scholarly journals A Skull-Removed Chronic Cranial Window for Ultrasound and Photoacoustic Imaging of the Rodent Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Xuanhao Wang ◽  
Yan Luo ◽  
Yuwen Chen ◽  
Chaoyi Chen ◽  
Lu Yin ◽  
...  

Ultrasound and photoacoustic imaging are emerging as powerful tools to study brain structures and functions. The skull introduces significant distortion and attenuation of the ultrasound signals deteriorating image quality. For biological studies employing rodents, craniotomy is often times performed to enhance image qualities. However, craniotomy is unsuitable for longitudinal studies, where a long-term cranial window is needed to prevent repeated surgeries. Here, we propose a mouse model to eliminate sound blockage by the top portion of the skull, while minimum physiological perturbation to the imaged object is incurred. With the new mouse model, no craniotomy is needed before each imaging experiment. The effectiveness of our method was confirmed by three imaging systems: photoacoustic computed tomography, ultrasound imaging, and photoacoustic mesoscopy. Functional photoacoustic imaging of the mouse brain hemodynamics was also conducted. We expect new applications to be enabled by the new mouse model for photoacoustic and ultrasound imaging.

Author(s):  
Yongchao Wang ◽  
Lei Xi

AbstractPhotoacoustic (PA) microscopy is being increasingly used to visualize the microcirculation of the brain cortex at the micron level in living rodents. By combining it with long-term cranial window techniques, vasculature can be monitored over a period of days extending to months through a field of view. To fulfill the requirements of long-term in vivo PA imaging, the cranial window must involve a simple and rapid surgical procedure, biological compatibility, and sufficient optical-acoustic transparency, which are major challenges. Recently, several cranial window techniques have been reported for longitudinal PA imaging. Here, the development of chronic cranial windows for PA imaging is reviewed and its technical details are discussed, including window installation, imaging quality, and longitudinal stability.


Author(s):  
Yongchao Wang ◽  
Guangru Liang ◽  
Fei Liu ◽  
Qian Chen ◽  
Lei Xi

2020 ◽  
Author(s):  
Masayasu Taki ◽  
Keiji Kajiwara ◽  
Eriko Yamaguchi ◽  
Yoshikatsu Sato ◽  
Shigehiro Yamaguchi

Lipid droplets (LDs) are essential organelle in most eukaryotes, and tracking intracellular LDs dynamics using synthetic small molecules is crucial for biological studies. However, only a limited number of fluorescent markers that satisfy all requirements, such as the selective staining of LDs, high photostability, and sufficient biocompatibility, have been developed. Herein, we report a series of donor-p-acceptor dyes based on the thiophene-containing fused polycyclic scaffold [1]benzothieno[3,2-<i>b</i>][1]benzothiophene (BTBT), in which either or both thiophene rings are oxidized into thiophene-<i>S</i>,<i>S</i>-dioxide to form an electron-accepting building block. Among these dyes, LAQ1 satisfied all the aforementioned requirements, and allowed us capturing ultra-small LDs on the endoplasmic reticulum (ER) membrane by stimulation emission depletion (STED) microscopy with a super-resolution below the diffraction limit of light. Moreover, the extremely high photostability of LAQ1 enabled recording the lipolysis of LDs and the concomitant lipogenesis as well as long-term trajectory analysis of micro LDs at the single particle level in living cells.


2020 ◽  
Vol 8 (2) ◽  
pp. e001513
Author(s):  
Nahee Park ◽  
Kamal Pandey ◽  
Sei Kyung Chang ◽  
Ah-Young Kwon ◽  
Young Bin Cho ◽  
...  

BackgroundWell-characterized preclinical models are essential for immune-oncology research. We investigated the feasibility of our humanized mouse model for evaluating the long-term efficacy of immunotherapy and biomarkers.MethodsHumanized mice were generated by injecting human fetal cord blood-derived CD34+ hematopoietic stem cells to NOD-scid IL2rγnull (NSG) mice myeloablated with irradiation or busulfan. The humanization success was defined as a 25% or higher ratio of human CD45+ cells to mice peripheral blood mononuclear cells.ResultsBusulfan was ultimately selected as the appropriate myeloablative method because it provided a higher success rate of humanization (approximately 80%) and longer survival time (45 weeks). We proved the development of functional T cells by demonstrating the anticancer effect of the programmed cell death-1 (PD-1) inhibitor in our humanized mice but not in non-humanized NSG mice. After confirming the long-lasting humanization state (45 weeks), we further investigated the response durability of the PD-1 inhibitor and biomarkers in our humanized mice. Early increase in serum tumor necrosis factor α levels, late increase in serum interleukin 6 levels and increase in tumor-infiltrating CD8+ T lymphocytes correlated more with a durable response over 60 days than with a non-durable response.ConclusionsOur CD34+ humanized mouse model is the first in vivo platform for testing the long-term efficacy of anticancer immunotherapies and biomarkers, given that none of the preclinical models has ever been evaluated for such a long duration.


