scholarly journals Hippocampal neurons respond to brain activity with functional hypoxia

2021 ◽  
Author(s):  
Umer Javed Butt ◽  
Agnes A. Steixner-Kumar ◽  
Constanze Depp ◽  
Ting Sun ◽  
Imam Hassouna ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Brain Activity ◽  
Well Being ◽  
Light Sheet ◽  
Positive Control ◽  
Light Sheet Microscopy ◽  
Non Invasive ◽  
Complex Motor ◽  
Cognitive Challenge ◽  
Global Brain

AbstractPhysical activity and cognitive challenge are established non-invasive methods to induce comprehensive brain activation and thereby improve global brain function including mood and emotional well-being in healthy subjects and in patients. However, the mechanisms underlying this experimental and clinical observation and broadly exploited therapeutic tool are still widely obscure. Here we show in the behaving brain that physiological (endogenous) hypoxia is likely a respective lead mechanism, regulating hippocampal plasticity via adaptive gene expression. A refined transgenic approach in mice, utilizing the oxygen-dependent degradation (ODD) domain of HIF-1α fused to CreERT2 recombinase, allows us to demonstrate hypoxic cells in the performing brain under normoxia and motor-cognitive challenge, and spatially map them by light-sheet microscopy, all in comparison to inspiratory hypoxia as strong positive control. We report that a complex motor-cognitive challenge causes hypoxia across essentially all brain areas, with hypoxic neurons particularly abundant in the hippocampus. These data suggest an intriguing model of neuroplasticity, in which a specific task-associated neuronal activity triggers mild hypoxia as a local neuron-specific as well as a brain-wide response, comprising indirectly activated neurons and non-neuronal cells.

scholarly journals DSS-induced inflammation in the colon drives a pro-inflammatory signature in the brain that is ameliorated by prophylactic treatment with the S100A9 inhibitor paquinimod

2021 ◽  
Author(s):  
Sarah Talley ◽  
Rasa Valiauga ◽  
Lillian Anderson ◽  
Abigail R Cannon ◽  
Mashkoor A Choudhry ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Inflammatory Cytokines ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Light Sheet ◽  
Positive Control ◽  
Light Sheet Microscopy ◽  
Cytokines And Chemokines ◽  
Organ Systems ◽  
The Brain

Background: Inflammatory Bowel Disease (IBD) is established to drive pathological sequelae in organ systems outside the intestine, including the central nervous system (CNS). Many patients exhibit cognitive deficits, particularly during disease flare. The connection between colonic inflammation and neuroinflammation remains unclear and characterization of the neuroinflammatory phenotype in the brain during colitis is ill-defined. Methods: Transgenic mice expressing a bioluminescent reporter of active caspase-1 were treated with 2% Dextran Sodium Sulfate (DSS) for 7 days to induce acute colitis, and colonic, systemic and neuroinflammation were assessed. In some experiments, mice were prophylactically treated with paquinimod (ABR-215757) to inhibit S100A9 inflammatory signaling. As a positive control for peripheral-induced neuroinflammation, mice were injected with lipopolysaccharide (LPS). Colonic, systemic and brain inflammatory cytokines and chemokines were measured by cytokine bead array (CBA) and Proteome profiler mouse cytokine array. Bioluminescence was quantified in the brain and caspase activation was confirmed by immunoblot. Immune cell infiltration into the CNS was measured by flow cytometry, while light sheet microscopy was used to monitor changes in resident microglia localization in intact brains during DSS or LPS-induced neuroinflammation. RNA sequencing was performed to identify transcriptomic changes occurring in the CNS of DSS-treated mice. Expression of inflammatory biomarkers were quantified in the brain and serum by qRT-PCR, ELISA and WB. Results: DSS-treated mice exhibited clinical hallmarks of colitis, including weight loss, colonic shortening and inflammation in the colon. We also detected a significant increase in inflammatory cytokines in the serum and brain, as well as caspase and microglia activation in the brain of mice with ongoing colitis. RNA sequencing of brains isolated from DSS-treated mice revealed differential expression of genes involved in the regulation of inflammatory responses. This inflammatory phenotype was similar to the signature detected in LPS-treated mice, albeit less robust and transient, as inflammatory gene expression returned to baseline following cessation of DSS. Pharmacological inhibition of S100A9, one of the transcripts identified by RNA sequencing, attenuated colitis severity and systemic and neuroinflammation. Conclusions: Our findings suggest that local inflammation in the colon drives systemic inflammation and neuroinflammation, and this can be ameliorated by inhibition of the S100 alarmin, S100A9.

