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1.
Opt Express ; 32(12): 20459-20470, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38859427

ABSTRACT

When a hollow core fiber is drawn, the core and cladding holes within the internal cane geometry are pressurized with an inert gas to enable precise control over the internal microstructure of the fiber and counteract surface tension forces. Primarily by considering the temperature drop as the fiber passes through the furnace and the geometrical transformation of the internal microstructure from preform-to-fiber, we recently established that the gas pressure within the final 'as-drawn' fiber is substantially below atmospheric pressure. We have also established that slight changes in the gas refractive index within the core and surrounding cladding holes induced by changes in gas pressure are sufficient to significantly affect both the modality and loss of the fiber. Here we demonstrate, through both simulations and experimental measurements, that the combination of these effects leads to transient changes in the fiber's attenuation when the fibers are opened to atmosphere post-fabrication. It is important to account for this phenomenon for accurate fiber characterization, particularly when long lengths of fiber are drawn where it could take many weeks for every part of the internal microstructure to reach atmospheric pressure.

2.
Sensors (Basel) ; 24(8)2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38676099

ABSTRACT

Label-free and multiphoton micro-endoscopy can transform clinical histopathology by providing an in situ tool for diagnostic imaging and surgical treatment in diseases such as cancer. Key to a multiphoton imaging-based micro-endoscopic device is the optical fiber, for distortion-free and efficient delivery of ultra-short laser pulses to the sample and effective signal collection. In this work, we study a new hollow-core (air-filled) double-clad anti-resonant fiber (DC-ARF) as a high-performance candidate for multiphoton micro-endoscopy. We compare the fiber characteristics of the DC-ARF with a single-clad anti-resonant fiber (SC-ARF) and a solid core fiber (SCF). In this work, while the DC-ARF and the SC-ARF enable low-loss (<0.2 dBm-1), close to dispersion-free excitation pulse delivery (<10% pulse width increase at 900 nm per 1 m fiber) without any induced non-linearities, the SCF resulted in spectral broadening and pulse-stretching (>2000% of pulse width increase at 900 nm per 1 m fiber). An ideal optical fiber endoscope needs to be several meters long and should enable both excitation and collection through the fiber. Therefore, we performed multiphoton imaging on endoscopy-compatible 1 m and 3 m lengths of fiber in the back-scattered geometry, wherein the signals were collected either directly (non-descanned detection) or through the fiber (descanned detection). Second harmonic images were collected from barium titanate crystals as well as from biological samples (mouse tail tendon). In non-descanned detection conditions, the ARFs outperformed the SCF by up to 10 times in terms of signal-to-noise ratio of images. Significantly, only the DC-ARF, due to its high numerical aperture (NA) of 0.45 and wide-collection bandwidth (>1 µm), could provide images in the de-scanned detection configuration desirable for endoscopy. Thus, our systematic characterization and comparison of different optical fibers under different image collection configurations, confirms and establishes the utility of DC-ARFs for high-performing label-free multiphoton imaging-based micro-endoscopy.

3.
Opt Lett ; 48(23): 6224-6227, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38039232

ABSTRACT

This Letter reports the first, to the best of our knowledge, spectral radiation induced attenuation (RIA) measurements of nested anti-resonant nodeless hollow-core fibers (NANFs). A 5-tube NANF, alongside a solid-core single-mode radiation resistant fiber (SM-RRF), was irradiated under γ-ray up to 101 kGy (SiO2) and under x-ray up to 241 kGy (SiO2). No RIA was observed in the NANF in the second half of the O-band, the S-band, the C-band, and the L-band. The NANF showed a reduction of absorption bands associated with water and HCl under irradiation. Three new attenuation peaks were radiolytically induced and are attributed to the creation of HNO3. These peaks are centered respectively at 1441 nm, 1532 nm, and 1628 nm, with a full width at half maximum (FWHM) of, respectively, 10 nm, 12 nm, and 12 nm. These results demonstrate that the wide bandwidth range of NANFs is essentially unaffected by radiation, but the internal gas contents of the NANF must be managed to avoid producing undesirable spectral features through radiolytic reactions. Wide spectral regions almost unaffected by the ionizing radiation could open new possibilities for the use of NANF in harsh radiation environments.

