Matching Items (54)

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Development of a Novel Smart Contrast Agent for Magnetic Resonance Imaging

Description

Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize

Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize novel smart contrast agents for MRI that respond to temperature changes in tissue microenvironments. Transmission Electron Microscopy, Nuclear Magnetic Resonance, and cell culture growth assays were used to characterize the physical, magnetic, and cytotoxic properties of candidate nanoprobes. The nanoprobes displayed thermosensitve MR properties with decreasing relaxivity with temperature. Future work will be focused on generating and characterizing photo-active analogues of the nanoprobes that could be used for both treatment of tissues and assessment of therapy.

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Date Created
  • 2014-05

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Novel siloxane nanoprobes for molecular and cellular imagin

Description

Oxygen delivery is crucial for the development of healthy, functional tissue. Low tissue oxygenation, or hypoxia, is a characteristic that is common in many tumors. Hypoxia contributes to tumor malignancy

Oxygen delivery is crucial for the development of healthy, functional tissue. Low tissue oxygenation, or hypoxia, is a characteristic that is common in many tumors. Hypoxia contributes to tumor malignancy and can reduce the success of chemotherapy and radiation treatment. There is a current need to noninvasively measure tumor oxygenation or pO2 in patients to determine a personalized treatment method. This project focuses on creating and characterizing nanoemulsions using a pO2 reporter molecule hexamethyldisiloxane (HMDSO) and its longer chain variants as well as assessing their cytotoxicity. We also explored creating multi-modal (MRI/Fluorescence) nanoemulsions.

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Date Created
  • 2013-05

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Characterization of Inflammatory Cell Population in Brain After SDF-1α Injection

Description

The brain is the most important part of the central nervous system in the human body. It is the center of consciousness and controls all voluntary motor activity of the

The brain is the most important part of the central nervous system in the human body. It is the center of consciousness and controls all voluntary motor activity of the body. Mechanical trauma sustained to the head during a car accident, fall, or sports injury can lead to a traumatic brain injury (TBI) that may have long ranging and sustained physical, cognitive and emotional effects. TBI is the most common form of brain injury and it contributes to one third of all injury related deaths in the United States. The Stabenfeldt lab aims to develop regenerative strategies that will harness inherent endogenous repair mechanisms in traumatic brain injury to improve functional outcomes in cognitive and motor functions. Previous research has demonstrated that the acute inflammatory response after TBI releases soluble cytokines that mediate regeneration after TBI. One of such soluble signal is stromal cell derived factor-1α (SDF-1α) and its receptor CXCR4. The SDF-1α/CXCR4 signaling axis directs the migration and organization of neural progenitor/ stem cells which is important in the regeneration of the injury area. In this study, we probed this paradigm by injecting bolus and nanoparticle exogenous SDF-1α intracortically into mice then sacrificing at 1, 3, and 7 days’ post-injection. Increased CXCR4 positive cells were expressed around the SDF-1α injection area. This study specifically focused on characterizing microglia and macrophage population in the brains that expressed CXCR4 via immunohistochemistry. Data from this study showed that the bolus group initiated microglial activation within the injection tract particularly at day 3 post injection which was resolved by day 7. However, the nanoparticle group initiated the activation of microglial/macrophages as early as day 1 post injection which proceeded to day 7. This shows that the nanoparticle groups initiated an
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inflammatory reaction in the injection tract irrespective of SDF-1α since the blank nanoparticle (nanoparticle with no SDF-1α) group exhibited the identical trend.

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Date Created
  • 2017-05

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Investigating the Effect of a Hyaluronic Acid-Laminin Hydrogel on Inflammation After Traumatic Brain Injury

Description

Traumatic brain injury (TBI) is a leading cause of death in individuals under the age of 45, resulting in over 50,000 deaths each year. Over 80,000 TBI patients report long-term

Traumatic brain injury (TBI) is a leading cause of death in individuals under the age of 45, resulting in over 50,000 deaths each year. Over 80,000 TBI patients report long-term deficits consisting of motor or cognitive dysfunctions due to TBI pathophysiology. The biochemical secondary injury triggers a harmful inflammatory cascade, gliosis, and astrocyte activation surrounding the injury lesion, and no current treatments exist to alleviate these underlying pathologies. In order to mitigate the negative inflammatory effects of the secondary injury, we created a hydrogel comprised of hyaluronic acid (HA) and laminin, and we hypothesized that the anti-inflammatory properties of HA will decrease astrocyte activation and inflammation after TBI. C57/BL6 mice were subjected to mild-to-moderate CCI. Three days following injury, mice were treated with injection of vehicle or HA-Laminin hydrogel. Mice were sacrificed at three and seven days post injection and analyzed for astrocyte and inflammatory responses. In mice treated with vehicle injections, astrocyte activation was significantly increased at three days post-transplantation in the injured cortex and injury lesion. However, mice treated with the HA-Laminin hydrogel experienced significantly reduced acute astrocyte activation at the injury site three days post transplantation. Interestingly, there were no significant differences in astrocyte activation at seven days post treatment in either group. Although the microglial and macrophage response remains to be investigated, our data suggest that the HA-Laminin hydrogel demonstrates potential for TBI therapeutics targeting inflammation, including acute modulation of the astrocyte, microglia, and macrophage response to TBI.

