scholarly journals Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry

2019 ◽  
Vol 5 (3) ◽  
pp. eaaw0873 ◽  
Author(s):  
Hao Zhang ◽  
Philipp Gutruf ◽  
Kathleen Meacham ◽  
Michael C. Montana ◽  
Xingyue Zhao ◽  
...  
Keyword(s):  
Animal Models ◽  
Tissue Oxygenation ◽  
Human Subjects ◽  
Brain Regions ◽  
Disease States ◽  
Data Output ◽  
Subdermal Implants ◽  
Underlying Mechanisms ◽  
Tissue Oximetry

Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.

scholarly journals Effects of ornithine α-ketoglutarate on insulin secretion in rat pancreatic islets: implication of nitric oxide synthase and glutamine synthetase pathways

2003 ◽  
Vol 89 (2) ◽  
pp. 249-257 ◽  
Author(s):  
Christina Schneid ◽  
Sylviane Darquy ◽  
Luc Cynober ◽  
Gérard Reach ◽  
Jean-Pascal De Bandt
Keyword(s):  
Insulin Secretion ◽  
Islets Of Langerhans ◽  
Human Subjects ◽  
Mechanisms Of Action ◽  
Methionine Sulfoximine ◽  
Underlying Mechanisms ◽  
Rat Islets Of Langerhans ◽  
Oxide Synthase ◽  
Kinetics Of

Ornithine α-ketoglutarate (OKG) administration in human subjects elicits insulin secretion. We investigated whether this action was related to an effect of OKG on islets of Langerhans, and addressed the underlying mechanisms of action. For this purpose the influence of OKG on insulin secretion was measured in isolated rat islets of Langerhans under two different conditions. In incubated islets, OKG (0·25 to 2·5 mmol/l) significantly and dose-relatedly increased insulin secretion (1·7- to 4·2-fold; P<0·05 v. basal). To study the kinetics of OKG-stimulated insulin secretion, perifusion experiments were performed, which showed that OKG affected insulin secretion in both initial and later phases. Experiments using α-ketoglutarate (α-KG) (1 mmol/l) or ornithine (Orn) (2 mmol/l) alone, in concentrations equal to that of OKG, showed that the OKG-induced insulin secretion could not be obtained by either component alone, suggesting that an α-KG–Orn interaction is mandatory for the insulin-secreting effect to occur. Since data obtained in vivo suggest that effects of OKG may depend on the synthesis of NO, glutamine and/or polyamines, three metabolic pathways potentially involved in insulin secretion, we then evaluated their contribution by means of their respective inhibitors: α-NG-nitroarginine methyl ester (l-NAME), methionine sulfoximine (MSO) and difluoromethylornithine (DFMO). Both l-NAME and MSO were able significantly to reduce OKG-induced insulin secretion (30 and 40 % respectively; P<0·05), while DFMO was ineffective. Thus OKG is an effective stimulator of insulin secretion, requiring the joint presence of both Orn and α-KG, and acting mainly via the synthesis of NO and glutamine. A better understanding of OKG insulino-secretory properties and its mechanisms of action are a prerequisite for its use in insulin-compromised situations.

scholarly journals P62 accumulates through neuroanatomical circuits in response to tauopathy propagation

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
François-Xavier Blaudin de Thé ◽  
Benjamin Lassus ◽  
Ari W. Schaler ◽  
Stephanie L. Fowler ◽  
Chris N. Goulbourne ◽  
...  
Keyword(s):  
Disease Progression ◽  
Brain Regions ◽  
In Vitro Models ◽  
Tau Pathology ◽  
Neuron Models ◽  
Protein Clearance ◽  
Underlying Mechanisms ◽  
Tau Aggregation

