Matching Items (26)
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- All Subjects: Traumatic Brain Injury
- All Subjects: Neuroscience
- Creators: Harrington Bioengineering Program
Description
Traumatic brain injury (TBI) may result in numerous pathologies that cannot currently be mitigated by clinical interventions. Stem cell therapies are widely researched to address TBI-related pathologies with limited success in pre-clinical models due to limitations in transplant survival rates. To address this issue, the use of tissue engineered scaffolds as a delivery mechanism has been explored to improve survival and engraftment rates. Previous work with hyaluronic acid \u2014 laminin (HA-Lm) gels found high viability and engraftment rates of mouse fetal derived neural progenitor/stem cells (NPSCs) cultured on the gel. Furthermore, NPSCs exposed to the HA-Lm gels exhibit increased expression of CXCR4, a critical surface receptor that promotes cell migration. We hypothesized that culturing hNPCs on the HA-Lm gel would increase CXCR4 expression, and thus enhance their ability to migrate into sites of tissue damage. In order to test this hypothesis, we designed gel scaffolds with mechanical properties that were optimized to match that of the natural extracellular matrix. A live/dead assay showed that hNPCs preferred the gel with this optimized formulation, compared to a stiffer gel that was used in the CXCR4 expression experiment. We found that there may be increased CXCR4 expression of hNPCs plated on the HA-Lm gel after 24 hours, indicating that HA-Lm gels may provide a valuable scaffold to support viability and migration of hNPCs to the injury site. Future studies aimed at verifying increased CXCR4 expression of hNPCs cultured on HA-Lm gels are necessary to determine if HA-Lm gels can provide a beneficial scaffold for stem cell engraftment therapy for treating TBI.
ContributorsHemphill, Kathryn Elizabeth (Author) / Stabenfeldt, Sarah (Thesis director) / Brafman, David (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
It is unknown which regions of the brain are most or least active for golfers during a peak performance state (Flow State or "The Zone") on the putting green. To address this issue, electroencephalographic (EEG) recordings were taken on 10 elite golfers while they performed a putting drill consisting of hitting nine putts spaced uniformly around a hole each five feet away. Data was collected at three time periods, before, during and after the putt. Galvanic Skin Response (GSR) measurements were also recorded on each subject. Three of the subjects performed a visualization of the same putting drill and their brain waves and GSR were recorded and then compared with their actual performance of the drill. EEG data in the Theta (4 \u2014 7 Hz) bandwidth and Alpha (7 \u2014 13 Hz) bandwidth in 11 different locations across the head were analyzed. Relative power spectrum was used to quantify the data. From the results, it was found that there is a higher magnitude of power in both the theta and alpha bandwidths for a missed putt in comparison to a made putt (p<0.05). It was also found that there is a higher average power in the right hemisphere for made putts. There was not a higher power in the occipital region of the brain nor was there a lower power level in the frontal cortical region during made putts. The hypothesis that there would be a difference between the means of the power level in performance compared to visualization techniques was also supported.
ContributorsCarpenter, Andrea (Co-author) / Hool, Nicholas (Co-author) / Muthuswamy, Jitendran (Thesis director) / Crews, Debbie (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
DescriptionMy main goal for my thesis is in conjunction with the research I started in the summer of 2010 regarding the creation of a TBI continuous-time sensor. Such goals include: characterizing the proteins in sensing targets while immobilized, while free in solution, and while in free solution in the blood.
ContributorsHaselwood, Brittney (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Cook, Curtiss (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2011-12
Description
The endogenous response of neural stem cell/progenitor (NPSC) recruitment to the brain injury environment following a traumatic brain injury (TBI) is currently under heavy investigation. Mechanisms controlling NPSC proliferation and migration to the brain injury environment remain unclear; however, it is thought that the vascular extracellular matrix proteins (e.g. laminin, fibronectin, and vitronectin) and vascular endothelial growth factor (VEGF) play a role in mediating NPSC behavior through vasophillic interactions. This project attempts to uncover potential VEGF-ECM crosstalk in mediating migration and proliferation. To investigate migration, neurospheres were seeded on ECM-coated wells supplemented with VEGF and without VEGF, and neural outgrowth was measured at days 0, 1, 3, and 8 using differential interference contrast microscopy. Furthermore, single-cell NPSCs were seeded on ECM-coated Transwell membranes with VEGF supplemented media on one side and without VEGF to look at chemotactic migration. Migrated NPSCs were visualized with DAPI nuclear stain and imaged with an inverted fluorescent microscope. To investigate NPSC proliferation, NPSCs were seeded on ECM coated plates as in the radial migration assay and visualized with EdU on day 8. Total proliferation was measured by seeding NPSCs on ECM coated 96-well plates and incubating them with MTT on days 3 and 6. Proliferation was measured using a spectrophotometer at 630nm and 570nm wavelengths. It was found that VEGF-laminin crosstalk synergistically increased radial migration, but may not play a role in chemotactic migration. Understanding the mechanisms behind VEGF-laminin crosstalk in NPSC proliferation and migration may provide crucial information for the design of stem cell transplantation therapies in the future.
