Terri Murray | Louisiana Tech University (original) (raw)
Papers by Terri Murray
The quarterly Women in Engineering and Science Luncheons provide focused professional development... more The quarterly Women in Engineering and Science Luncheons provide focused professional development for women faculty and graduate students, while also providing a platform for peer-to-peer and student-to-faculty networking. This session will discuss the structure of the luncheons, the professional development training, the interactive activities, networking, and present assessment findings.
Scientific Reports, 2019
Time course, in vivo imaging of brain cells is crucial to fully understand the progression of sec... more Time course, in vivo imaging of brain cells is crucial to fully understand the progression of secondary cellular damage and recovery in murine models of injury. We have combined high-resolution gradient index lens technology with a model of diffuse axonal injury in rodents to enable repeated visualization of fine features of individual cells in three-dimensional space over several weeks. For example, we recorded changes in morphology in the same axons in the external capsule numerous times over 30 to 60 days, before and after induced traumatic brain injury. We observed the expansion of secondary injury and limited recovery of individual axons in this subcortical white matter tract over time. In another application, changes in microglial activation state were visualized in the penumbra region of mice before and after ischemia induced by middle carotid artery occlusion. The ability to collect a series of high-resolution images of cellular features of the same cells pre- and post-injur...
Frontiers in neuroscience, 2018
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for norma... more Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for normal brain function. It is involved in multiple neuronal activities, including plasticity, information processing, and network synchronization. Abnormal GABA levels result in severe brain disorders and therefore GABA has been the target of a wide range of drug therapeutics. GABA being non-electroactive is challenging to detect in real-time. To date, GABA is detected mainly via microdialysis with a high-performance liquid chromatography (HPLC) system that employs electrochemical (EC) and spectroscopic methodology. However, these systems are bulky and unsuitable for real-time continuous monitoring. As opposed to microdialysis, biosensors are easy to miniaturize and are highly suitable for studies; they selectively oxidize GABA into a secondary electroactive product (usually hydrogen peroxide, HO) in the presence of enzymes, which is then detected by amperometry. Unfortunately, this method req...
Annals of Plastic Surgery, 2002
Activator protein 1 (AP-1) is thought to play an important role in the expression of genes expres... more Activator protein 1 (AP-1) is thought to play an important role in the expression of genes expressed in response to ischemia-reperfusion injury. In this report, the activation of AP-1 in rat skeletal muscle during reperfusion after a 4-hour ischemic period was studied. AP-1 activation displayed a biphasic pattern, showing peak activities at 1 hour after perfusion and from 4 hours to 12 hours after perfusion. Inhibition of AP-1 activation was investigated using a potent nuclear factor kappa B inhibitor, proline dithiocarbamate (Pro-DTC). AP-1 binding activity at 1 hour of reperfusion was significantly reduced (29.0 +/- 10.1% SEM; p < 0.05) after intravenous administration of Pro-DTC (n = 7 animals in each group). Further elucidation of the role of AP-1 is warranted in hopes of developing strategies to reduce the deleterious effects of ischemia-reperfusion injury.
Molecular Pharmacology, Oct 28, 2011
We investigated assembly and function of nicotinic acetylcholine receptors (nAChRs) composed of ␣... more We investigated assembly and function of nicotinic acetylcholine receptors (nAChRs) composed of ␣7 and 2 subunits. We measured optical and electrophysiological properties of wildtype and mutant subunits expressed in cell lines and Xenopus laevis oocytes. Laser scanning confocal microscopy indicated that fluorescently tagged ␣7 and 2 subunits colocalize. Fö rster resonance energy transfer between fluorescently tagged subunits strongly suggested that ␣7 and 2 subunits coassemble. Total internal reflection fluorescence microscopy revealed that assemblies localized to filopodia-like processes of SH-EP1 cells. Gain-of-function ␣7 and 2 subunits confirmed that these subunits coassemble within functional receptors. Moreover, ␣72 nAChRs composed of wild-type subunits or fluorescently tagged subunits had pharmacological properties similar to those of ␣7 nAChRs, although amplitudes of ␣72 nAChRmediated, agonist-evoked currents were generally ϳ2-fold lower than those for ␣7 nAChRs. It is noteworthy that ␣72 nAChRs displayed sensitivity to low concentrations of the antagonist dihydro--erythroidine that was not observed for ␣7 nAChRs at comparable concentrations. In addition, cysteine mutants revealed that the ␣7-2 subunit interface does not bind ligand in a functionally productive manner, partly explaining lower ␣72 nAChR current amplitudes and challenges in identifying the function of native ␣72 nAChRs. On the basis of our findings, we have constructed a model predicting receptor function that is based on stoichiometry and position of 2 subunits within the ␣72 nAChRs.