scholarly journals Optical Sectioning of Live Mammal with Near-Infrared Light Sheet

2018 ◽  
Author(s):  
Feifei Wang ◽  
Hao Wan ◽  
Jingying Yue ◽  
Mingxi Zhang ◽  
Zhuoran Ma ◽  
...  
Keyword(s):  
Near Infrared ◽  
Optical Excitation ◽  
Light Sheet ◽  
Infrared Light ◽  
Optical Sectioning ◽  
Spatiotemporal Resolution ◽  
Near Infrared Light ◽  
Light Sheet Microscopy ◽  
Non Invasive

AbstractDeep-tissue three-dimensional optical imaging of live mammals in vivo with high spatiotemporal resolution in non-invasive manners has been challenging due to light scattering. Here, we developed near-infrared (NIR) light sheet microscopy (LSM) with optical excitation and emission wavelengths up to ~ 1320 nm and ~ 1700 nm respectively, far into the NIR-II (1000-1700 nm) region for 3D optical sectioning through live tissues. Suppressed scattering of both excitation and emission photons allowed one-photon optical sectioning at ~ 2 mm depth in highly scattering brain tissues. NIR-II LSM enabled non-invasive in vivo imaging of live mice, revealing never-before-seen dynamic processes such as highly abnormal tumor microcirculation, and 3D molecular imaging of an important immune checkpoint protein, programmed-death ligand 1 (PD-L1) receptors at the single cell scale in tumors. In vivo two-color near-infrared light sheet sectioning enabled simultaneous volumetric imaging of tumor vasculatures and PD-L1 proteins in live mammals.

scholarly journals The Applications of Lattice Light-sheet Microscopy for Functional Volumetric Imaging of Hippocampal Neurons in a Three-Dimensional Culture System

Micromachines ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 599 ◽  
Author(s):  
Chen ◽  
Liu ◽  
Lu ◽  
Lee ◽  
Tsai ◽  
...  
Keyword(s):  
Cell Culture ◽  
Hippocampal Neurons ◽  
Three Dimensional ◽  
Light Sheet ◽  
Three Dimensions ◽  
Laser Exposure ◽  
Spatiotemporal Resolution ◽  
Strong Light ◽  
Light Sheet Microscopy ◽  
Volumetric Images

The characterization of individual cells in three-dimensions (3D) with very high spatiotemporal resolution is crucial for the development of organs-on-chips, in which 3D cell cultures are integrated with microfluidic systems. In this study, we report the applications of lattice light-sheet microscopy (LLSM) for monitoring neuronal activity in three-dimensional cell culture. We first established a 3D environment for culturing primary hippocampal neurons by applying a scaffold-based 3D tissue engineering technique. Fully differentiated and mature hippocampal neurons were observed in our system. With LLSM, we were able to monitor the behavior of individual cells in a 3D cell culture, which was very difficult under a conventional microscope due to strong light scattering from thick samples. We demonstrated that our system could study the membrane voltage and intracellular calcium dynamics at subcellular resolution in 3D under both chemical and electrical stimulation. From the volumetric images, it was found that the voltage indicators mainly resided in the cytosol instead of the membrane, which cannot be distinguished using conventional microscopy. Neuronal volumetric images were sheet scanned along the axial direction and recorded at a laser exposure of 6 ms, which covered an area up to 4800 μm2, with an image pixel size of 0.102 μm. When we analyzed the time-lapse volumetric images, we could quantify the voltage responses in different neurites in 3D extensions.

scholarly journals DSS-induced inflammation in the colon drives a proinflammatory signature in the brain that is ameliorated by prophylactic treatment with the S100A9 inhibitor paquinimod

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Sarah Talley ◽  
Rasa Valiauga ◽  
Lillian Anderson ◽  
Abigail R. Cannon ◽  
Mashkoor A. Choudhry ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Inflammatory Cytokines ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Light Sheet ◽  
Positive Control ◽  
Light Sheet Microscopy ◽  
Cytokines And Chemokines ◽  
Organ Systems ◽  
The Brain

