Helena W Morrison

Interests

Teaching

Pathophysiology, Aquired Brain Injury, Neuroinflammation, Glia

Research

Ischemic Stroke, Neuroinflammation, Microglia, Astrocytes, Phagocytosis

Courses

Scholarly Contributions

Journals/Publications

• Ritter, L. S., Matthew, G. J., Rothers, J. L., Morrison, H. W., & DeBoe, J. C. (2022). An Outpatient Transitions of Care Model for Heart Failure. International Journal of Nursing and Heath Care Science, 2(10), 1-7.
• Nguyen, T. V., Crumpacker, R. H., Calderon, K. E., Garcia, F. G., Zbesko, J. C., Frye, J. B., Gonzalez, S., Becktel, D. A., Yang, T., Tavera-Garcia, M. A., Morrison, H. W., Schnellmann, R. G., Longo, F. M., & Doyle, K. P. (2021). Post-stroke administration of the p75 neurotrophin receptor modulator, LM11A-31, attenuates chronic changes in brain metabolism, increases neurotransmitter levels, and improves recovery. The Journal of pharmacology and experimental therapeutics.
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  The aim of this study was to test whether post-stroke oral administration of a small molecule p75 neurotrophin receptor(p75) modulator (LM11A-31) can augment neuronal survival and improve recovery in a mouse model of stroke. Mice were administered LM11A-31 for up to 12 weeks, beginning 1 week after stroke. Metabolomic analysis revealed that after 2 weeks of daily treatment, mice that received LM11A-31 were distinct from vehicle treated mice by principal component analysis and had higher levels of serotonin, acetylcholine, and dopamine in their ipsilateral hemisphere. LM11A-31 treatment also improved redox homeostasis by restoring reduced glutathione. It also offset a stroke induced reduction in glycolysis by increasing acetyl-CoA. There was no effect on cytokine levels in the infarct. At 13 weeks following stroke, adaptive immune cell infiltration in the infarct was unchanged in LM11A-31 treated mice, indicating that LM11A-31 does not alter the chronic inflammatory response to stroke at the site of the infarct. However, LM11A-31 treated mice had less brain atrophy, neurodegeneration, tau pathology, and microglial activation in other regions of the ipsilateral hemisphere. These findings correlated with improved recovery of motor function on a ladder test, improved sensorimotor and cognitive abilities on a nest construction test, and less impulsivity in an open field test. These data support small molecule modulation of the p75 neurotrophin receptor for preserving neuronal health and function during stroke recovery. The findings from this study introduce the p75 neurotrophin receptor as a novel small molecule target for promotion of stroke recovery. Given that LM11A-31 is in clinical trials as a potential therapy for Alzheimer's disease, it could be considered as a candidate for assessment in stroke or vascular dementia studies.
• Pottenger, A. E., Bartlett, M. J., Sherman, S. J., Falk, T., & Morrison, H. W. (2021). Evaluation of microglia in a rodent model of Parkinson's disease primed with L-DOPA after sub-anesthetic ketamine treatment. Neuroscience letters, 765, 136251.
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  Parkinson's disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc), characterized by motor dysfunction. While PD symptoms are well treated with L-DOPA, continuous use can cause L-DOPA-induced dyskinesia (LID). We have previously demonstrated that sub-anesthetic ketamine attenuated LID development in rodents, measured by abnormal involuntary movements (AIMs), and reduced the density of maladaptive striatal dendritic mushroom spines. Microglia may play a role by phagocytosing maladaptive neuronal spines. In this exploratory study, we hypothesized that ketamine would prevent AIMs and change microglia ramified morphology - an indicator of a microglia response. Unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats were primed with daily injections of L-DOPA for 14 days, treated on days 0 and 7 for 10-hours with sub-anesthetic ketamine (i.p.), and we replicated that this attenuated LID development. We further extended our prior work by showing that while ketamine treatment did lead to an increase of striatal interleukin-6 in dyskinetic rats, indicating a modulation of an inflammatory response, it did not change microglia number or morphology in the dyskinetic striatum. Yet an increase of CD68 in the SNpc of 6-OHDA-lesioned hemispheres post-ketamine indicates increased microglia phagocytosis suggestive of a lingering microglial response to 6-OHDA injury in the SNpc pointing to possible anti-inflammatory action in the PD model in addition to anti-dyskinetic action. In conclusion, we provide further support for sub-anesthetic ketamine treatment of LID. The mechanisms of action for ketamine, specifically related to inflammation and microglia phagocytic functions, are emerging, and require further examination.