Frontiers in Neuroscience, 2018
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for norma... more Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for normal brain function. It is involved in multiple neuronal activities, including plasticity, information processing, and network synchronization. Abnormal GABA levels result in severe brain disorders and therefore GABA has been the target of a wide range of drug therapeutics. GABA being non-electroactive is challenging to detect in real-time. To date, GABA is detected mainly via microdialysis with a high-performance liquid chromatography (HPLC) system that employs electrochemical (EC) and spectroscopic methodology. However, these systems are bulky and unsuitable for real-time continuous monitoring. As opposed to microdialysis, biosensors are easy to miniaturize and are highly suitable for in vivo studies; they selectively oxidize GABA into a secondary electroactive product (usually hydrogen peroxide, H 2 O 2) in the presence of enzymes, which is then detected by amperometry. Unfortunately, this method requires a rather cumbersome process with prereactors and relies on externally applied reagents. Here, we report the design and implementation of a GABA microarray probe that operates on a newly conceived principle. It consists of two microbiosensors, one for glutamate (Glu) and one for GABA detection, modified with glutamate oxidase and GABASE enzymes, respectively. By simultaneously measuring and subtracting the H 2 O 2 oxidation currents generated from these microbiosensors, GABA and Glu can be detected continuously in real-time in vitro and ex vivo and without the addition of any externally applied reagents. The detection of GABA by this probe is based upon the in-situ generation of α-ketoglutarate from the Glu oxidation that takes place at the Glu microbiosensor. A GABA sensitivity of 36 ± 2.5 pA µM −1 cm −2 , which is 26-fold higher than reported in the literature, and a limit of detection of 2 ± 0.12 µM were achieved in an in vitro setting. The GABA probe was successfully tested in an adult rat brain slice preparation. These results demonstrate that the developed GABA probe constitutes a novel and powerful neuroscientific tool that could be employed in the future for in vivo longitudinal studies of the combined role of GABA and Glu (a major excitatory neurotransmitter) signaling in brain disorders, such as epilepsy and traumatic brain injury, as well as in preclinical trials of potential therapeutic agents for the treatment of these disorders.
