scholarly journals Ménage à Trois: The Role of Neurotransmitters in the Energy Metabolism of Astrocytes, Glutamatergic, and GABAergic Neurons

2012 ◽  
Vol 32 (8) ◽  
pp. 1472-1483 ◽  
Author(s):  
Daniela Calvetti ◽  
Erkki Somersalo

This work is a computational study based on a new detailed metabolic network model comprising well-mixed compartments representing separate cytosol and mitochondria of astrocytes, glutamatergic and gamma aminobutyric acid (GABA)ergic neurons, communicating through an extracellular space compartment and fed by arterial blood flow. Our steady-state analysis assumes statistical mass balance of both carbons and amino groups. The study is based on Bayesian flux balance analysis, which uses Markov chain Monte Carlo sampling techniques and provides a quantitative description of steady states when the two exchangers aspartate-glutamate carrier (AGC1) and oxoglutarate carrier (OGC) in the malate-aspartate shuttle in astrocyte are not in equilibrium, as recent studies suggest. It also highlights the importance of anaplerotic reactions, pyruvate carboxylase in astrocyte and malic enzyme in neurons, for neurotransmitter synthesis and recycling. The model is unbiased with respect to the glucose partitioning between cell types, and shows that determining the partitioning cannot be done by stoichiometric constraints alone. Furthermore, the intercellular lactate trafficking is found to depend directly on glucose partitioning, suggesting that a steady state may support different scenarios. At inhibitory steady state, characterized by high rate of GABA release, there is elevated oxidative activity in astrocyte, not in response to specific energetic needs.

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
David S Liebeskind ◽  
Jose G Romano ◽  
Azhar Nizam ◽  
Edward Feldmann ◽  
Rajbeer S Sangha ◽  
...  

Background: The NINDS-funded Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study used a battery of MRI and TCD techniques to discern key pathophysiology leading to a relatively high rate of recurrent stroke. Our study objectives aimed to relate imaging abnormalities of limited arterial blood flow, distal tissue perfusion and artery-to-artery emboli with new infarcts on 6-8 week MRI. Methods: MyRIAD is a prospective, multicenter, observational study of patients with recent (<21 days) ischemic stroke or TIA due to 50-99% ICAD. Quantitative MRA (QMRA), perfusion MRI and TCD vasomotor reactivity (VMR) with emboli detection (ED) were acquired at enrollment. Central adjudication of each imaging modality, clinical events and 6-8 week MRI were independently ascertained. Results: MyRIAD enrolled 105 (mean age 63.7 years, SD 11.8 years; 43% women) patients. Primary outcomes of recurrent stroke in the territory occurred in 9/105 (9%) with secondary outcomes of territorial TIA in 7/105 (7%) and new infarcts on 6-8 week MRI in 22/87 (25%). The limited number of clinical stroke and TIA endpoints precluded definitive analysis of mechanism. Pre-specified Tmax>4s 10 cc lesions on perfusion MRI were noted in 40/92 (43%) but did not predict new infarcts at 6-8 week MRI. New infarcts were noted in 12/44 (27%) of those with Tmax>4s 5 cc lesions at baseline compared to 3/26 (12%) when absent. Abnormal volume flow ratio (VFR) on QMRA was noted in 25/98 (26%), abnormal TCD VMR in 25/76 (33%) and ED in 30/74 (41%). Other pre-specified analyses revealed both abnormal VMR and ED in 21/77 (27%) and both abnormal Tmax>4s perfusion and VFR in 16/99 (16%). Two or more imaging abnormalities were noted at baseline in 49/105 (47%) and stenosis ≥ 70% in 76/91 (84%). New infarcts on 6-8 week MRI were more frequent with ≥ 2 abnormalities (33 vs 18%, p=0.1) and ≥ 70% stenosis (29 vs 7%, p=0.2). Conclusions: Early, recurrent infarction on MRI is common in ICAD. Imaging abnormalities of limited arterial blood flow or distal tissue perfusion and artery-to-artery emboli are frequent and the presence of multiple abnormalities may increase risk. Larger ICAD studies are needed to link routinely acquired imaging with covert infarcts and cognitive impairment.