ContributorsMillar-Haskell, Catherine Susan (Author) / Stabenfeldt, Sarah (Thesis director) / Addington, Caroline (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
Prior expectations can bias evaluative judgments of sensory information. We show that information about a performer's status can bias the evaluation of musical stimuli, reflected by differential activity of the ventromedial prefrontal cortex (vmPFC). Moreover, we demonstrate that decreased susceptibility to this confirmation bias is (a) accompanied by the recruitment of and (b) correlated with the white-matter structure of the executive control network, particularly related to the dorsolateral prefrontal cortex (dlPFC). By using long-duration musical stimuli, we were able to track the initial biasing, subsequent perception, and ultimate evaluation of the stimuli, examining the full evolution of these biases over time. Our findings confirm the persistence of confirmation bias effects even when ample opportunity exists to gather information about true stimulus quality, and underline the importance of executive control in reducing bias.
ContributorsAydogan, Goekhan (Co-author, Committee member) / Flaig, Nicole (Co-author) / Larg, Edward W. (Co-author) / Margulis, Elizabeth Hellmuth (Co-author) / McClure, Samuel (Co-author, Thesis director) / Nagishetty Ravi, Srekar Krishna (Co-author) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
In this paper, β-estradiol was characterized utilizing electrochemical impedance spectroscopy (EIS) techniques for the purpose of developing a multi-marker fertility sensor. β-estradiol was immobilized onto the surface of gold disk electrodes to find the optimal binding frequency of estradiol and its respective antibody, anti-17β-estradiol, which was determined to be 37.46Hz. At this frequency a logarithmic relationship between concentration and impedance (Z/ohm) was established creating a concentration calibration curve with a slope of 211 ohm/ln(pg mL-1), an R-squared value of 0.986 and a lower limit of detection of 742 fg mL-1. The specificity and cross-reactivity of the antibody with other hormones was tested through interferent and non-target experiments. Signal-to-noise ratio analysis verified that anti-17β-estradiol exhibited minimal chemical reactions with other hormones (SNR< 3) in non-target experiments. Additionally, there were minimal changes in the amount of signal collected during interferent testing, with albumin and follicle stimulating hormone having SNR values greater than 3. These results, along with the unique frequency response of the antibody-target binding reaction, allow for the possibility of using anti-17β-estradiol and β-estradiol for detecting multiple fertility biomarkers on a single sensor.
ContributorsSmith, Victoria Ann (Author) / LaBelle, Jeffrey (Thesis director) / Spano, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Diabetes mellitus is a disease characterized by many chronic and acute conditions. With the prevalence and cost quickly increasing, we seek to improve on the current standard of care and create a rapid, label free sensor for glycated albumin (GA) index using electrochemical impedance spectroscopy (EIS). The antibody, anti-HA, was fixed to gold electrodes and a sine wave of sweeping frequencies was induced with a range of HA, GA, and GA with HA concentrations. Each frequency in the impedance sweep was analyzed for highest response and R-squared value. The frequency with both factors optimized is specific for both the antibody-antigen binding interactions with HA and GA and was determined to be 1476 Hz and 1.18 Hz respectively in purified solutions. The correlation slope between the impedance response and concentration for albumin (0 \u2014 5400 mg/dL of albumin) was determined to be 72.28 ohm/ln(mg/dL) with an R-square value of 0.89 with a 2.27 lower limit of detection. The correlation slope between the impedance response and concentration for glycated albumin (0 \u2014 108 mg/dL) was determined to be -876.96 ohm/ln(mg/dL) with an R-squared value of 0.70 with a 0.92 mg/dL lower limit of detection (LLD). The above data confirms that EIS offers a new method of GA detection by providing unique correlation with albumin as well as glycated albumin. The unique frequency response of GA and HA allows for modulation of alternating current signals so that several other markers important in the management of diabetes could be measured with a single sensor. Future work will be necessary to establish multimarker sensing on one electrode.