4.
Opt Express ; 31(21): 34064-34073, 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37859171

ABSTRACT

By exploiting the excellent short-term phase stability between consecutive pulses from a free-running optical parametric oscillator frequency comb, we report the first example of hollow-core fiber-delivered heterodyne spectroscopy in the 3.1-3.8 µm wavelength range. The technique provides a means of spectroscopically interrogating a sample situated at the distal end of a fiber, with all electronics and light sources situated at the proximal end and with an inherent capability to suppress spectroscopically interfering features present in the free-space and in-fiber delivery path. Using a silica anti-resonant, hollow-core delivery fiber, we demonstrate high quality transmission and attenuated total reflectance spectroscopy of a plastic sample for fiber lengths of up to 40 m, significantly exceeding the few-meter lengths typically possible using solid-core fibers. The technique opens a route to implementing multi-species spectroscopic monitoring in remote and / or hostile industrial environments and medical applications.

5.
J Pers Soc Psychol ; 125(6): 1265-1307, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37796593

ABSTRACT

Many college students, especially first-generation and underrepresented racial/ethnic minority students, desire courses and careers that emphasize helping people and society. Can instructors of introductory science, technology, engineering, and math (STEM) courses promote motivation, performance, and equity in STEM fields by emphasizing the prosocial relevance of course material? We developed, implemented, and evaluated a prosocial utility-value intervention (UVI): A course assignment in which students were asked to reflect on the prosocial value of biology or chemistry course content; our focus was on reducing performance gaps between first-generation and continuing generation college students. In Studies 1a and 1b, we piloted two versions of a prosocial UVI in introductory biology (N = 282) and chemistry classes (N = 1,705) to test whether we could encourage students to write about the prosocial value of course content. In Study 2, we tested a version of the UVI that combines personal and prosocial values, relative to a standard UVI, which emphasizes personal values, using a randomized controlled trial in an introductory chemistry course (N = 2,505), and examined effects on performance and motivation in the course. In Study 3, we tested the prosocial UVI against a standard UVI in an introductory biology course (N = 712). Results suggest that the prosocial UVI may be particularly effective in promoting motivation and performance for first-generation college students, especially those who are more confident that they can perform well in the class, reflecting a classic expectancy-value interaction. Mediation analyses suggest that this intervention worked by promoting interest in chemistry. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Ethnicity , Minority Groups , Humans , Engineering/education , Technology/education , Students
6.
Opt Express ; 30(24): 43317-43329, 2022 Nov 21.
Article in English | MEDLINE | ID: mdl-36523032

ABSTRACT

We demonstrate recent progress in the development of a Raman gas sensor using a single cladding ring anti-resonant hollow core micro-structured optical fiber (HC-ARF) and a low power pump source. The HC-ARF was designed specifically for low attenuation and wide bandwidth in the visible spectral region and provided low loss at both the pump wavelength (532 nm) and Stokes wavelengths up to a Raman shift of 5000 cm-1. A novel selective core pressurization scheme was also implemented to further reduce the confinement loss, improving the Raman signal enhancement by a factor of 1.9 compared to a standard fiber filling scheme. By exploiting longer lengths of fiber, direct detection of both methane and hydrogen at concentrations of 5 and 10 ppm respectively is demonstrated and a noise equivalent limit-of-detection of 0.15 ppm is calculated for methane.

