Because regional blood flow increases in association with the increased metabolic demand generated by localized increases in neural activity, functional imaging researchers often assume that changes in blood flow are an accurate read-out... more
Because regional blood flow increases in association with the increased metabolic demand generated by localized increases in neural activity, functional imaging researchers often assume that changes in blood flow are an accurate read-out of changes in underlying neural activity. An understanding of the mechanisms that link changes in neural activity to changes in blood flow is crucial for assessing the validity of this assumption, and for understanding the processes that can go wrong during disease states such as ischaemic stroke. Many studies have investigated the mechanisms of neurovascular regulation in arterioles but other evidence suggests that blood flow regulation can also occur in capillaries, because of the presence of contractile cells, pericytes, on the capillary wall. Here we review the evidence that pericytes can modulate capillary diameter in response to neuronal activity and assess the likely importance of neurovascular regulation at the capillary level for functional imaging experiments. We also discuss evidence suggesting that pericytes are particularly sensitive to damage during pathological insults such as ischaemia, Alzheimer's disease and diabetic retinopathy, and consider the potential impact that pericyte dysfunction might have on the development of therapeutic interventions and on the interpretation of functional imaging data in these disorders.
Microvascular stability and regulation of capillary tonus are regulated by pericytes and their interactions with endothelial cells (EC). While the RhoA/Rho kinase (ROCK) pathway has been implicated in modulation of pericyte contractility,... more
Microvascular stability and regulation of capillary tonus are regulated by pericytes and their interactions with endothelial cells (EC). While the RhoA/Rho kinase (ROCK) pathway has been implicated in modulation of pericyte contractility, in part via regulation of the myosin light chain phosphatase (MLCP), the mechanisms linking Rho GTPase activity with actomyosin-based contraction and the cytoskeleton are equivocal. Recently, the myosin phosphatase-RhoA-interacting protein (MRIP) was shown to mediate the RhoA/ROCK-directed MLCP inactivation in vascular smooth muscle. Here we report that MRIP directly interacts with the β-actin-specific capping protein βcap73. Furthermore, manipulation of MRIP expression influences pericyte contractility, with MRIP silencing inducing cytoskeletal remodeling and cellular hypertrophy. MRIP knockdown induces a repositioning of βcap73 from the leading edge to stress fibers; thus MRIP-silenced pericytes increase F-actin-driven cell spreading twofold. The...
The instability of a self-gravitating fluid cylinder surrounded by a self-gravitating tenuous medium pervaded by transverse varying electric field is discussed under the combined effect of the capillary, self-gravitating, and electric... more
The instability of a self-gravitating fluid cylinder surrounded by a self-gravitating tenuous medium pervaded by transverse varying electric field is discussed under the combined effect of the capillary, self-gravitating, and electric forces. This has been done for all axisymmetric and nonaxisymmetric modes of perturbation. The problem is formulated and solved with excluding the singular solutions, and the stability criterion is derived. Several published works are obtained as limiting cases from the present general case and investigated, and moreover the results are interpreted physically. The model is stable due to the stabilizing effect of the transverse electric field in all modes of perturbation. The destabilizing effect of the capillary and self-gravitating forces is found in small domain in the axisymmetric perturbation. However, the stabilizing effects of the capillary and self-gravitating forces in large axisymmetric domains and in all nonaxisymmetric domains modify and imp...
The development and experimental optimization of a novel flow injection-capillary electrophoresis (FI-CE) analyzer employing UV-visible fiber optic detection is described. The analyzer incorporates a miniature charge-coupled device (CCD)... more
The development and experimental optimization of a novel flow injection-capillary electrophoresis (FI-CE) analyzer employing UV-visible fiber optic detection is described. The analyzer incorporates a miniature charge-coupled device (CCD) spectrometer and operates in a graphical programming environment. Data from experimental optimization studies and small molecule separations involving affinity capillary electrophoresis (ACE) and indirect detection of anions are presented. Future directions in terms of instrument automation and incorporation into a microfluidic format are also discussed.