2021 ◽  
pp. 107385842199668
Author(s):  
Simone G. Shamay-Tsoory

Social interactions are powerful determinants of learning. Yet the field of neuroplasticity is deeply rooted in probing changes occurring in synapses, brain structures, and networks within an individual brain. Here I synthesize disparate findings on network neuroplasticity and mechanisms of social interactions to propose a new approach for understanding interaction-based learning that focuses on the dynamics of interbrain coupling. I argue that the facilitation effect of social interactions on learning may be explained by interbrain plasticity, defined here as the short- and long-term experience-dependent changes in interbrain coupling. The interbrain plasticity approach may radically change our understanding of how we learn in social interactions.


2021 ◽  
pp. 1098612X2110236
Author(s):  
Elisa P McEntee ◽  
Allyson C Berent ◽  
Chick Weisse ◽  
Alexandre Le Roux ◽  
Kenneth Lamb

Objectives The aim of this study was to determine whether preoperative ultrasound imaging characteristic(s) in cats suffering from unilateral benign ureteral obstructions are predictive of outcome after successful renal decompression with a subcutaneous ureteral bypass (SUB) device. Methods This was a retrospective study of 37 cats with unilateral, benign ureteral obstruction. Preoperative imaging characteristics (including renal pelvis diameter, parenchymal thickness [transverse plane], renal length and pelvic size:overall renal size) and biochemical data were evaluated for all cats diagnosed with a unilateral ureteral obstruction treated with a SUB device. Any patient with bilateral obstructions or documented bacteriuria/infection in the data collection period was excluded. All patients were followed between 3 and 6 months postoperatively to obtain postoperative biochemical data. Long-term outcome was defined as serum creatinine concentration at 3–6 months postoperatively. Results No preoperative imaging characteristics or biochemical findings were found to be significantly associated with long-term serum creatinine concentrations. The length of the kidney was found to be associated with change in blood urea nitrogen and creatinine with decompression but not with long-term renal values. Conclusions and relevance In this study, long-term renal function based on preoperative ultrasound imaging findings could not be predicted in cats with unilateral ureteral obstruction, regardless of the severity of the biochemical parameters, renal pelvic dilation (large or small pelvis), kidney size or thickness of renal parenchyma assessed.


2021 ◽  
pp. 174702182110105
Author(s):  
Spencer Talbot ◽  
Todor Gerdjikov ◽  
Carlo De Lillo

Assessing variations in cognitive function between humans and animals is vital for understanding the idiosyncrasies of human cognition and for refining animal models of human brain function and disease. We determined memory functions deployed by mice and humans to support foraging with a search task acting as a test battery. Mice searched for food from the top of poles within an open-arena. Poles were divided into groups based on visual cues and baited according to different schedules. White and black poles were baited in alternate trials. Striped poles were never baited. The requirement of the task was to find all baits in each trial. Mice’s foraging efficiency, defined as the number of poles visited before all baits were retrieved, improved with practice. Mice learnt to avoid visiting un-baited poles across trials (Long-term memory) and revisits to poles within each trial (Working memory). Humans tested with a virtual-reality version of the task outperformed mice in foraging efficiency, working memory and exploitation of the temporal pattern of rewards across trials. Moreover, humans, but not mice, reduced the number of possible movement sequences used to search the set of poles. For these measures interspecies differences were maintained throughout three weeks of testing. By contrast, long-term-memory for never-rewarded poles was similar in mice and humans after the first week of testing. These results indicate that human cognitive functions relying upon archaic brain structures may be adequately modelled in mice. Conversely, modelling in mice fluid skills likely to have developed specifically in primates, requires caution.


2020 ◽  
pp. 1-16
Author(s):  
Margaret Ryan ◽  
Valerie T.Y. Tan ◽  
Nasya Thompson ◽  
Diane Guévremont ◽  
Bruce G. Mockett ◽  
...  

Background: Secreted amyloid precursor protein-alpha (sAPPα) can enhance memory and is neurotrophic and neuroprotective across a range of disease-associated insults, including amyloid-β toxicity. In a significant step toward validating sAPPα as a therapeutic for Alzheimer’s disease (AD), we demonstrated that long-term overexpression of human sAPPα (for 8 months) in a mouse model of amyloidosis (APP/PS1) could prevent the behavioral and electrophysiological deficits that develop in these mice. Objective: To explore the underlying molecular mechanisms responsible for the significant physiological and behavioral improvements observed in sAPPα-treated APP/PS1 mice. Methods: We assessed the long-term effects on the hippocampal transcriptome following continuous lentiviral delivery of sAPPα or empty-vector to male APP/PS1 mice and wild-type controls using Affymetrix Mouse Transcriptome Assays. Data analysis was carried out within the Affymetrix Transcriptome Analysis Console and an integrated analysis of the resulting transcriptomic data was performed with Ingenuity Pathway analysis (IPA). Results: Mouse transcriptome assays revealed expected AD-associated gene expression changes in empty-vector APP/PS1 mice, providing validation of the assays used for the analysis. By contrast, there were specific sAPPα-associated gene expression profiles which included increases in key neuroprotective genes such as Decorin, betaine-GABA transporter, and protocadherin beta-5, subsequently validated by qRT-PCR. An integrated biological pathways analysis highlighted regulation of GABA receptor signaling, cell survival, and inflammatory responses. Furthermore, upstream gene regulatory analysis implicated sAPPα activation of Interleukin-4, which can counteract inflammatory changes in AD. Conclusion: This study identified key molecular processes that likely underpin the long-term neuroprotective and therapeutic effects of increasing sAPPα levels in vivo


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