2014 ◽  
Vol 925 ◽  
pp. 656-660 ◽  
Author(s):  
Hoi Leong Lee ◽  
Abu Bakar Shahriman ◽  
Siti Khadijah Za'aba ◽  
Khairunizam Wan ◽  
S. Ahmad Roohi ◽  
...  

In most cases, surgical vein bypass or interposition vein grafting was used in both primary management of crush-avulsion amputations and on intervention for rehabilitating the patency of occluded arteries via microvascular surgery. However, surgical revascularization has significant shortcomings, principal among which is the high rate of accelerated thrombosis that develops in arterialised vein graft which renders the vein graft susceptible to acute occlusion and eventually give rise to graft failure. Evaluaion and detection of vein graft failure is essential as that will be the starting point for the clinician to make the diagnosis and safeguard patency of implanted vein graft which would otherwise fail. Unfortunately, most of the available diagnostic and monitoring tools available in the market are expensive, hence not all the hospital, private clinic and others medical centers that fully-equipped with these type of equipments. The objective of this study is to design and develop a low-cost and non-invasive vein graft monitoring prototype that able to provide high accuracy in predicting the vein graft patency and meanwhile providing the short-term monitoring on vein graft right after surgery procedure. Impedance plethysmography (IPG) was employed to measure pulsatile changes in longitudinal impedace to quantify arterial blood flow and pulsatile blood volume. Tetra-polar electrode measurement system was implemented by introduce a constant 1-mA AC current (I) at frequency of 100 kHz in the two outer electrodes. The voltage (V) is measured between the two inner electrodes, and the resulting impedance (Z) is calculated using Ohm’s Law. Arterial blood flow and pulsatile blood volume can then be estimated using impedance related volume conduction equation. By measuring the changes in electrical bioimpedance which can be used to derive important hemodynamic variables, it allows the postoperative graft surveillance and early detection atherosclerosis and thrombosis as well as estimate its severity that leads to the vein graft failure.


2013 ◽  
Vol 275-277 ◽  
pp. 672-676 ◽  
Author(s):  
Yan Jiao Xuan ◽  
Yu Chang ◽  
Bin Gao ◽  
Kai Yun Gu

In this study, a computational fluid dynamics (CFD) study based on a finite element method (FEM) was performed for the human aorta with four different flow time patterns (healthy to full intra-aorta pump support). Fully coupled fluid-solid interaction (FSI) simulation was used to investigate the flow profiles in the aortic arch and its branches where the maximum disturbed and non-uniform flow patterns, and the wall shear stress profiles on the same areas. The blood flow was assumed as a homogeneous, incompressible, and Newtonian fluid flow. Flow across four inlets of aortas was derived from a lumped parameter model (LPM). The inlet flow rate waveforms were divided by different blood assist index (BAI), and were calculated with the physiological information of a heart failure patient.


1985 ◽  
Vol 249 (5) ◽  
pp. R539-R543
Author(s):  
L. P. Reynolds ◽  
C. L. Ferrell ◽  
S. P. Ford

Electromagnetic blood flow transducers and uterine arterial, uterine venous, umbilical venous, fetal femoral arterial, and fetal femoral venous catheters were implanted in 11 cows on day 161 +/- 4 of gestation. Antipyrine (0.66 M) plus NaCl (0.16 M) dissolved in deuterium oxide (D2O), or H2O, was infused at a constant rate into the fetal femoral vein catheter. Concentrations of antipyrine and D2O in uterine arterial and venous blood and antipyrine in fetal arterial and umbilical venous blood, as well as middle uterine arterial blood flow (electromagnetic transducer), were determined. Antipyrine and D2O gave similar estimates (steady-state diffusion method) of gravid uterine blood flow. In addition, the slope of the regression of D2O on antipyrine estimates was not different (P greater than 0.10) from one. Electromagnetic transducers gave estimates of uterine blood flow that were 32-42% of those obtained with steady-state diffusion but were correlated (P less than 0.05) with estimates obtained by use of both antipyrine and D2O. The transplacental clearance rate of antipyrine was similar (per kg placenta) to that observed in ewes. It was suggested that the maternal and fetal microvasculatures of the bovine placenta could have a concurrent arrangement with vascular shunts or maldistribution of flows, as has been suggested for the ewe.