AbstractIn Alzheimer’s disease and related tauopathies, trans-synaptic transfer and accumulation of pathological tau from donor to recipient neurons is thought to contribute to disease progression, but the underlying mechanisms are poorly understood. Using complementary in vivo and in vitro models, we examined the relationship between these two processes and neuronal clearance. Accumulation of p62 (a marker of defective protein clearance) correlated with pathological tau accumulation in two mouse models of tauopathy spread; Entorhinal Cortex-tau (EC-Tau) mice where tau pathology progresses in time from EC to other brain regions, and PS19 mice injected with tau seeds. In both models and in several brain regions, p62 colocalized with human tau in a pathological conformation (MC1 antibody). In EC-Tau mice, p62 accumulated before overt tau pathology had developed and was associated with the presence of aggregation-competent tau seeds identified using a FRET-based assay. Furthermore, p62 accumulated in the cytoplasm of neurons in the dentate gyrus of EC-Tau mice prior to the appearance of MC1 positive tauopathy. However, MC1 positive tau was shown to be present at the synapse and to colocalize with p62 as shown by immuno electron microscopy. In vitro, p62 colocalized with tau inclusions in two primary cortical neuron models of tau pathology. In a three-chamber microfluidic device containing neurons overexpressing fluorescent tau, seeding of tau in the donor chamber led to tau pathology spread and p62 accumulation in both the donor and the recipient chamber. Overall, these data are in accordance with the hypothesis that the accumulation and trans-synaptic spread of pathological tau disrupts clearance mechanisms, preceding the appearance of obvious tau aggregation. A vicious cycle of tau accumulation and clearance deficit would be expected to feed-forward and exacerbate disease progression across neuronal circuits in human tauopathies.

Optical Detection of Tumors In Vivo by Visible Light Tissue Oximetry

2005 ◽  
Vol 4 (3) ◽  
pp. 227-234 ◽  
Author(s):  
Peter G. Maxim ◽  
Jeffrey J. L. Carson ◽  
David A. Benaron ◽  
Billy W. Loo ◽  
Lei Xing ◽  
...  
Keyword(s):  
Visible Light ◽  
Real Time ◽  
Normal Tissue ◽  
Tissue Oxygenation ◽  
Human Subjects ◽  
Standard Procedure ◽  
Human Tumor ◽  
Tumor Oxygenation ◽  
Local Ischemia ◽  
Tissue Oximetry

Endoscopy is a standard procedure for identifying tumors in patients suspected of having gastrointestinal (G.I.) cancer. The early detection of G.I. neoplasms during endoscopy is currently made by a subjective visual inspection that relies to a high degree on the experience of the examiner. This process can be difficult and unreliable, as tumor lesions may be visually indistinguishable from benign inflammatory conditions and the surrounding mucosa. In this study, we evaluated the ability of local ischemia detection using visible light spectroscopy (VLS) to differentiate neoplastic from normal tissue based on capillary tissue oxygenation during endoscopy. Real-time data were collected (i) from human subjects (N=34) monitored at various sites during endoscopy (enteric mucosa, malignant, and abnormal tissue such as polyps) and (ii) murine animal subjects with human tumor xenografts. Tissue oximetry in human subjects during endoscopy revealed a tissue oxygenation (StO2%, mean ± SD) of 46 ± 22% in tumors, which was significantly lower than for normal mucosal oxygenation (72 ± 4%; P ≤ 0.0001). No difference in tissue oxygenation was observed between normal and non-tumor abnormal tissues ( P = N.S.). Similarly, VLS tissue oximetry for murine tumors revealed a mean local tumor oxygenation of 45% in LNCaP, 50% in M21, and 24% in SCCVII tumors, all significantly lower than normal muscle tissue (74%, P < 0.001). These results were further substantiated by positive controls, where a rapid real-time drop in tumor oxygenation was measured during local ischemia induced by clamping or epinephrine. We conclude that VLS tissue oximetry can distinguish neoplastic tissue from normal tissue with a high specificity (though a low sensitivity), potentially aiding the endoscopic detection of gastrointestinal tumors.

scholarly journals Carbon Nanoelectrodes for the Electrochemical Detection of Neurotransmitters

2018 ◽  
Vol 2018 ◽  
pp. 1-19 ◽  
Author(s):  
Alexander G. Zestos
Keyword(s):  
Electrode Materials ◽  
Brain Regions ◽  
Fused Silica ◽  
Carbon Fiber Microelectrode ◽  
Disease States ◽  
Surface Areas ◽  
Fused Silica Capillaries ◽  
Living Organisms ◽  
Carbon Based

