Browsing by Subject "Blood flow"

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Association between reduced limb perfusion and muscle spasticity in persons with spinal cord injury
(2010-12) Parmar, Yesha Jayantilal; Griffin, Lisa; Tanaka, Hirofumi
Individuals with spinal cord injury (SCI) demonstrate reduced limb blood flow and muscle spasticity. It is plausible that the accumulation of metabolites, resulting from reduced perfusion, could exacerbate spasticity via activation of fusimotor neurons by Group III and IV afferents. PURPOSE: To determine the association between peripheral blood flow and muscle spasticity in persons with SCI. METHODS: A total of 16 individuals with SCI were classified into high (N=6), low (N=5), and no (N=5) spasticity groups according to their spasticity levels indicated by the modified Ashworth scale scores. Blood flow was measured in femoral and brachial arteries using duplex Doppler ultrasound and was normalized to limb lean mass obtained with dual energy X-ray absorptiometry. RESULTS: There were no significant group differences in age (30.5±4.15, 38.48±4.61, 32.6±4.89 years), time post SCI (8.5±4.2, 12.6±4.74, 6.8±1.66 years), American SCI Association motor scores (39.2±7.78, 59±12.34, 53.4±1.08), or sensory scores (96±22.1, 144.4±13.97, 130±13.8). Femoral artery blood flow, adjusted for limb lean mass, was significantly different (p=0.002) across the three leg spasticity groups (high 76.03±6.44, low 95.12±15.49, no 142.53±10.86 ml/min/kg).Total leg muscle spasticity scores were significantly and negatively correlated with femoral artery blood flow (r=-0.60, p=0.014). There was no significant difference in brachial artery blood flow between the three groups, indicating that the reduction in blood flow was confined to injured limbs and not due to systemic cardiovascular disorder. CONCLUSION: Among SCI patients, whole-leg blood flow is progressively lower in individuals with greater spasticity scores. These results suggest that a reduction in lower limb perfusion, among other factors, plays a significant role in the pathogenesis leading to muscle spasticity after SCI.
Cellular interactions during neural repair
(2022-05) Williamson, Michael Ryan; Drew, Michael R., Ph. D.; Jones, Theresa A.; Dunn, Andrew; Noble, Linda; Monfils, Marie
Injury to the central nervous system induces a limited neural repair response that is causally linked to recovery of function. The goal of this dissertation is to better understand neural repair responses, including how different cell types respond to injury and how cellular interactions shape repair. I investigate repair processes in a mouse model of cortical stroke by applying behavioral, imaging, and genetic techniques. In Chapter 2, I characterize the spatiotemporal dynamics of vascular plasticity following stroke, and its association with restoration of blood flow and behavioral function. I find that stroke instigates a short time window during which vascular plasticity unfolds. This window of vascular plasticity is underpinned by transient activation of pro-angiogenic gene expression programs. The formation of new vessels is associated with the restoration of blood flow to peri-infarct regions, which is in turn associated with behavioral improvement. In Chapter 3, I examine reactive astrocyte responses after stroke and their interaction with vascular plasticity. I find that stroke triggers gene expression and functional changes in reactive astrocytes that enable them to support vascular remodeling and repair. Astrocytes orchestrate multiple aspects of vascular repair, including reorganization of extracellular matrix and pericyte attachment to vessels. Ablating reactive astrocytes results in reduced angiogenesis, prolonged blood flow deficits, increased vascular permeability, and worse functional recovery. In Chapter 4 I investigate the subventricular zone (SVZ) cytogenic response to stroke. I find that cells arising from the SVZ after stroke are predominantly undifferentiated precursors and astrocytes. Arrest of cytogenesis by ablation of neural stem cells or aging reduces behavioral recovery. SVZ cytogenesis provides trophic support via vascular endothelial growth factor (VEGF) that drives effective synaptic and vascular plasticity to improve recovery. Replacement of VEGF in peri-infarct cortex of mice lacking cytogenesis is sufficient to increase dendritic spine and vascular density and enhance recovery. Together, these studies refine our understanding of how different cell types response to injury and how cellular interactions coordinate neural repair.