Scientific Reports, 2019
time course, in vivo imaging of brain cells is crucial to fully understand the progression of sec... more time course, in vivo imaging of brain cells is crucial to fully understand the progression of secondary cellular damage and recovery in murine models of injury. We have combined high-resolution gradient index lens technology with a model of diffuse axonal injury in rodents to enable repeated visualization of fine features of individual cells in three-dimensional space over several weeks. For example, we recorded changes in morphology in the same axons in the external capsule numerous times over 30 to 60 days, before and after induced traumatic brain injury. We observed the expansion of secondary injury and limited recovery of individual axons in this subcortical white matter tract over time. In another application, changes in microglial activation state were visualized in the penumbra region of mice before and after ischemia induced by middle carotid artery occlusion. the ability to collect a series of high-resolution images of cellular features of the same cells pre-and post-injury enables a unique opportunity to study the progression of damage, spontaneous healing, and effects of therapeutics in mouse models of neurodegenerative disease and brain injury. Multiphoton microscopy together with promoter-directed expression of fluorescent proteins for cell-type specific labeling has propelled in vivo neuroscience research into previously inaccessible regions of the animal brain. These enabling technologies have been combined with implantable gradient index (GRIN) lenses to extended the reach of multiphoton microscopes from the upper layers of the neocortex into the depths of subcortical structures of the murine brain 1-3. GRIN lenses have been used to observe diverse phenomena, such as the growth of tumors 4 and intracellular calcium dynamics 5. Here, we present a system to use GRIN lenses for imaging progressive, secondary damage after brain injury, such as traumatic brain injury (TBI) and ischemic stroke, in murine models. TBI has an immediate effect on brain tissue, including stretching and shearing injuries of vulnerable neuronal axons resulting in transport disruption or disconnection 6-8. Shortly afterward, a cascade of cellular responses, called secondary injury, occurs that amplifies this initial damage manifold 9-11. Axonal undulations are the first morphological sign of cellular damage. Later, swellings, called varicosities, develop on dendrites and axons. Further, damaged axons can disconnect, forming a larger swelling at the proximal end called a terminal bulb 6-8,12. Ischemic stroke is another brain injury that causes immediate damage, including cell death in the ischemic region. This is followed by inflammation-mediated secondary cellular damage in the surrounding tissue, called the penumbra 13. A hallmark of this inflammation is activation of microglia, the resident immune cells of the central nervous system 14. Morphologically, activated microglia transform from small cells with long ramified processes to cells having short processes with a brushy or ameboid form, which enables their mobility 15. Here, we present the design and use of an implanted small-diameter, high-resolution gradient index (hrGRIN) lens system for longitudinal studies that is optimized to image changes in fine cellular features associated with secondary injury in murine models of TBI and ischemic stroke. This chronically-implanted lens system, for use with multiphoton microscopy, has the temporal resolution to study dynamic events ranging from seconds to months. Using this system, we were able to observe mobile microglia in the penumbra region a day after ischemic stroke and the progression of secondary axonal damage over several weeks after TBI. We describe how to integrate this system with murine models of brain injury, including midline fluid percussion injury (mFPI), a model of diffuse brain injury 16 , and middle carotid artery occlusion, a model of ischemic stroke 17. Pre-injury images, acquired in
The quarterly Women in Engineering and Science Luncheons provide focused professional development... more The quarterly Women in Engineering and Science Luncheons provide focused professional development for women faculty and graduate students, while also providing a platform for peer-to-peer and student-to-faculty networking. This session will discuss the structure of the luncheons, the professional development training, the interactive activities, networking, and present assessment findings.
Scientific Reports, 2019
Time course, in vivo imaging of brain cells is crucial to fully understand the progression of sec... more Time course, in vivo imaging of brain cells is crucial to fully understand the progression of secondary cellular damage and recovery in murine models of injury. We have combined high-resolution gradient index lens technology with a model of diffuse axonal injury in rodents to enable repeated visualization of fine features of individual cells in three-dimensional space over several weeks. For example, we recorded changes in morphology in the same axons in the external capsule numerous times over 30 to 60 days, before and after induced traumatic brain injury. We observed the expansion of secondary injury and limited recovery of individual axons in this subcortical white matter tract over time. In another application, changes in microglial activation state were visualized in the penumbra region of mice before and after ischemia induced by middle carotid artery occlusion. The ability to collect a series of high-resolution images of cellular features of the same cells pre- and post-injur...
Frontiers in neuroscience, 2018
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for norma... more Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for normal brain function. It is involved in multiple neuronal activities, including plasticity, information processing, and network synchronization. Abnormal GABA levels result in severe brain disorders and therefore GABA has been the target of a wide range of drug therapeutics. GABA being non-electroactive is challenging to detect in real-time. To date, GABA is detected mainly via microdialysis with a high-performance liquid chromatography (HPLC) system that employs electrochemical (EC) and spectroscopic methodology. However, these systems are bulky and unsuitable for real-time continuous monitoring. As opposed to microdialysis, biosensors are easy to miniaturize and are highly suitable for studies; they selectively oxidize GABA into a secondary electroactive product (usually hydrogen peroxide, HO) in the presence of enzymes, which is then detected by amperometry. Unfortunately, this method req...