Carbon-based electrodes have been developed for the detection of neurotransmitters over the past 30 years using voltammetry and amperometry. The traditional electrode for neurotransmitter detection is the carbon fiber microelectrode (CFME). The carbon-based electrode is suitable for in vivo neurotransmitter detection due to the fact that it is biocompatible and relatively small in surface area. The advent of nanoscale electrodes is in high demand due to smaller surface areas required to target specific brain regions that are also minimally invasive and cause relatively low tissue damage when implanted into living organisms. Carbon nanotubes (CNTs), carbon nanofibers, carbon nanospikes, and carbon nanopetals among others have all been utilized for this purpose. Novel electrode materials have also required novel insulations such as glass, epoxy, and polyimide coated fused silica capillaries for their construction and usage. Recent research developments have yielded a wide array of carbon nanoelectrodes with superior properties and performances in comparison to traditional electrode materials. These electrodes have thoroughly enhanced neurotransmitter detection allowing for the sensing of biological compounds at lower limits of detection, fast temporal resolution, and without surface fouling. This will allow for greater understanding of several neurological disease states based on the detection of neurotransmitters.

The cannabinoid CB1 receptor biphasically modulates motor activity and regulates dopamine and glutamate release region dependently

2012 ◽  
Vol 16 (2) ◽  
pp. 393-403 ◽  
Author(s):  
Alexia Polissidis ◽  
Andreas Galanopoulos ◽  
George Naxakis ◽  
Demetris Papahatjis ◽  
Zeta Papadopoulou-Daifoti ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Glutamate Release ◽  
Brain Regions ◽  
Cb1 Receptor ◽  
Glutamatergic Neurotransmission ◽  
Extracellular Dopamine ◽  
Cb1 Antagonist ◽  
Subcortical Regions ◽  
Underlying Mechanisms

Abstract Cannabinoid administration modulates both dopaminergic and glutamatergic neurotransmission. The present study examines the effects of high and low dose WIN55,212-2, a CB1 receptor agonist, on extracellular dopamine and glutamate release in vivo via brain microdialysis in the nucleus accumbens (NAc), striatum and prefrontal cortex (PFC) in parallel to its effects on locomotor activity. WIN55,212-2 increased extracellular dopamine in the NAc (1 mg/kg i.p.), striatum (0.1 and 1 mg/kg i.p.) and PFC (1 mg/kg i.p.). Glutamate release was also elevated by WIN55,212-2 in the PFC (1 mg/kg i.p.) whereas in the NAc (0.1 and 1 mg/kg i.p.) and striatum, it was reduced (1 mg/kg i.p.). WIN55,212-2 administration produced hyperlocomotion at the lower dose (0.1 mg/kg i.p.) and hypolocomotion at the higher dose (1 mg/kg i.p.). Co-administration with the CB1 antagonist, SR-141716A (0.03 mg/kg i.p.), prevented the above effects. According to the present results, WIN55,212-2 affected locomotor activity biphasically while exerting converging effects on dopamine activity but diverging effects on glutamate release between cortical and subcortical regions, especially at the higher dose. These findings emphasize the involvement of the CB1 receptor in the simultaneous modulation of dopaminergic and glutamatergic neurotransmission in brain regions involved in reward and locomotion and suggest possible underlying mechanisms of acute cannabinoid exposure and its psychoactive and behavioural manifestations.

scholarly journals Omentin-1 Modulates Macrophage Function via Integrin Receptors αvβ3 and αvβ5 and Reverses Plaque Vulnerability in Animal Models of Atherosclerosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Xuze Lin ◽  
Yan Sun ◽  
Shiwei Yang ◽  
Mengyue Yu ◽  
Liu Pan ◽  
...  
Keyword(s):  
Animal Models ◽  
Inflammatory Cytokines ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Integrin Subunit ◽  
Integrin Receptors ◽  
Macrophage Function ◽  
Underlying Mechanisms ◽  
Pro Inflammatory Cytokines