2018 ◽  
Vol 71 (4) ◽  
pp. 163-169
Author(s):  
Eiji Kobayashi ◽  
Shin Enosawa

Abstract: Introduction: Research has made progress in organ fabrication using an extracellular matrix, cell sheets, or organoids. Human liver tissue has been constructed using a 3-dimensional (3D) bioprinter and showed evidence that an in vitro generated liver bud was reformed in a rodent liver model. This study describes the stages of development of rat fetal organs and liver structure and reviews recent progress in liver organoid transplantation. Methods: The authors developed the procedures for creating a transected plane for use in experimental microsurgery in rats. A liver lobe was fixed vertically with gauze and it was ligated with 6-0 silk suture in the cut line; the parenchyma was cut, and major vessels were ligated to create the transected plane. The ligated tissue was carefully resected. Hemostasis was not required and hepatic components remained on the transected plane. The plane was covered by omentum. Results: Using this model, we transplanted fetal liver or a 3D bioprinted liver organoid. This microsurgical method enabled creation of an intact liver parenchyma plane. No bleeding was observed. The transplanted liver components successfully engrafted on the liver. Conclusion: This method may provide an essential environment for growing liver using portal and arterial blood flow.


2013 ◽  
Vol 23 (2) ◽  
Author(s):  
Xenia Descovich ◽  
Giuseppe Pontrelli ◽  
Sauro Succi ◽  
Simone Melchionna ◽  
Manfred Bammer

2012 ◽  
Vol 8 (4) ◽  
pp. 417-423
Author(s):  
Przemysław Korohoda ◽  
Przemysław Sypka ◽  
Jacek A. Pietrzyk

ABSTRACT The paper presents an application of the Lopot-plot, which compares the timeaveraged concentration (TAC) and the time-averaged deviation (TAD) of the weekly dialysis cycle, to comprise the results of intensive computational study. The presented case is based on 420 one-week-cycle simulations to verify the consequences implied by the change of the treatments schedule from nonuniformly to uniformly distributed over the week. The concept of steady state is explained and utilized to obtain periodical runs of the urea concentration. The presented graphs encouragingly indicate the potential of such plots in presenting results of multivariable intensive computations that should be advisably performed during the planning process of hemodialysis treatment.


Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 353
Author(s):  
Jayasree Nair ◽  
Lauren Davidson ◽  
Sylvia Gugino ◽  
Carmon Koenigsknecht ◽  
Justin Helman ◽  
...  

The optimal timing of cord clamping in asphyxia is not known. Our aims were to determine the effect of ventilation (sustained inflation–SI vs. positive pressure ventilation–V) with early (ECC) or delayed cord clamping (DCC) in asphyxiated near-term lambs. We hypothesized that SI with DCC improves gas exchange and hemodynamics in near-term lambs with asphyxial bradycardia. A total of 28 lambs were asphyxiated to a mean blood pressure of 22 mmHg. Lambs were randomized based on the timing of cord clamping (ECC—immediate, DCC—60 s) and mode of initial ventilation into five groups: ECC + V, ECC + SI, DCC, DCC + V and DCC + SI. The magnitude of placental transfusion was assessed using biotinylated RBC. Though an asphyxial bradycardia model, 2–3 lambs in each group were arrested. There was no difference in primary outcomes, the time to reach baseline carotid blood flow (CBF), HR ≥ 100 bpm or MBP ≥ 40 mmHg. SI reduced pulmonary (PBF) and umbilical venous (UV) blood flow without affecting CBF or umbilical arterial blood flow. A significant reduction in PBF with SI persisted for a few minutes after birth. In our model of perinatal asphyxia, an initial SI breath increased airway pressure, and reduced PBF and UV return with an intact cord. Further clinical studies evaluating the timing of cord clamping and ventilation strategy in asphyxiated infants are warranted.


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