• Taylor-Piliae, R. E., Morrison, H. W., Hsu, C. P., Whitman, S., & Grandner, M. (2021). The Feasibility of Tai Chi Exercise as a Beneficial Mind-Body Intervention in a Group of Community-Dwelling Stroke Survivors with Symptoms of Depression. Evidence-based complementary and alternative medicine : eCAM, 2021, 8600443.
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  Depression is prevalent among one-third to two-thirds of acute and chronic stroke survivors. Despite the availability of pharmacotherapies and/or psychotherapies, depression persists, even for 5-10 years after stroke, reflecting limited treatment responses and/or adherence to this conventional care. Mind-body interventions are commonly used among adults to ameliorate depressive symptoms. Thus, the feasibility of Tai Chi, alongside conventional care, to manage poststroke depression was investigated using a single-group pre-post intervention design. Recruitment and retention, intervention adherence, safety, acceptability, and fidelity were assessed. Symptoms of depression, anxiety, and stress were assessed using standardized questionnaires, objective sleep was assessed via a research-grade triaxial accelerometer, and blood samples were taken to measure oxidative stress, inflammatory markers, and a neurotrophic growth factor using commercially available kits per manufacturer's protocol. Pre-post intervention changes were assessed using paired -tests. We enrolled stroke survivors ( = 11, mean age = 69.7 ± 9.3) reporting depression symptoms. After the intervention, we observed significant reductions in symptoms of depression (-5.3 ± 5.9, =0.01), anxiety (-2.2 ± 2.4, =0.01), and stress (-4.6 ± 4.8, =0.01), along with better sleep efficiency (+1.8 ± 1.8, =0.01), less wakefulness after sleep onset (-9.3 ± 11.6, =0.04), and less time awake (-9.3 ± 11.6, =0.04). There was a 36% decrease in oxidative stress (=0.02), though no significant changes in the other biomarkers were found (all values >0.05). Tai Chi exercise is a feasible intervention that can be used alongside conventional care to manage poststroke depression, aid in reducing symptoms of anxiety and stress, and improve sleep.
• Young, K. F., Morrison, H. W., Gardner, R., Falk, T., Sariana, V., Bartlett, M. J., Whitman, S. A., Whitman, S. A., Bartlett, M. J., Sariana, V. C., Falk, T., Gardner, R., Morrison, H. W., & Young, K. F. (2021). Can quantifying morphology and TMEM119 expression distinguish between microglia and infiltrating macrophages after ischemic stroke and reperfusion in male and female mice?. Journal of neuroinflammation, 18(1), 58.
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  Ischemic stroke is an acquired brain injury with gender-dependent outcomes. A persistent obstacle in understanding the sex-specific neuroinflammatory contributions to ischemic brain injury is distinguishing between resident microglia and infiltrating macrophages-both phagocytes-and determining cell population-specific contributions to injury evolution and recovery processes. Our purpose was to identify microglial and macrophage populations regulated by ischemic stroke using morphology analysis and the presence of microglia transmembrane protein 119 (TMEM119). Second, we examined sex and menopause differences in microglia/macrophage cell populations after an ischemic stroke.
• May, J. T., Littzen, C. O., Morrison, H. W., & Loescher, L. J. (2020). Experiences of dual PHD-DNP nursing students during doctoral education. Journal of professional nursing : official journal of the American Association of Colleges of Nursing, 36(5), 348-355.
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  Nursing doctoral education now includes an option with a growing national interest: the PhD-DNP dual degree. Although programs have existed for 10 years, little is known about experiences of dual PhD-DNP degree nursing students (DDNS) during doctoral education, including their perceptions of mentorship during coursework, comprehensive exams, and dissertation readiness.
• McGovern, K. E., Cabral, C. M., Morrison, H. W., & Koshy, A. A. (2020). Aging with Toxoplasma gondii results in pathogen clearance, resolution of inflammation, and minimal consequences to learning and memory. Scientific reports, 10(1), 7979.