7.
Opt Lett ; 47(20): 5301-5304, 2022 Oct 15.
Article in English | MEDLINE | ID: mdl-36240347

ABSTRACT

We report a high-power single-mode mid-infrared (MIR) pulse delivery system via anti-resonant hollow-core fiber (HCF) with a record delivery distance of 108 m. Near-diffraction-limited MIR light was transmitted by HCFs at wavelengths of 3.12-3.58 µm using a tunable optical parametric oscillator (OPO) as the light source. The HCFs were purged beforehand with argon in order to remove or reduce loss due to parasitic gas absorption (HCl, CO2, etc.). The minimum fiber loss values were 0.05 and 0.24 dB/m at 3.4-3.6 µm and 4.5-4.6 µm, respectively, with the 4.5-4.6 µm loss figure representing, to the best of our knowledge, a new low loss record for a HCF in this spectral region. At a coupling efficiency of ∼70%, average powers of 592 mW and 133 mW were delivered through 5 m and 108 m of HCF, respectively. Assuming the 120-ps duration of the MIR pulses remained constant over the low-dispersion HCF (theoretical maximum: 0.4 ps/nm/km), the corresponding calculated peak powers were 4.9 kW and 1.1 kW.

8.
Nat Commun ; 13(1): 4139, 2022 Jul 16.
Article in English | MEDLINE | ID: mdl-35842421

ABSTRACT

Today's optical communication systems are fast approaching their capacity limits in the conventional telecom bands. Opening up new wavelength bands is becoming an appealing solution to the capacity crunch. However, this ordinarily requires the development of optical transceivers for any new wavelength band, which is time-consuming and expensive. Here, we present an on-chip continuous spectral translation method that leverages existing commercial transceivers to unlock the vast and currently unused potential new wavelength bands. The spectral translators are continuous-wave laser pumped aluminum gallium arsenide on insulator (AlGaAsOI) nanowaveguides that provide a continuous conversion bandwidth over an octave. We demonstrate coherent transmission in the 2-µm band using well-developed conventional C-band transmitters and coherent receivers, as an example of the potential of the spectral translators that could also unlock communications at other wavelength bands. We demonstrate 318.25-Gbit s-1 Nyquist wavelength-division multiplexed coherent transmission over a 1.15-km hollow-core fibre using this approach. Our demonstration paves the way for transmitting, detecting, and processing signals at wavelength bands beyond the capability of today's devices.

9.
Opt Express ; 30(5): 7044-7052, 2022 Feb 28.
Article in English | MEDLINE | ID: mdl-35299476

ABSTRACT

High-resolution multi-species spectroscopy is achieved by delivering broadband 3-4-µm mid-infrared light through a 4.5-meter-long silica-based hollow-core optical fiber. Absorptions from H37Cl, H35Cl, H2O and CH4 present in the gas within the fiber core are observed, and the corresponding gas concentrations are obtained to 5-ppb precision using a high-resolution Fourier-transform spectrometer and a full-spectrum multi-species fitting algorithm. We show that by fully fitting the narrow absorption features of these light molecules their contributions can be nulled, enabling further spectroscopy of C3H6O and C3H8O contained in a Herriott cell after the fiber. As a demonstration of the potential to extend fiber-delivered broadband mid-infrared spectroscopy to significant distances, we present a high-resolution characterization of the transmission of a 63-meter length of hollow-core fiber, fully fitting the input and output spectra to obtain the intra-fiber gas concentrations. We show that, despite the fiber not having been purged, useful spectroscopic windows are still preserved which have the potential to enable hydrocarbon spectroscopy at the distal end of fibers with lengths of tens or even hundreds of meters.