Computer simulation of blood flow in microvessels and numerical experiments on a cell-free layer
(2007-05) Jee, Sol Keun, 1979-; Moser, Robert deLancey
Simulating blood flow in microvessels is a major challenge because of the numerous blood cells suspended in the blood. Furthermore, red blood cells (RBCs), which constitute 45% of the total blood volume, are highly deformable. RBCs deformation and RBC-RBC interactions determine the complex rheology of the blood. In this research, we simulate the blood flow in periodic two dimensional channels and conduct numerical experiments on the cell-free layer which appears near the wall. We use the boundary integral method and the smooth particle mesh Ewald method to represent the blood flow, and cells are modeled as deformable capsules. In the numerical experiments, we examine four possible mechanisms that may contribute to the cell-free layer: RBC deformation, RBC aggregation, configuration constraint, and the lubrication mechanism. Our simulations correctly represent hemodynamic phenomena such as the blunt velocity profile and the Fåhræus effect. We observed that more deformable RBCs migrate more away from the wall, and, consequently, the thickness of the cell-free layer increases. However, RBC aggregation increased the cell-free layer thickness by only 5%. In the experiment on the configuration constraint, no cell-free "layer" was detected when we removed cells which intersected an artificial constraint in the microvessel. In the last experiment on the lubrication mechanism, the cell-free layer disappeared at a no-shear stress boundary, and the hematocrit profile was similar to that in the constraint test. Therefore, this research clearly shows that the cell-free layer is generated by the lateral migration of deformable RBCs due to the lubrication mechanism.
A Microchip CD4 Counting Method for HIV Monitoring in Resource-Poor Settings
(Public Library of Science, 2005-07-19) Rodriguez, William R; Christodoulides, Nicolaos; Floriano, Pierre N; Graham, Susan; Mohanty, Sanghamitra; Dixon, Meredith; Hsiang, Mina; Peter, Trevor; Zavahir, Shabnam; Thior, Ibou; Romanovicz, Dwight; Bernard, Bruce; Goodey, Adrian P; Walker, Bruce D; McDevitt, John T
Background -- More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. Methods and Findings -- Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. Conclusion -- Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality.
Novel optical techniques for imaging oxygen and other hemodynamic parameters during physiological events
(2010-12) Ponticorvo, Adrien; Dunn, Andrew Kenneth, 1970-; Jones, Theresa; Ress, David; Rylander, Grady; Tunnell, James
This dissertation presents the development and use of a novel optical imaging system capable of monitoring changes in blood flow, oxygenated hemoglobin, deoxygenated hemoglobin, and absolute pO₂ in the brain. There are several imaging modalities capable of monitoring these parameters separately. Laser speckle contrast imaging (LSCI) and multi-spectral reflectance imaging (MSRI) have been used to monitor relative blood flow and hemoglobin changes respectively. Phosphorescence quenching, while not typically used for imaging, is capable of noninvasive measurements of pO₂. Combining these three techniques has led to the development of an imaging system that could ultimately lead to a better understanding of brain physiology. By combining techniques such as LSCI and MSRI, it becomes possible to estimate the cerebral metabolic rate of oxygen (CMRO₂), an important indicator of neuronal function. It is equally important to understand absolute pO₂ levels so that oxygen metabolism can be examined in context. Integrating phosphorescence quenching and a spatial light modulator into the imaging system allowed absolute pO₂ to be simultaneously measured in distinct regions. This new combined system was used to investigate pathophysiological conditions such as cortical spreading depression (CSD) and ischemia. The observed hemodynamic changes associated with these events were largely dictated by baseline oxygen levels and varied significantly in different regions. This finding highlighted the importance of having a system capable of monitoring hemodynamic changes and absolute pO₂ simultaneously while maintaining enough spatial resolution to distinguish the changes in different regions. It was found that animals with low baseline pO₂ were unable to deliver enough oxygen to the brain during events like CSD because of the high metabolic demand. In order for this technique to become more prevalent among researchers, it is essential to make it cost effective and simple to use. This was accomplished by replacing the expensive excitation sources with cheaper light emitting diodes (LEDs) and redesigning the software interface so that it was easier to control the entire device. The final system shows the potential to become a key tool for researchers studying the role of absolute pO₂ and other hemodynamic parameters during pathophysiological conditions such as CSD and ischemia.