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  Persistent inflammation has been identified as a contributor to aging-related neurodegenerative disorders such as Alzheimer's disease. Normal aging, in the absence of dementia, also results in gradual cognitive decline and is thought to arise, in part, because of a chronic pro-inflammatory state in the brain. Toxoplasma gondii is an obligate intracellular parasite that establishes a persistent, asymptomatic infection of the central nervous system (CNS) accompanied by a pro-inflammatory immune response in many of its hosts, including humans and rodents. Several studies have suggested that the inflammation generated by certain strains of T. gondii infection can be neuroprotective in the context of a secondary insult like beta-amyloid accumulation or stroke. Given these neuroprotective studies, we hypothesized that a prolonged infection with T. gondii may protect against age-associated decline in cognition. To test this hypothesis, we infected young adult mice with either of two genetically distinct, persistent T. gondii strains (Prugniaud/type II/haplogroup 2 and CEP/type III/haplogroup 3) and monitored mouse weight, survival, and learning and memory over the ensuing 20 months. At the end of the study, we evaluated CNS inflammation and parasite burden in the surviving mice. We found that parasite infection had no impact on age-associated decline in learning and memory and that by 20 months post infection, in the surviving mice, we found no evidence of parasite DNA, cysts, or inflammation in the CNS. In addition, we found that mice infected with type III parasites, which are supposed to be less virulent than the type II parasites, had a lower rate of long-term survival. Collectively, these data indicate that T. gondii may not cause a life-long CNS infection. Rather, parasites are likely slowly cleared from the CNS and infection and parasite clearance neither positively nor negatively impacts learning and memory in aging.
• Beitchman, J. A., Griffiths, D. R., Hur, Y., Ogle, S. B., Bromberg, C. E., Morrison, H. W., Lifshitz, J., Adelson, P. D., & Thomas, T. C. (2019). Experimental Traumatic Brain Injury Induces Chronic Glutamatergic Dysfunction in Amygdala Circuitry Known to Regulate Anxiety-Like Behavior. Frontiers in neuroscience, 13, 1434.
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  Up to 50% of traumatic brain injury (TBI) survivors demonstrate persisting and late-onset anxiety disorders indicative of limbic system dysregulation, yet the pathophysiology underlying the symptoms is unclear. We hypothesize that the development of TBI-induced anxiety-like behavior in an experimental model of TBI is mediated by changes in glutamate neurotransmission within the amygdala. Adult, male Sprague-Dawley rats underwent midline fluid percussion injury or sham surgery. Anxiety-like behavior was assessed at 7 and 28 days post-injury (DPI) followed by assessment of real-time glutamate neurotransmission in the basolateral amygdala (BLA) and central nucleus of the amygdala (CeA) using glutamate-selective microelectrode arrays. The expression of anxiety-like behavior at 28 DPI coincided with decreased evoked glutamate release and slower glutamate clearance in the CeA, not BLA. Numerous factors contribute to the changes in glutamate neurotransmission over time. In two additional animal cohorts, protein levels of glutamatergic transporters (Glt-1 and GLAST) and presynaptic modulators of glutamate release (mGluR2, TrkB, BDNF, and glucocorticoid receptors) were quantified using automated capillary western techniques at 28 DPI. Astrocytosis and microglial activation have been shown to drive maladaptive glutamate signaling and were histologically assessed over 28 DPI. Alterations in glutamate neurotransmission could not be explained by changes in protein levels for glutamate transporters, mGluR2 receptors, astrocytosis, and microglial activation. Presynaptic modulators, BDNF and TrkB, were significantly decreased at 28 DPI in the amygdala. Dysfunction in presynaptic regulation of glutamate neurotransmission may contribute to anxiety-related behavior and serve as a therapeutic target to improve circuit function.
• Morrison, H. W., & Filosa, J. A. (2019). Stroke and the neurovascular unit: glial cells, sex differences, and hypertension. American journal of physiology. Cell physiology, 316(3), C325-C339.
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  A functional neurovascular unit (NVU) is central to meeting the brain's dynamic metabolic needs. Poststroke damage to the NVU within the ipsilateral hemisphere ranges from cell dysfunction to complete cell loss. Thus, understanding poststroke cell-cell communication within the NVU is of critical importance. Loss of coordinated NVU function exacerbates ischemic injury. However, particular cells of the NVU (e.g., astrocytes) and those with ancillary roles (e.g., microglia) also contribute to repair mechanisms. Epidemiological studies support the notion that infarct size and recovery outcomes are heterogeneous and greatly influenced by modifiable and nonmodifiable factors such as sex and the co-morbid condition common to stroke: hypertension. The mechanisms whereby sex and hypertension modulate NVU function are explored, to some extent, in preclinical laboratory studies. We present a review of the NVU in the context of ischemic stroke with a focus on glial contributions to NVU function and dysfunction. We explore the impact of sex and hypertension as modifiable and nonmodifiable risk factors and the underlying cellular mechanisms that may underlie heterogeneous stroke outcomes. Most of the preclinical investigative studies of poststroke NVU dysfunction are carried out primarily in male stroke models lacking underlying co-morbid conditions, which is very different from the human condition. As such, the evolution of translational medicine to target the NVU for improved stroke outcomes remains elusive; however, it is attainable with further research.