11.
JMIR Res Protoc ; 11(1): e30186, 2022 Jan 14.
Article in English | MEDLINE | ID: mdl-35029534

ABSTRACT

BACKGROUND: Alcohol use disorder is a chronic disorder with a high likelihood of relapse. The consistent monitoring of blood alcohol concentration through breathalyzers is critical to identifying relapse or misuse. Smartphone apps as a replacement of or in conjunction with breathalyzers have shown limited effectiveness. Yet, there has been little research that has effectively utilized wireless or Wi-Fi-enabled breathalyzers that can accurately, securely, and reliably measure blood alcohol concentration. OBJECTIVE: The purpose of this study is to evaluate the impact of a wireless blood alcohol concentration device in collaboration with long-term treatment on dropout rates, psychological distress, treatment motivation, quality of life, and need for higher levels of follow-up care for patients with alcohol use disorder. METHODS: The randomized clinical trial will include two arms, access to the wireless breathalyzer versus no access to the breathalyzer, while both groups have access to treatment. Evaluation will last 3 months with a 6-week follow-up, during which each participant will be interviewed at admission, 1 month in, 2 months in, 3 months in, and follow-up. Individuals will be recruited online through a secure telehealth meeting invitation. Outcomes will focus on the impact of the wireless breathalyzer within the alcohol use disorder population, and the combined effect on psychological distress, treatment motivation, and quality of life. In addition, we intend to investigate the impact of the breathalyzer on dropout rates and participants' need for higher levels of follow-up care and treatment. RESULTS: The recruitment of this study started in July 2020 and will run until 2022. CONCLUSIONS: This information will be important to develop cost-effective treatments for alcohol dependence. Ongoing monitoring allows treatment providers to take an individualized disease management approach and facilitates timely intervention by the treatment provider. TRIAL REGISTRATION: ClinicalTrials.gov NCT04380116; http://clinicaltrials.gov/ct2/show/NCT04380116. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30186.

12.
Alzheimers Res Ther ; 13(1): 192, 2021 12 06.
Article in English | MEDLINE | ID: mdl-34872596

ABSTRACT

BACKGROUND: Significant cognitive changes as individuals' age are not being identified in a timely manner, delaying diagnosis and treatments. Use of brief, multi-domain, self-administered, objective cognitive assessment tools may remove some barriers in assessing and identifying cognitive changes. We compared longitudinal Self-Administered Gerocognitive Examination (SAGE) test scores to non-self-administered Mini-Mental State Examination (MMSE) scores in 5 different diagnostic subgroups. METHODS: A cohort study evaluating annual rates of change was performed on 665 consecutive patients from Ohio State University Memory Disorders Clinic. Patients with at least two visits 6 months apart evaluated with SAGE and MMSE and classified according to standard clinical criteria as subjective cognitive decline (SCD), mild cognitive impairment (MCI), or Alzheimer's disease (AD) dementia were included. The pattern of change in SAGE scores was compared to MMSE. One way and repeated measures ANOVA and linear regression models were used. RESULTS: Four hundred twenty-four individuals (40 SCD, 94 MCI non-converters to dementia, 70 MCI converters to dementia (49 to AD dementia and 21 to non-AD dementia), 220 AD dementia) met inclusion criteria. SAGE and MMSE scores declined respectively at annual rates of 1.91 points/year (p < 0.0001) and 1.68 points/year (p < 0.0001) for MCI converters to AD dementia, and 1.82 points/year (p < 0.0001) and 2.38 points/year (p < 0.0001) for AD dementia subjects. SAGE and MMSE scores remained stable for SCD and MCI non-converters. Statistically significant decline from baseline scores in SAGE occurred at least 6 months earlier than MMSE for MCI converters to AD dementia (14.4 vs. 20.4 months), MCI converters to non-AD dementia (14.4 vs. 32.9 months), and AD dementia individuals (8.3 vs. 14.4 months). CONCLUSIONS: SAGE detects MCI conversion to dementia at least 6 months sooner than MMSE. Being self-administered, SAGE also addresses a critical need of removing some barriers in performing cognitive assessments. Limitations of our single-site cohort study include potential referral and sampling biases. Repetitively administering SAGE and identifying stability or decline may provide clinicians with an objective cognitive biomarker impacting evaluation and management choices.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Cohort Studies , Disease Progression , Humans , Mental Status and Dementia Tests , Neuropsychological Tests
13.
Opt Express ; 28(11): 16542-16553, 2020 May 25.
Article in English | MEDLINE | ID: mdl-32549474