Abstract Background Inflammatory bowel disease (IBD) is established to drive pathological sequelae in organ systems outside the intestine, including the central nervous system (CNS). Many patients exhibit cognitive deficits, particularly during disease flare. The connection between colonic inflammation and neuroinflammation remains unclear and characterization of the neuroinflammatory phenotype in the brain during colitis is ill-defined. Methods Transgenic mice expressing a bioluminescent reporter of active caspase-1 were treated with 2% dextran sodium sulfate (DSS) for 7 days to induce acute colitis, and colonic, systemic and neuroinflammation were assessed. In some experiments, mice were prophylactically treated with paquinimod (ABR-215757) to inhibit S100A9 inflammatory signaling. As a positive control for peripheral-induced neuroinflammation, mice were injected with lipopolysaccharide (LPS). Colonic, systemic and brain inflammatory cytokines and chemokines were measured by cytokine bead array (CBA) and Proteome profiler mouse cytokine array. Bioluminescence was quantified in the brain and caspase activation was confirmed by immunoblot. Immune cell infiltration into the CNS was measured by flow cytometry, while light sheet microscopy was used to monitor changes in resident microglia localization in intact brains during DSS or LPS-induced neuroinflammation. RNA sequencing was performed to identify transcriptomic changes occurring in the CNS of DSS-treated mice. Expression of inflammatory biomarkers were quantified in the brain and serum by qRT-PCR, ELISA and WB. Results DSS-treated mice exhibited clinical hallmarks of colitis, including weight loss, colonic shortening and inflammation in the colon. We also detected a significant increase in inflammatory cytokines in the serum and brain, as well as caspase and microglia activation in the brain of mice with ongoing colitis. RNA sequencing of brains isolated from DSS-treated mice revealed differential expression of genes involved in the regulation of inflammatory responses. This inflammatory phenotype was similar to the signature detected in LPS-treated mice, albeit less robust and transient, as inflammatory gene expression returned to baseline following cessation of DSS. Pharmacological inhibition of S100A9, one of the transcripts identified by RNA sequencing, attenuated colitis severity and systemic and neuroinflammation. Conclusions Our findings suggest that local inflammation in the colon drives systemic inflammation and neuroinflammation, and this can be ameliorated by inhibition of the S100 alarmin, S100A9.

scholarly journals Achromatic terahertz Airy beam generation with dielectric metasurfaces

Nanophotonics ◽  
2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Qingqing Cheng ◽  
Juncheng Wang ◽  
Ling Ma ◽  
Zhixiong Shen ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Biomedical Imaging ◽  
Frequency Dispersion ◽  
Light Sheet ◽  
Photonic Devices ◽  
Self Healing ◽  
Beam Focusing ◽  
Light Sheet Microscopy ◽  
Airy Beam ◽  
Potential Applications ◽  
Airy Beams

AbstractAiry beams exhibit intriguing properties such as nonspreading, self-bending, and self-healing and have attracted considerable recent interest because of their many potential applications in photonics, such as to beam focusing, light-sheet microscopy, and biomedical imaging. However, previous approaches to generate Airy beams using photonic structures have suffered from severe chromatic problems arising from strong frequency dispersion of the scatterers. Here, we design and fabricate a metasurface composed of silicon posts for the frequency range 0.4–0.8 THz in transmission mode, and we experimentally demonstrate achromatic Airy beams exhibiting autofocusing properties. We further show numerically that a generated achromatic Airy-beam-based metalens exhibits self-healing properties that are immune to scattering by particles and that it also possesses a larger depth of focus than a traditional metalens. Our results pave the way to the realization of flat photonic devices for applications to noninvasive biomedical imaging and light-sheet microscopy, and we provide a numerical demonstration of a device protocol.

The Use of Sonography in Pediatrics: The Bioethical Concerns in Clinical and Research Practice

2021 ◽  
pp. 875647932110350
Author(s):  
Nicole Weikle
Keyword(s):  
Clinical Setting ◽  
Imaging Modality ◽  
Pediatric Population ◽  
Well Being ◽  
Ethical Principles ◽  
Pediatric Care ◽  
Research Practice ◽  
Ethical Guidelines ◽  
Non Invasive ◽  
Clinical Pediatric

Sonography has been widely used in both a clinical and non-clinical setting. This imaging modality is a common tool of choice for both physicians and researchers. Although sonography is a non-ionizing and non-invasive tool for imaging, special considerations need to be made when working with the pediatric population. Ethical guidelines for clinical pediatric care and research need to consider the varying ethical guidelines and bioethical concerns in children. As sonographers, researchers, educators and clinicians, pediatric care and research must balance the protection of children and the need for imaging to improve pediatric well-being. The discussion of this paper will delve into The Principles Approach developed by Beauchamp and Childress. Each principle will be explored and how those ethical principles could be considered in pediatric care.

Sign in / Sign up

Export Citation Format

Share Document