Backgrounds: Omentin-1 is a novel cytokine that is primarily released by the epicardial adipose tissue. Molecular structure analysis revealed that it contained a fibrinogen-like domain. Clinical studies have demonstrated that the expression of omentin-1 is tightly associated with the development of cardiovascular diseases, but the receptor by which omentin-1 modulates macrophage function has not been identified yet.Objective: This study sought to investigate the effect of omentin-1 on already-established atherosclerosis (AS) lesions in both ApoE−/− and Ldlr−/− mice and further, study its underlying mechanisms.Methods and Results: We investigated the effect of omentin-1 on the plaque phenotype by implanting a minipump in ApoE−/− and Ldlr−/− mice. In vivo studies showed that the infusion of omentin-1 increased the collagen content and mitigated the formation of the necrotic core in both animal models. Immunohistochemistry and immunofluorescence analysis revealed that omentin-1 suppressed inflammatory cytokines expression, macrophage infiltration, and apoptosis within the plaque. An immunoprecipitation experiment and confocal microscopy analysis confirmed the binding of omentin-1 to the integrin receptors αvβ3 and αvβ5. The cell studies demonstrated that omentin-1 suppressed the apoptosis and inflammatory cytokines expression induced by the oxidized low-density lipoprotein in the macrophage. In addition, omentin-1 promoted the phosphorylation of the integrin-relevant signaling pathway as well as the Akt and AMPK in the macrophage. The addition of the inhibitor of the integrin receptor or interfering with the expression of the integrin subunit αv (ITGAV) both significantly abrogated the bioeffects induced by omentin-1. A flow cytometry analysis indicated that the antibodies against αvβ3 and αvβ5 had a competitive effect on the omentin-1 binding to the cell membrane.Conclusions: The administration of adipokine omentin-1 can inhibit the necrotic cores formation and pro-inflammatory cytokines expression within the AS lesion. The mechanisms may include the suppression of apoptosis and pro-inflammatory cytokines expression in the macrophage by binding to the integrin receptors αvβ3 and αvβ5.

scholarly journals In Vivo Structural and Functional Abnormalities of the Striatums Is Related to Decreased Astrocytic BDNF in Itpr2-/- Mice Exhibiting Depressive-Like Behavior

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Shanmei Zeng ◽  
Kai Liu ◽  
Jingyu Zhang ◽  
Chunhui Chen ◽  
Yihua Xu ◽  
...  
Keyword(s):  
Gray Matter ◽  
Gray Matter Volume ◽  
Brain Regions ◽  
Specific Pattern ◽  
Brain Abnormalities ◽  
Matter Volume ◽  
Secondary Somatosensory Cortex ◽  
Underlying Mechanisms ◽  
The Right

Background. Previous researches indicate that Itpr2-/- mice (inositol 1,4,5-trisphosphate receptor type 2 knockout mice) show depressive-like symptoms; however, little is known regarding the in vivo neurobiological effect of Itpr2 as well as the specific pattern of brain abnormalities in Itpr2-/- mice. Methods/Materials. First, behavioral tests, structural magnetic resonance imaging (MRI), and resting-state functional MRI were performed on Itpr2-/- mice and matched healthy controls. Voxel-based morphometry and seed-based voxel-wise functional connectivity (FC) were, respectively, calculated to assess the gray matter volume and the functional activities of the brain in vivo. Second, the sample of relevant changed brain regions was extracted to detect the expression of BDNF. Finally, to further validate the relationship between Itpr2 deficiency and the observed brain abnormalities, we performed Western blotting to detect the expression of pro-BDNF and mBDNF in Itpr2-/- C8-D1A (a type of astrocyte). Results. Compared with controls, Itpr2-/- mice showed depressive-like behaviors as well as significantly lower gray matter volume in striatums mainly, periaqueductal GM, and the right frontoparietal cortices as well as lower striatal-hippocampal and striatal-right parietal cortex (mainly for the primary and secondary somatosensory cortex) FC. Moreover, decreased expression of mBDNF was found in both sample tissues of the striatum in Itpr2-/- mice and Itpr2-/- C8-D1A. Conclusion. By combining biochemistry and MR analyses, this study provides evidences to support that the Itpr2-related neuropathological effect is possibly mediated by the striatal abnormality associated with dysfunctional astrocytes in Itpr2-/- mice in vivo, thus may help us better understand underlying mechanisms of Itpr2 deficiency as well as its relation to depressive-like behavior.

scholarly journals Renal depletion of myo-inositol is associated with its increased degradation in animal models of metabolic disease

2015 ◽  
Vol 309 (9) ◽  
pp. F755-F763 ◽  
Author(s):  
H.-H. Chang ◽  
H.-N. Chao ◽  
C. S. Walker ◽  
S.-Y. Choong ◽  
A. Phillips ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disease ◽  
Animal Models ◽  
De Novo ◽  
Insulin Resistant ◽  
Disease States ◽  
Expression Of Genes ◽  
Pathological Mechanism ◽  
Distinct Disease ◽  
Underlying Mechanisms