ABSTRACT

We report the first extruded tellurite antiresonant hollow core fibers (HC-ARFs) aimed at the delivery of mid-infrared (Mid-IR) laser radiation. The preform extrusion fabrication process allowed us to obtain preforms with non-touching capillaries in a single step, hence minimizing thermal cycles. The fibers were fabricated from in-house synthetized tellurite glass (containing Zn, Ba and K oxides) and co-drawn with a fluorinated ethylene propylene (FEP) polymer outer layer to improve their mechanical properties and protect the glass from humidity. The fabricated HC-ARFs transmit in the Mid-IR spectral range from 4.9 to 6 µm. We measured losses of ∼8.2, 4.8 and 6.4 dB/m at 5 µm, 5.6 µm and 5.8 µm, respectively in two different fibers. These losses, which are dominated by leakage mostly arising from a non-uniform membrane thickness, represent the lowest attenuation reported for a tellurite-based HC-ARF to date. The fibers present good beam quality and an M2 factor of 1.2. Modelling suggests that by improving the uniformity in the capillary membrane thickness losses down to 0.05 dB/m at 5.4 µm should be possible, making this solution attractive, for example, for beam delivery from a CO laser.

14.
Opt Express ; 27(15): 20567-20582, 2019 Jul 22.
Article in English | MEDLINE | ID: mdl-31510148

ABSTRACT

The fabrication of hollow core microstructured fibers is significantly more complex than solid fibers due to the necessity to control the hollow microstructure with high precision during the draw. We present the first model that can recreate tubular anti-resonant hollow core fiber draws, and accurately predict the draw parameters and geometry of the fiber. The model was validated against two different experimental fiber draws and very good agreement was found. We identify a dynamic within the draw process that can lead to a premature and irreversible contact between neighboring capillaries inside the hot zone, and describe mitigating strategies. We then use the model to explore the tolerance of the draw process to unavoidable structural variations within the preform, and to study feasibility and limiting phenomena of increasing the produced yield. We discover that the aspect ratio of the capillaries used in the preform has a direct effect on the uniformity of drawn fibers. Starting from high precision preforms the model predicts that it could be possible to draw 100 km of fiber from a single meter of preform.

15.
Opt Express ; 26(22): 28621-28633, 2018 Oct 29.
Article in English | MEDLINE | ID: mdl-30470035

ABSTRACT

We describe a compact, all fiber, frequency stabilized diode laser system at 2051 nm using CO2 gas-filled Kagome Hollow Core Fiber (HCF), capable of tuning continuously over four transitions in 12C16O2: R(24), R(26), R(28), and R(30). This laser system has been designed for use in future space-based atmospheric monitoring using differential absorption lidar (DIAL). The fully spliced Kagome HCF gas cell is filled to 2 kPa CO2 partial pressure and we compare the observed CO2 lineshape features with those calculated using HITRAN, to quantify the properties of the CO2-filled fiber cell. In this first demonstration of Kagome HCF used in a fully sealed gas cell configuration for spectroscopy at 2 µm, we characterize the frequency stability of the locked system by beat frequency comparison against a reference laser. Results are presented for the laser locked to the center of the 12C16O2 R(30) transition, with frequency stability of ∼40 kHz or better at 1 s, and a frequency reproducibility at the 0.4-MHz level over a period of > 1 month. For DIAL applications, we also demonstrate two methods of stabilizing the laser frequency ~3 GHz from this line. Furthermore, no pressure degradation was observed during the ~15-month period in which frequency stability measurements were acquired.

16.
Semin Neurol ; 38(5): 515-521, 2018 10.
Article in English | MEDLINE | ID: mdl-30321889

ABSTRACT

There are ethical aspects to each of the three phases of cerebrovascular disease: hyperacute management, acute prognostication and management of early complications, and long-term recovery and reintegration with the community. This article addresses ethical concerns pertinent to each phase. First, we discuss ethical issues regarding consent for thrombolysis and endovascular treatment for acute ischemic stroke, including a review of considerations regarding the provision of acute stroke treatment advice over the telephone. Next, we discuss capacity for consent and prognostication after ischemic stroke and intracranial hemorrhage, with a focus on the problems of the self-fulfilling prophecy. Finally, we discuss residual disability and patients' return to driving. Consideration of these ethical dimensions of cerebrovascular disease will assist neurologists in caring for patients and families suffering from this complex condition.


