scholarly journals Neuroinflammation and Precision Medicine in Pediatric Neurocritical Care: Multi-Modal Monitoring of Immunometabolic Dysfunction

2020 ◽  
Vol 21 (23) ◽  
pp. 9155
Author(s):  
Kristine E. Woodward ◽  
Pauline de Jesus ◽  
Michael J. Esser

The understanding of molecular biology in neurocritical care (NCC) is expanding rapidly and recognizing the important contribution of neuroinflammation, specifically changes in immunometabolism, towards pathological disease processes encountered across all illnesses in the NCC. Additionally, the importance of individualized inflammatory responses has been emphasized, acknowledging that not all individuals have the same mechanisms contributing towards their presentation. By understanding cellular processes that drive disease, we can make better personalized therapy decisions to improve patient outcomes. While the understanding of these cellular processes is evolving, the ability to measure such cellular responses at bedside to make acute care decisions is lacking. In this overview, we review cellular mechanisms involved in pathological neuroinflammation with a focus on immunometabolic dysfunction and review non-invasive bedside tools that have the potential to measure indirect and direct markers of shifts in cellular metabolism related to neuroinflammation. These tools include near-infrared spectroscopy, transcranial doppler, elastography, electroencephalography, magnetic resonance imaging and spectroscopy, and cytokine analysis. Additionally, we review the importance of genetic testing in providing information about unique metabolic profiles to guide individualized interpretation of bedside data. Together in tandem, these modalities have the potential to provide real time information and guide more informed treatment decisions.

Physiology ◽  
2009 ◽  
Vol 24 (1) ◽  
pp. 58-71 ◽  
Author(s):  
George Osol ◽  
Maurizio Mandala

Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.


2020 ◽  
Author(s):  
Jiongru Pan ◽  
Han Deng ◽  
Shiqi Hu ◽  
Chengwan Xia ◽  
Yongfeng Chen ◽  
...  

Abstract Background Local recurrence is the main cause of death among patients with oral squamous cell carcinoma (OSCC). This study assessed near-infrared fluorescence (NIF) imaging and spectroscopy to monitor surgical margins intraoperative for OSCC. Methods Cytological and animal experiments were first performed to confirm the feasibility of monitoring surgical margins with NIF imaging and spectroscopy. Then, 20 patients with OSCC were included in the clinical trials. At 6–8 hours after 0.75 mg/kg indocyanine green (ICG) injection, all patients underwent surgery with NIF imaging. During the surgery, both NIF images and quantified fluorescence intensity were acquired to monitor the surgical margins. Results In cytological and animal experiments, the results showed it is feasible to monitor surgical margins with NIF imaging and spectroscopy. Fluorescence was detected in primary tumors in all patients. The fluorescence intensities of the tumor, peritumoral, and normal tissues were 398.863±151.47, 278.52±84.89, and 274.5±100.93 arbitrary units (AUs), respectively (P<0.05). The SBR of tumor to peritumoral tissue and normal tissues was computed to be 1.45±0.36 and 1.56±0.41 respectively. After primary tumor excision, the wounds showed abnormal fluorescence in four patients (4/20), and residual cancer cells were confirmed by pathological examination in two patients (2/20). Conclusion These findings confirmed the complementary value of NIF imaging during radical tumor resection of OSCC.


2014 ◽  
Vol 1 (1) ◽  
pp. 222-226
Author(s):  
Kumiko Morihana ◽  
Masahiro Tsujimoto ◽  
Ken Ebisawa

We present the results of X-ray and Near-Infrared observations of the Galactic Ridge X-ray Emission (GRXE). We extracted 2,002 X-ray point sources in the <em>Chandra</em> Bulge Field (l =0°.113, b = 1°.424) down to ~10<sup>-14.8</sup> ergscm<sup>-2</sup>s<sup>-1</sup> in 2-8 keV band with the longest observation (900 ks) of the GRXE. Based on X-ray brightness and hardness, we classied the X-ray point sources into three groups: A (hard), B (soft and broad spectrum), and C (soft and peaked spectrum). In order to know populations of the X-ray point sources, we carried out NIR imaging and spectroscopy observation. We identied 11% of X-ray point sources with NIR and extracted NIR spectra for some of them. Based on X-ray and NIR properties, we concluded that non-thermal sources in the group A are mostly active galactic nuclei and the thermal sources are mostly white dwarf binaries such as cataclysmic variables (CVs) and Pre-CVs. We concluded that the group B and C sources are X-ray active stars in flare and quiescence, respectively.