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Date Created
  • 2016-05

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The Effect of Nanoparticle Diameter on TAT-mediated Delivery to the CNS In Vivo

Description

Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain

Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain barrier (BBB). Nanoparticles (NPs) are a promising drug delivery method due to their biocompatibility and ability to be modified by cell penetrating peptides, such as transactivating transciptor (TAT) peptide, which has been shown to increase efficiency of delivery. There are multiple proposed mechanisms of TAT-mediated delivery that also have size restrictions on the molecules that can undergo each BBB crossing mechanism. The effect of nanoparticle size on TAT-mediated delivery in vivo is an important aspect to research in order to better understand the delivery mechanisms and to create more efficient NPs. NPs called FluoSpheres are used because they come in defined diameters unlike polymeric NPs that have a broad distribution of diameters. Both modified and unmodified 100nm and 200nm NPs were able to bypass the BBB and were seen in the brain, spinal cord, liver, and spleen using confocal microscopy and a biodistribution study. Statistically significant differences in delivery rate of the different sized NPs or between TAT-modified and unmodified NPs were not found. Therefore in future work a larger range of diameter size will be evaluated. Also the unmodified NPs will be conjugated with scrambled peptide to ensure that both unmodified and TAT-modified NPs are prepared in identical fashion to better understand the role of size on TAT targeting. Although all the NPs were able to bypass the BBB, future work will hopefully provide a better representation of how NP size effects the rate of TAT-mediated delivery to the CNS.

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Date Created
  • 2016-05

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Enhancing CXCR4 expression of hNPCs using Hyaluronic Acid - Laminin Hydrogel: A Potential Treatment for TBI

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

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.

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Date Created
  • 2016-05

Human Neural Progenitor Cell Adhesion on PDMS Substrates

Description

Abstract
The aim of the research performed was to increase research potential in the field of cell stimulation by developing a method to adhere human neural progenitor cells (hNPC’s) to

Abstract
The aim of the research performed was to increase research potential in the field of cell stimulation by developing a method to adhere human neural progenitor cells (hNPC’s) to a sterilized stretchable microelectrode array (SMEA). The two primary objectives of our research were to develop methods of sterilizing the polydimethylsiloxane (PDMS) substrate being used for the SMEA, and to derive a functional procedure for adhering hNPC’s to the PDMS. The proven method of sterilization was to plasma treat the sample and then soak it in 70% ethanol for one hour. The most successful method for cell adhesion was plasma treating the PDMS, followed by treating the surface of the PDMS with 0.01 mg/mL poly-l-lysine (PLL) and 3 µg/cm2 laminin. The development of these methods was an iterative process; as the methods were tested, any problems found with the method were corrected for the next round of testing until a final method was confirmed. Moving forward, the findings will allow for cell behavior to be researched in a unique fashion to better understand the response of adherent cells to physical stimulation by measuring changes in their electrical activity.

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Date Created
  • 2016-05

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Pharmacologic Modulation of the Blood-Brain Barrier

Description

One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small

One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS. Previous studies have shown that activation of the adenosine receptor signaling pathway through the use of agonists has been demonstrated to increase BBB permeability. For example, regadenoson is an adenosine A2A receptor agonist that has been shown to disrupt the BBB and allow for increased drug uptake in the CNS. The goal of this study was to verify this property of regadenoson. We hypothesized that co-administration of regadenoson with a non-brain penetrant macromolecule would facilitate its entry into the central nervous system. To test this hypothesis, healthy mice were administered regadenoson or saline concomitantly with a fluorescent dextran solution. The brain tissue was either homogenized to measure quantity of fluorescent molecule, or cryosectioned for imaging with confocal fluorescence microscopy. These experiments did not identify any significant difference in the amount of fluorescence detected in the brain after regadenoson treatment. These results contradict those of previous studies and highlight potential differences in injection methodology, time windows, and properties of brain impermeant molecules.

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Date Created
  • 2015-05

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Synthesis of Dual Layered Microparticles for Tunable Delayed Release Profile

Description

The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in

The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA shell surrounding the PLGA core. The microparticles were loaded with bovine serum albumin (BSA) and different volumes of ethanol were added to the PLA shell phase to alter the porosity and release characteristics of the BSA. Different amounts of ethanol varied the total loading percentage of the BSA, the release profile, surface morphology, size distribution, and the localization of the protein within the particles. Scanning electron microscopy images detailed the surface morphology of the different particles. Loading the particles with fluorescently tagged insulin and imaging the particles through confocal microscopy supported the localization of the protein inside the particle. The study suggest that ethanol alters the release characteristics of the loaded BSA encapsulated in the microparticles supporting the use of a polar, protic solvent as a tool for tuning the delayed release profile of biological proteins.

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Date Created
  • 2015-05

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A Novel Temperature-Sensitive MR & Fluorescence Imaging Contrast Agent

Description

Contrast agents in medical imaging can help visualize structural details, distributions of particular cell types, or local environment characteristics. Multi-modal imaging techniques have become increasingly popular for their improved sensitivity,

Contrast agents in medical imaging can help visualize structural details, distributions of particular cell types, or local environment characteristics. Multi-modal imaging techniques have become increasingly popular for their improved sensitivity, resolution, and ability to correlate structural and functional information. This study addresses the development of dual-modality (magnetic resonance/fluorescence) and dual-functional (thermometry/detection) nanoprobes for enhanced tissue imaging.

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Date Created
  • 2015-05