Subject(s)
Consent Forms/ethics , Fibrinolytic Agents/therapeutic use , Neurology/ethics , Stroke/therapy , Thrombolytic Therapy/ethics , Humans , Physicians/ethics
17.
Opt Express ; 26(7): 8866-8882, 2018 Apr 02.
Article in English | MEDLINE | ID: mdl-29715848

ABSTRACT

Atmospheric air-filled hollow core (HC) fibers, representing the simplest yet reliable form of gas-filled hollow core fiber, show remarkable nonlinear properties and have several interesting applications such as pulse compression, frequency conversion and supercontinuum generation. Although the propagation of sub-picosecond and few hundred picosecond pulses are well-studied in air-filled fibers, the nonlinear response of air to pulses with a duration of a few picoseconds has interesting features that have not yet been explored fully. Here, we experimentally and theoretically study the nonlinear propagation of ~6 ps pulses in three different types of atmospheric air-filled HC fiber. With this pulse length, we were able to explore different nonlinear characteristics of air at different power levels. Using in-house-fabricated, state-of-the-art HC photonic bandgap, HC tubular and HC Kagomé fibers, we were able to associate the origin of the initial pulse broadening process in these fibers to rotational Raman scattering (RRS) at low power levels. Due to the broadband and low loss transmission window of the HC Kagomé fiber we used, we observed the transition from initial pulse broadening (by RRS) at lower powers, through long-range frequency conversion (2330 cm-1) with the help of vibrational Raman scattering, to broadband (~700 nm) supercontinuum generation at high power levels. To model such a wide range of nonlinear processes in a unified approach, we have implemented a semi-quantum model for air into the generalized nonlinear Schrodinger equation, which surpasses the limits of the common single damping oscillator model in this pulse length regime. The model has been validated by comparison with experimental results and provides a powerful tool for the design, modeling and optimization of nonlinear processes in air-filled HC fibers.

18.
Health Promot Pract ; 19(4): 495-505, 2018 07.
Article in English | MEDLINE | ID: mdl-28583024

ABSTRACT

Innovative strategies are needed to reduce the hypertension epidemic among African Americans. Reach Out was a faith-collaborative, mobile health, randomized, pilot intervention trial of four mobile health components to reduce high blood pressure (BP) compared to usual care. It was designed and tested within a community-based participatory research framework among African Americans recruited and randomized from churches in Flint, Michigan. The purpose of this pilot study was to assess the feasibility of the Reach Out processes. Feasibility was assessed by willingness to consent (acceptance of randomization), proportion of weeks participants texted their BP readings (intervention use), number lost to follow-up (retention), and responses to postintervention surveys and focus groups (acceptance of intervention). Of the 425 church members who underwent BP screening, 94 enrolled in the study and 73 (78%) completed the 6-month outcome assessment. Median age was 58 years, and 79% were women. Participants responded with their BPs on an average of 13.7 (SD = 10.7) weeks out of 26 weeks that the BP prompts were sent. All participants reported satisfaction with the intervention. Reach Out, a faith-collaborative, mobile health intervention was feasible. Further study of the efficacy of the intervention and additional mobile health strategies should be considered.