ContributorsEusebio, Francis Ang (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Currently, the management of diabetes mellitus (DM) involves the monitoring of only blood glucose using self-monitoring blood glucose devices (SMBGs) followed by taking interventional steps, if needed. To increase the amount of information that diabetics can have to base DM care decisions off of, the development of an insulin biosensor is explored. Such a biosensor incorporates electrochemical impedance spectroscopy (EIS) to ensure an extremely sensitive platform. Additionally, anti-insulin antibody was immobilized onto the surface of a gold disk working electrode to ensure a highly specific sensing platform as well. EIS measurements were completed with a 5mV sine wave that was swept through the frequency spectrum of 100 kHz to 1 Hz on concentrations of insulin ranging from 0 pM to 100 μM. The frequency at which the interaction between insulin and its antibody was optimized was determined by finding out at which frequency the R2 and slope of the impedance-concentration plot were best. This frequency, otherwise known as the optimal binding frequency, was determined to be 459 Hz. Three separate electrodes were developed and the impedance data for each concentration measured at 459 Hz was averaged and plotted against the LOG (pM insulin) to construct the calibration curve. The response was calculated to be 263.64 ohms/LOG(pM insulin) with an R2 value of 0.89. Additionally, the average RSD was determined to be 19.24% and the LLD was calculated to be 8.47 pM, which is well below the physiological normal range. These results highlight the potential success of developing commercial point-of-care insulin biosensors or multi-marker devices operating with integrated insulin detection.
ContributorsDecke, Zachary William (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Cook, Curtiss (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Description
The main objective of this research is to develop and characterize a targeted contrast agent that will recognize acute neural injury pathology (i.e. fibrin) after traumatic brain injury (TBI). Single chain fragment variable antibodies (scFv) that bind specifically to fibrin have been produced and purified. DSPE-PEG micelles have been produced and the scFv has been conjugated to the surface of the micelles; this nanoparticle system will be used to overcome limitations in diagnosing TBI. The binding and imaging properties will be analyzed in the future to determine functionality of the nanoparticle system in vivo.
ContributorsRumbo, Kailey Michelle (Author) / Stabenfeldt, Sarah (Thesis director) / Kodibagkar, Vikram (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
In epilepsy, malformations that cause seizures often require surgery. The purpose of this research is to join forces with the Multi-Center Epilepsy Lesion Detection (MELD) project at University College London (UCL) in order to improve the process of detecting lesions in patients with drug-resistant epilepsy. This, in turn, will improve surgical outcomes via more structured surgical planning. It is a global effort, with more than 20 sites across 5 continents. The targeted populations for this study include patients whose epilepsy stems from Focal Cortical Dysplasia. Focal Cortical Dysplasia is an abnormality of cortical development, and causes most of the drug-resistant epilepsy. Currently, the creators of MELD have developed a set of protocols which wrap various
commands designed to streamline post-processing of MRI images. Using this partnership, the Applied Neuroscience and Technology Lab at PCH has been able to complete production of a post-processing pipeline which integrates locally sourced smoothing techniques to help identify lesions in patients with evidence of Focal Cortical Dysplasia. The end result is a system in which a patient with epilepsy may experience more successful post-surgical results due to the
combination of a lesion detection mechanism and the radiologist using their trained eye in the presurgical stages. As one of the main points of this work is the global aspect of it, Barrett thesis funding was dedicated for a trip to London in order to network with other MELD project collaborators. This was a successful trip for the project as a whole in addition to this particular thesis. The ability to troubleshoot problems with one another in a room full of subject matter
experts allowed for a high level of discussion and learning. Future work includes implementing machine learning approaches which consider all morphometry parameters simultaneously.
commands designed to streamline post-processing of MRI images. Using this partnership, the Applied Neuroscience and Technology Lab at PCH has been able to complete production of a post-processing pipeline which integrates locally sourced smoothing techniques to help identify lesions in patients with evidence of Focal Cortical Dysplasia. The end result is a system in which a patient with epilepsy may experience more successful post-surgical results due to the
combination of a lesion detection mechanism and the radiologist using their trained eye in the presurgical stages. As one of the main points of this work is the global aspect of it, Barrett thesis funding was dedicated for a trip to London in order to network with other MELD project collaborators. This was a successful trip for the project as a whole in addition to this particular thesis. The ability to troubleshoot problems with one another in a room full of subject matter
experts allowed for a high level of discussion and learning. Future work includes implementing machine learning approaches which consider all morphometry parameters simultaneously.
ContributorsHumphreys, Zachary William (Author) / Kodibagkar, Vikram (Thesis director) / Foldes, Stephen (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05