In striated muscle, the number of capillaries containing moving red blood cells increases with increasing metabolic demand. This phenomenon, termed capillary recruitment, has long been recognized but its mechanism has been unclear. Here,... more
In striated muscle, the number of capillaries containing moving red blood cells increases with increasing metabolic demand. This phenomenon, termed capillary recruitment, has long been recognized but its mechanism has been unclear. Here, a theoretical model for metabolic blood flow regulation in a heterogeneous network is used to test the hypothesis that capillary recruitment occurs as a result of active control of arteriolar diameters, combined with unequal partition of hematocrit at diverging microvascular bifurcations. The network structure is derived from published observations of hamster cremaster muscle in control and dilated states. The model for modulation of arteriolar diameters includes length-tension characteristics of vascular smooth muscle and responses of smooth muscle tone to myogenic, shear-dependent, and metabolic stimuli. Blood flow is simulated including non-uniform hematocrit distribution. Convective and diffusive oxygen transport in the network is simulated. Oxy...
Acute kidney injury induces the loss of renal microvessels, but the fate of endothelial cells and the mechanism of potential vascular endothelial growth factor (VEGF)-mediated protection is unknown. Cumulative cell proliferation was... more
Acute kidney injury induces the loss of renal microvessels, but the fate of endothelial cells and the mechanism of potential vascular endothelial growth factor (VEGF)-mediated protection is unknown. Cumulative cell proliferation was analyzed in the kidney of Sprague-Dawley rats following ischemia-reperfusion (I/R) injury by repetitive administration of BrdU (twice daily) and colocalization in endothelial cells with CD31 or cablin. Proliferating endothelial cells were undetectable for up to 2 days following I/R and accounted for only ∼1% of BrdU-positive cells after 7 days. VEGF-121 preserved vascular loss following I/R but did not affect proliferation of endothelial, perivascular cells or tubular cells. Endothelial mesenchymal transition states were identified by localizing endothelial markers (CD31, cablin, or infused tomato lectin) with the fibroblast marker S100A4. Such structures were prominent within 6 h and sustained for at least 7 days following I/R. A Tie-2-cre transgenic cr...
The fluid dynamics video shows three-dimensional experimental and numerical investigations of open channel flows in microgravity. The dynamic reorientation of the free surface from 1g to 0g environment can be observed in a wedge-shaped... more
The fluid dynamics video shows three-dimensional experimental and numerical investigations of open channel flows in microgravity. The dynamic reorientation of the free surface from 1g to 0g environment can be observed in a wedge-shaped channel for subcritical and for supercritical flow rate with a collapse of the interface. In addition three-dimensional computations determine important characteristics of the flow, such as the free surface shape, the velocity field, the dynamics of the reorientation and the flow rate depended collapse of the free surface. The good agreement validates the capabilities of the numerical solver.
Data obtained by capillary electrophoresis with diode array detection (CE-DAD) were modeled with the purpose to discriminate Argentinean white wines samples produced from three grape varieties (Torrontés, Chardonnay, and Sauvignon blanc).... more
Data obtained by capillary electrophoresis with diode array detection (CE-DAD) were modeled with the purpose to discriminate Argentinean white wines samples produced from three grape varieties (Torrontés, Chardonnay, and Sauvignon blanc). Thirty eight samples of commercial white wine from four wine-producing provinces of Argentina (Mendoza, San Juan, Salta, and Rio Negro) were analyzed. CE-DAD matrices with dimensions of 421 elution times (from 1.17 to 7.39 minutes) × 71 wavelengths (from 227 to 367 nm) were joined in a three way data array and decomposed by Tucker3 method under non-negativity constraint, employing 18, 18 and 6 factors in the modes 1, 2 and 3, respectively. Using the scores of Tucker model, it was possible to discriminate samples of Argentinean white wine by linear discriminant analysis and Kernel linear discriminant analysis. Core element analysis of the Tucker3 model allows identifying the loading profiles in spectral mode related to Argentinean white wine samples...