Subject(s)
Black or African American/statistics & numerical data , Community-Based Participatory Research/methods , Health Promotion/methods , Hypertension/prevention & control , Telemedicine/methods , Adult , Blood Pressure , Feasibility Studies , Female , Humans , Hypertension/ethnology , Male , Michigan , Middle Aged , Pilot Projects , Surveys and Questionnaires
19.
J Neuroinflammation ; 14(1): 162, 2017 08 18.
Article in English | MEDLINE | ID: mdl-28821276

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease classically associated with axonal damage and loss; more recently, however, synaptic changes have been recognized as additional contributing factors. An anatomical area commonly affected in MS is the visual pathway; yet, changes other than those associated with inflammatory demyelination of the optic nerve, i.e., optic neuritis, have not been described in detail. METHODS: Adult mice were subjected to a diet containing cuprizone to mimic certain aspects of inflammatory demyelination as seen in MS. Demyelination and inflammation were assessed by real-time polymerase chain reaction and immunohistochemistry. Synaptic changes associated with inflammatory demyelination in the dorsal lateral geniculate nucleus (dLGN) were determined by immunohistochemistry, Western blot analysis, and electrophysiological field potential recordings. RESULTS: In the cuprizone model, demyelination was observed in retinorecipient regions of the subcortical visual system, in particular the dLGN, where it was found accompanied by microglia activation and astrogliosis. In contrast, anterior parts of the pathway, i.e., the optic nerve and tract, appeared largely unaffected. Under the inflammatory demyelinating conditions, as seen in the dLGN of cuprizone-treated mice, there was an overall decrease in excitatory synaptic inputs from retinal ganglion cells. At the same time, the number of synaptic complexes arising from gamma-aminobutyric acid (GABA)-generating inhibitory neurons was found increased, as were the synapses that contain the N-methyl-D-aspartate receptor (NMDAR) subunit GluN2B and converge onto inhibitory neurons. These synaptic changes were functionally found associated with a shift toward an overall increase in network inhibition. CONCLUSIONS: Using the cuprizone model of inflammatory demyelination, our data reveal a novel form of synaptic (mal)adaption in the CNS that is characterized by a shift of the excitation/inhibition balance toward inhibitory network activity associated with an increase in GABAergic inhibitory synapses and a possible increase in excitatory input onto inhibitory interneurons. In addition, our data recognize the cuprizone model as a suitable tool in which to assess the effects of inflammatory demyelination on subcortical retinorecipient regions of the visual system, such as the dLGN, in the absence of overt optic neuritis.


Subject(s)
Cuprizone/toxicity , Demyelinating Diseases/chemically induced , Demyelinating Diseases/pathology , Geniculate Bodies/pathology , Visual Pathways/pathology , Animals , Chelating Agents/toxicity , Corpus Callosum/drug effects , Corpus Callosum/pathology , Geniculate Bodies/drug effects , Male , Mice , Mice, Inbred C57BL , Visual Pathways/drug effects
20.
ASN Neuro ; 8(5)2016 Oct.
Article in English | MEDLINE | ID: mdl-27659560

ABSTRACT

White matter injury has been frequently reported in HIV+ patients. Previous studies showed that HIV-1 Tat (transactivator of transcription), a viral protein that is produced and secreted by HIV-infected cells, is toxic to young, immature oligodendrocytes (OLGs). Adding Tat to the culture medium reduced the viability of immature OLGs, and the surviving OLGs exhibited reduced process networks. OLGs produce and secrete autotaxin (ATX), an ecto-enzyme containing a lysophospholipase D (lysoPLD) activity that converts lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a lipid signaling molecule that stimulates OLG differentiation. We hypothesized that Tat affects OLG development by interfering with the ATX-LPA signaling pathway. Our data show that Tat treatment leads to changes in the expression of OLG differentiation genes and the area of OLG process networks, both of which can be rescued by LPA. Tat-treated OLGs showed no change in LPA receptor expression but significantly decreased extracellular ATX levels and lysoPLD activity. In Tat transgenic mice, expression of Tat in vivo leads to decreased OLG ATX secretion. Furthermore, co-immunoprecipitation experiments revealed a potential physical interaction between Tat and ATX. Together, these data strongly suggest two functional implications of Tat blocking ATX's lysoPLD activity. On one hand, it attenuates OLG differentiation, and on the other hand it interferes with the protective effects of LPA on OLG process morphology.

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