biomolecule coating intended to minimize distance to recordable units and observe a temporary improvement on multi-unit recording yield and single-unit amplitude.
Abstract Intracortical neural probes enable researchers to measure electrical and chemical signals in the brain. However, penetration injury from probe insertion into living brain tissue leads to an ...inflammatory tissue response. In turn, microglia are activated, which leads to encapsulation of the probe and release of pro-inflammatory cytokines. This inflammatory tissue response alters the electrical and chemical microenvironment surrounding the implanted probe, which may in turn interfere with signal acquisition. Dexamethasone (Dex), a potent anti-inflammatory steroid, can be used to prevent and diminish tissue disruptions caused by probe implantation. Herein, we report retrodialysis administration of dexamethasone while using in vivo two-photon microscopy to observe real-time microglial reaction to the implanted probe. Microdialysis probes under artificial cerebrospinal fluid (aCSF) perfusion with or without Dex were implanted into the cortex of transgenic mice that express GFP in microglia under the CX3CR1 promoter and imaged for 6 h. Acute morphological changes in microglia were evident around the microdialysis probe. The radius of microglia activation was 177.1 μm with aCSF control compared to 93.0 μm with Dex perfusion. T-stage morphology and microglia directionality indices were also used to quantify the microglial response to implanted probes as a function of distance. Dexamethasone had a profound effect on the microglia morphology and reduced the acute activation of these cells.
Abstract Chronic implantation of microelectrodes into the cortex has been shown to lead to inflammatory gliosis and neuronal loss in the microenvironment immediately surrounding the probe, a ...hypothesized cause of neural recording failure. Caspase-1 (aka Interleukin 1β converting enzyme) is known to play a key role in both inflammation and programmed cell death, particularly in stroke and neurodegenerative diseases. Caspase-1 knockout (KO) mice are resistant to apoptosis and these mice have preserved neurologic function by reducing ischemia-induced brain injury in stroke models. Local ischemic injury can occur following neural probe insertion and thus in this study we investigated the hypothesis that caspase-1 KO mice would have less ischemic injury surrounding the neural probe. In this study, caspase-1 KO mice were implanted with chronic single shank 3 mm Michigan probes into V1m cortex. Electrophysiology recording showed significantly improved single-unit recording performance (yield and signal to noise ratio) of caspase-1 KO mice compared to wild type C57B6 (WT) mice over the course of up to 6 months for the majority of the depth. The higher yield is supported by the improved neuronal survival in the caspase-1 KO mice. Impedance fluctuates over time but appears to be steadier in the caspase-1 KO especially at longer time points, suggesting milder glia scarring. These findings show that caspase-1 is a promising target for pharmacologic interventions.
A 28-d experiment was conducted to investigate the effects of feed-conditioning temperature on the pellet quality, growth performance, intestinal development, and blood parameters of geese. A total ...of 180 one-day-old White Yuzhou goslings were randomly allotted to 5 treatment groups, with 6 replicates containing 6 birds each. Five diets were conditioned at 65, 70, 75, 80, and 85°C. Body weight and feed intake per pen basis were recorded from the arrival to the end of the trial. Blood and small intestine samples were collected on d 28 for analysis. The results showed that the pellet durability index (PDI), pellet hardness, and gelatinisation degree of starch (GDS) increased with increasing conditioning temperature (P < 0.05). The final body weight (FBW), average daily gain (ADG) and average daily feed intake (ADFI) of goslings significantly increased when conditioning temperature increased from 65 or 70°C to 80 or 85°C (P < 0.05), accompanied by unaffected feed conversion ratio (FCR) (P > 0.05). The villus height to crypt depth ratio (VH/CD) in the duodenum and ileum improved with increasing conditioning temperature (P < 0.05). Additionally, trypsin and amylase activity were enhanced when the conditioning temperature increased from 65 to 85°C (P < 0.05). No significant differences in the carcass traits and blood parameters of goslings were observed among the groups (P > 0.05). Overall, under the present experimental conditions, increasing the steam-conditioning temperature of pelleted feed improved pellet quality, growth performance, intestinal morphology, and digestive enzyme activity in goslings. Based on broken-line regression analysis, the lower critical conditioning temperature for ADG in geese from 1 to 28 d of age was 80.95°C.
Implantable neural electrode devices are important tools for neuroscience research and have an increasing range of clinical applications. However, the intricacies of the biological response after ...implantation, and their ultimate impact on recording performance, remain challenging to elucidate. Establishing a relationship between the neurobiology and chronic recording performance is confounded by technical challenges related to traditional electrophysiological, material, and histological limitations. This can greatly impact the interpretations of results pertaining to device performance and tissue health surrounding the implant.
In this work, electrophysiological activity and immunohistological analysis are compared after controlling for motion artifacts, quiescent neuronal activity, and material failure of devices in order to better understand the relationship between histology and electrophysiological outcomes.
Even after carefully accounting for these factors, the presence of viable neurons and lack of glial scarring does not convey single unit recording performance.
To better understand the biological factors influencing neural activity, detailed cellular and molecular tissue responses were examined. Decreases in neural activity and blood oxygenation in the tissue surrounding the implant, shift in expression levels of vesicular transporter proteins and ion channels, axon and myelin injury, and interrupted blood flow in nearby capillaries can impact neural activity around implanted neural interfaces. Combined, these tissue changes highlight the need for more comprehensive, basic science research to elucidate the relationship between biology and chronic electrophysiology performance in order to advance neural technologies.
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Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through ...stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants.
One critical challenge to the translation of neural recording/stimulation electrode technology to clinically viable devices for brain computer interface (BCI) or deep brain stimulation (DBS) applications is the chronic degradation of device performance due to the inflammatory tissue reaction. While many hypothesize that soft and flexible devices elicit reduced inflammatory tissue responses, there has yet to be a rigorous comparison between soft and stiff implants. We have developed an ultra-soft microelectrode with Young’s modulus lower than 1MPa, closely mimicking the brain tissue modulus. Here, we present a rigorous histological comparison of this novel ultrasoft electrode and conventional stiff electrode with the same size, shape and surface chemistry, implanted in rat brains for 1-week and 8-weeks. Significant improvement was observed for ultrasoft electrodes, including inflammatory tissue reaction, electrode-tissue integration as well as mechanical disturbance to nearby neurons. A full spectrum of new techniques were developed in this study, from insertion shuttle to in situ sectioning of the microelectrode to automated cell shape analysis, all of which should contribute new methods to the field. Finally, we showed the electrical functionality of the ultrasoft electrode, demonstrating the potential of flexible neural implant devices for future research and clinical use.
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