Author(s):  
Kristin Guilliams ◽  
Andranik Madikians ◽  
Jose Pineda ◽  
Christopher C. Giza

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Harvey F Chin ◽  
Abigail Haka ◽  
Frederick R Maxfield

Macrophages encounter deposits of aggregated low-density lipoproteins (agLDL) in the subendothelial space of blood vessels during the first stages of atherosclerotic plaque formation. Notably, current models for the mechanism of macrophage internalization of cholesterol in early atherosclerotic plaques are incomplete due to the lack of attention paid to the unique cellular mechanisms that are required for macrophages to degrade aggregates of LDL in particular, which can comprise >90% of the LDL in atherosclerotic plaques. In fact, internalization of cholesterol from cholesteryl esters in agLDL involves the development of intriguing cellular processes in which extracellular acidic compartments, lysosomal synapses (LSs), are formed whereby agLDL is partially degraded prior to internalization. This process requires extensive cytoskeletal rearrangements and secretion of lysosomal enzymes responsible for hydrolysis of cholesteryl esters from the agLDL. Subsequent delivery of free cholesterol from agLDL to the macrophage plasma membrane is central for development of the LS. Nonetheless, the molecular mechanism underlying initiation and propagation of the LS are currently largely unknown. This research proposal aims to elucidate the molecular mechanisms of LS formation and the role that cholesterol plays in eliciting these morphological responses to agLDL. Fluorescence microscopy assays were used to identify activation of TLR4 and downstream signaling involving PI3K and Akt as important events leading to LS formation. Furthermore, morphological responses of macrophages to cholesterol overloading require overlapping signaling pathways, indicating the role of interplay of cholesterol and TLR4 signaling in development of this novel macrophage interaction with aggregated LDL found in plaques. Identification of specific molecular pathways involved in this process will not only contribute to the basic understanding of one of the primary cellular processes contributing to atherosclerosis, one of the primary causes of heart disease, but also provide tangible molecular targets for the ultimate development of therapies.


2019 ◽  
Vol 20 (6) ◽  
pp. 540-550 ◽  
Author(s):  
Ericka L. Fink ◽  
Sue R. Beers ◽  
Amy J. Houtrow ◽  
Rudolph Richichi ◽  
Cheryl Burns ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Carlos Velásquez ◽  
Sheila Mansouri ◽  
Carla Mora ◽  
Farshad Nassiri ◽  
Suganth Suppiah ◽  
...  

The invasive capacity of GBM is one of the key tumoral features associated with treatment resistance, recurrence, and poor overall survival. The molecular machinery underlying GBM invasiveness comprises an intricate network of signaling pathways and interactions with the extracellular matrix and host cells. Among them, PI3k/Akt, Wnt, Hedgehog, and NFkB play a crucial role in the cellular processes related to invasion. A better understanding of these pathways could potentially help in developing new therapeutic approaches with better outcomes. Nevertheless, despite significant advances made over the last decade on these molecular and cellular mechanisms, they have not been translated into the clinical practice. Moreover, targeting the infiltrative tumor and its significance regarding outcome is still a major clinical challenge. For instance, the pre- and intraoperative methods used to identify the infiltrative tumor are limited when trying to accurately define the tumor boundaries and the burden of tumor cells in the infiltrated parenchyma. Besides, the impact of treating the infiltrative tumor remains unclear. Here we aim to highlight the molecular and clinical hallmarks of invasion in GBM.


2018 ◽  
Vol 46 (1) ◽  
pp. 394-394 ◽  
Author(s):  
Ericka Fink ◽  
Sue Beers ◽  
Amy Houtrow ◽  
Rudolph Richichi ◽  
Cheryl Burns ◽  
...  

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