Annals of Plastic Surgery, 2002
Activator protein 1 (AP-1) is thought to play an important role in the expression of genes expres... more Activator protein 1 (AP-1) is thought to play an important role in the expression of genes expressed in response to ischemia-reperfusion injury. In this report, the activation of AP-1 in rat skeletal muscle during reperfusion after a 4-hour ischemic period was studied. AP-1 activation displayed a biphasic pattern, showing peak activities at 1 hour after perfusion and from 4 hours to 12 hours after perfusion. Inhibition of AP-1 activation was investigated using a potent nuclear factor kappa B inhibitor, proline dithiocarbamate (Pro-DTC). AP-1 binding activity at 1 hour of reperfusion was significantly reduced (29.0 +/- 10.1% SEM; p < 0.05) after intravenous administration of Pro-DTC (n = 7 animals in each group). Further elucidation of the role of AP-1 is warranted in hopes of developing strategies to reduce the deleterious effects of ischemia-reperfusion injury.
Molecular Pharmacology, Oct 28, 2011
We investigated assembly and function of nicotinic acetylcholine receptors (nAChRs) composed of ␣... more We investigated assembly and function of nicotinic acetylcholine receptors (nAChRs) composed of ␣7 and 2 subunits. We measured optical and electrophysiological properties of wildtype and mutant subunits expressed in cell lines and Xenopus laevis oocytes. Laser scanning confocal microscopy indicated that fluorescently tagged ␣7 and 2 subunits colocalize. Fö rster resonance energy transfer between fluorescently tagged subunits strongly suggested that ␣7 and 2 subunits coassemble. Total internal reflection fluorescence microscopy revealed that assemblies localized to filopodia-like processes of SH-EP1 cells. Gain-of-function ␣7 and 2 subunits confirmed that these subunits coassemble within functional receptors. Moreover, ␣72 nAChRs composed of wild-type subunits or fluorescently tagged subunits had pharmacological properties similar to those of ␣7 nAChRs, although amplitudes of ␣72 nAChRmediated, agonist-evoked currents were generally ϳ2-fold lower than those for ␣7 nAChRs. It is noteworthy that ␣72 nAChRs displayed sensitivity to low concentrations of the antagonist dihydro--erythroidine that was not observed for ␣7 nAChRs at comparable concentrations. In addition, cysteine mutants revealed that the ␣7-2 subunit interface does not bind ligand in a functionally productive manner, partly explaining lower ␣72 nAChR current amplitudes and challenges in identifying the function of native ␣72 nAChRs. On the basis of our findings, we have constructed a model predicting receptor function that is based on stoichiometry and position of 2 subunits within the ␣72 nAChRs.
Frontiers in Neuroscience, 2018
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for norma... more Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for normal brain function. It is involved in multiple neuronal activities, including plasticity, information processing, and network synchronization. Abnormal GABA levels result in severe brain disorders and therefore GABA has been the target of a wide range of drug therapeutics. GABA being non-electroactive is challenging to detect in real-time. To date, GABA is detected mainly via microdialysis with a high-performance liquid chromatography (HPLC) system that employs electrochemical (EC) and spectroscopic methodology. However, these systems are bulky and unsuitable for real-time continuous monitoring. As opposed to microdialysis, biosensors are easy to miniaturize and are highly suitable for in vivo studies; they selectively oxidize GABA into a secondary electroactive product (usually hydrogen peroxide, H 2 O 2) in the presence of enzymes, which is then detected by amperometry. Unfortunately, this method requires a rather cumbersome process with prereactors and relies on externally applied reagents. Here, we report the design and implementation of a GABA microarray probe that operates on a newly conceived principle. It consists of two microbiosensors, one for glutamate (Glu) and one for GABA detection, modified with glutamate oxidase and GABASE enzymes, respectively. By simultaneously measuring and subtracting the H 2 O 2 oxidation currents generated from these microbiosensors, GABA and Glu can be detected continuously in real-time in vitro and ex vivo and without the addition of any externally applied reagents. The detection of GABA by this probe is based upon the in-situ generation of α-ketoglutarate from the Glu oxidation that takes place at the Glu microbiosensor. A GABA sensitivity of 36 ± 2.5 pA µM −1 cm −2 , which is 26-fold higher than reported in the literature, and a limit of detection of 2 ± 0.12 µM were achieved in an in vitro setting. The GABA probe was successfully tested in an adult rat brain slice preparation. These results demonstrate that the developed GABA probe constitutes a novel and powerful neuroscientific tool that could be employed in the future for in vivo longitudinal studies of the combined role of GABA and Glu (a major excitatory neurotransmitter) signaling in brain disorders, such as epilepsy and traumatic brain injury, as well as in preclinical trials of potential therapeutic agents for the treatment of these disorders.