Renal depletion of myo-inositol (MI) is associated with the pathogenesis of diabetic nephropathy in animal models, but the underlying mechanisms involved are unclear. We hypothesized that MI depletion was due to changes in inositol metabolism and therefore examined the expression of genes regulating de novo biosynthesis, reabsorption, and catabolism of MI. We also extended the analyses from diabetes mellitus to animal models of dietary-induced obesity and hypertension. We found that renal MI depletion was pervasive across these three distinct disease states in the relative order: hypertension (−51%) > diabetes mellitus (−35%) > dietary-induced obesity (−19%). In 4-wk diabetic kidneys and in kidneys derived from insulin-resistant and hypertensive rats, MI depletion was correlated with activity of the MI-degrading enzyme myo-inositol oxygenase (MIOX). By contrast, there was decreased MIOX expression in 8-wk diabetic kidneys. Immunohistochemistry localized the MI-degrading pathway comprising MIOX and the glucuronate-xylulose (GX) pathway to the proximal tubules within the renal cortex. These findings indicate that MI depletion could reflect increased catabolism through MIOX and the GX pathway and implicate a common pathological mechanism contributing to renal oxidative stress in metabolic disease.

scholarly journals Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

2019 ◽  
Author(s):  
Cleiton Lopes-Aguiar ◽  
Rafael N. Ruggiero ◽  
Matheus T. Rossignoli ◽  
Ingrid de Miranda Esteves ◽  
José Eduardo Peixoto Santos ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Plasticity ◽  
Animal Models ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
High Frequency Stimulation ◽  
Evoked Responses ◽  
Term Potentiation

ABSTRACTN-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and synaptic plasticity in key brain regions related with schizophrenia, particularly in the hippocampus and the prefrontal cortex. In contrast, long-term potentiation (LTP) induction is known to increase glutamatergic transmission. Thus, we hypothesized that LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma crossfrequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits.

scholarly journals Treatment of Lymphedema with Cell-Based Therapies: A Systematic Review

2020 ◽  
Vol 3 ◽  
Author(s):  
Connor Drake ◽  
Lily Suh ◽  
Colby Neumann ◽  
Imran Khan ◽  
Mithun Sinha ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Animal Models ◽  
English Language ◽  
Human Subjects ◽  
Immunosuppressive Agents ◽  
Parasitic Infection ◽  
Cell Transplant ◽  
Compression Garments ◽  
In Vivo Models

Introduction  Lymphedema is a chronic condition that affects over 250 million people worldwide. It results from impaired lymphatic drainage, causing fluid and fat accumulation and eventually fibrosis of the affected limb. Lymphedema can be inherited (primary) or iatrogenic to surgery or parasitic infection (secondary). Breast cancer-related lymphedema is the most common etiology in the U.S. Current treatments have limited success and the disease mechanisms are not well understood. The purpose of this article is to review translational research into lymphedema therapies and its potential clinical impact.     Methods  A Pubmed search for novel treatment methods was performed with terms “lymphedema,” “cell therapy,” and “gene therapy.” Inclusion criteria were use of in vivo models, English language, and publication dates during the years 2000-2020.    Results  Secondary lymphedema is currently treated with compression garments and surgery; other approaches are being pursued. These include gene therapy (13 articles), stem cell transplant (16 articles), and immunosuppression (4 articles), which have all demonstrated considerable success in animal models of lymphedema. Growth factors such as VEGF-C are administered through adenoviral vectors and resolve limb swelling by inducing lymphangiogenesis. Stem cells derived from bone marrow or adipose tissue repair lymphatic damage directly by acquiring lymphatic characteristics or indirectly through paracrine signaling to surrounding cells. Immunosuppressive agents reduce inflammation and block antilymphangiogenic factors. Although these mechanisms have been studied in animals, only six human small studies were found, providing limited evidence.     Conclusion  Despite success in animal models, treatment in human subjects has been sparse. This limited translational feasibility is because of inadequate animal models, safety concerns, and lack of understanding about lymphedema pathophysiology. Although progress in lymphedema research has been made, further inquiry into its mechanism is needed in order to develop more effective and targeted therapies. 

Sign in / Sign up

Export Citation Format

Share Document