Scientific Reports, 2019
time course, in vivo imaging of brain cells is crucial to fully understand the progression of sec... more time course, in vivo imaging of brain cells is crucial to fully understand the progression of secondary cellular damage and recovery in murine models of injury. We have combined high-resolution gradient index lens technology with a model of diffuse axonal injury in rodents to enable repeated visualization of fine features of individual cells in three-dimensional space over several weeks. For example, we recorded changes in morphology in the same axons in the external capsule numerous times over 30 to 60 days, before and after induced traumatic brain injury. We observed the expansion of secondary injury and limited recovery of individual axons in this subcortical white matter tract over time. In another application, changes in microglial activation state were visualized in the penumbra region of mice before and after ischemia induced by middle carotid artery occlusion. the ability to collect a series of high-resolution images of cellular features of the same cells pre-and post-injury enables a unique opportunity to study the progression of damage, spontaneous healing, and effects of therapeutics in mouse models of neurodegenerative disease and brain injury. Multiphoton microscopy together with promoter-directed expression of fluorescent proteins for cell-type specific labeling has propelled in vivo neuroscience research into previously inaccessible regions of the animal brain. These enabling technologies have been combined with implantable gradient index (GRIN) lenses to extended the reach of multiphoton microscopes from the upper layers of the neocortex into the depths of subcortical structures of the murine brain 1-3. GRIN lenses have been used to observe diverse phenomena, such as the growth of tumors 4 and intracellular calcium dynamics 5. Here, we present a system to use GRIN lenses for imaging progressive, secondary damage after brain injury, such as traumatic brain injury (TBI) and ischemic stroke, in murine models. TBI has an immediate effect on brain tissue, including stretching and shearing injuries of vulnerable neuronal axons resulting in transport disruption or disconnection 6-8. Shortly afterward, a cascade of cellular responses, called secondary injury, occurs that amplifies this initial damage manifold 9-11. Axonal undulations are the first morphological sign of cellular damage. Later, swellings, called varicosities, develop on dendrites and axons. Further, damaged axons can disconnect, forming a larger swelling at the proximal end called a terminal bulb 6-8,12. Ischemic stroke is another brain injury that causes immediate damage, including cell death in the ischemic region. This is followed by inflammation-mediated secondary cellular damage in the surrounding tissue, called the penumbra 13. A hallmark of this inflammation is activation of microglia, the resident immune cells of the central nervous system 14. Morphologically, activated microglia transform from small cells with long ramified processes to cells having short processes with a brushy or ameboid form, which enables their mobility 15. Here, we present the design and use of an implanted small-diameter, high-resolution gradient index (hrGRIN) lens system for longitudinal studies that is optimized to image changes in fine cellular features associated with secondary injury in murine models of TBI and ischemic stroke. This chronically-implanted lens system, for use with multiphoton microscopy, has the temporal resolution to study dynamic events ranging from seconds to months. Using this system, we were able to observe mobile microglia in the penumbra region a day after ischemic stroke and the progression of secondary axonal damage over several weeks after TBI. We describe how to integrate this system with murine models of brain injury, including midline fluid percussion injury (mFPI), a model of diffuse brain injury 16 , and middle carotid artery occlusion, a model of ischemic stroke 17. Pre-injury images, acquired in