• Saber, M., Giordano, K. R., Hur, Y., Ortiz, J. B., Morrison, H., Godbout, J. P., Murphy, S. M., Lifshitz, J., & Rowe, R. K. (2019). Acute peripheral inflammation and post-traumatic sleep differ between sexes after experimental diffuse brain injury. The European journal of neuroscience.
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  Identifying differential responses between sexes following traumatic brain injury (TBI) can elucidate the mechanisms behind disease pathology. Peripheral and central inflammation in the pathophysiology of TBI can increase sleep in male rodents, but this remains untested in females. We hypothesized that diffuse TBI would increase inflammation and sleep in males more so than in females. Diffuse TBI was induced in C57BL/6J mice and serial blood samples were collected (baseline, 1, 5, 7 days post-injury [DPI]) to quantify peripheral immune cell populations and sleep regulatory cytokines. Brains and spleens were harvested at 7DPI to quantify central and peripheral immune cells, respectively. Mixed-effects regression models were used for data analysis. Female TBI mice had 77%-124% higher IL-6 levels than male TBI mice at 1 and 5DPI, whereas IL-1β and TNF-α levels were similar between sexes at all timepoints. Despite baseline sex differences in blood-measured Ly6C monocytes (females had 40% more than males), TBI reduced monocytes by 67% in TBI mice at 1DPI. Male TBI mice had 31%-33% more blood-measured and 31% more spleen-measured Ly6G neutrophils than female TBI mice at 1 and 5DPI, and 7DPI, respectively. Compared with sham, TBI increased sleep in both sexes during the first light and dark cycles. Male TBI mice slept 11%-17% more than female TBI mice, depending on the cycle. Thus, sex and TBI interactions may alter the peripheral inflammation profile and sleep patterns, which might explain discrepancies in disease progression based on sex.
• Rowe, R. K., Harrison, J. L., Morrison, H., Subbian, V., Murphy, S. M., & Lifshitz, J. (2018). Acute post-traumatic sleep may define vulnerability to a second traumatic brain injury in mice. Journal of neurotrauma.
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  Chronic neurological impairments can manifest from repetitive traumatic brain injury (rTBI), particularly when subsequent injuries occur before the initial injury completely heals. Herein, we apply post-traumatic sleep as a physiological biomarker of vulnerability, hypothesizing that a second TBI during post-traumatic sleep worsens neurological and histological outcomes compared to one TBI or a second TBI after post-traumatic sleep subsides. Mice received sham or diffuse TBI by midline fluid percussion injury; brain-injured mice received one TBI or rTBIs at 3hr or 9hr intervals. Over 40 hours post-injury, injured mice slept more than shams. Functional assessments indicated lower latencies on rotarod and increased Neurological Severity Scores for mice with rTBIs within 3-hrs. Anxiety-like behaviors in the open field task were increased for mice with rTBIs at 3hrs. Based on pixel density of silver accumulation, neuropathology was greater at 28 days post-injury (DPI) in rTBI groups than sham and single TBI. Cortical microglia morphology was quantified and mice receiving rTBI were de-ramified at 14 DPI compared to shams and mice receiving a single TBI, suggesting robust microglial response in rTBI groups. Orexin-A positive cells were sustained in the lateral hypothalamus with no loss detected, indicating loss of wake-promoting neurons did not contribute to post-traumatic sleep. Thus, the duration of post-traumatic sleep is a period of vulnerability that results in exacerbated injury from rTBI. Monitoring individual post-traumatic sleep is a potential clinical tool for personalized TBI management, where regular sleep patterns may inform rehabilitative strategies and return-to-activity guidelines.
• Young, K., & Morrison, H. (2018). Quantifying Microglia Morphology from Photomicrographs of Immunohistochemistry Prepared Tissue Using ImageJ. Journal of visualized experiments : JoVE.
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  Microglia are brain phagocytes that participate in brain homeostasis and continuously survey their environment for dysfunction, injury, and disease. As the first responders, microglia have important functions to mitigate neuron and glia dysfunction, and in this process, they undergo a broad range of morphologic changes. Microglia morphologies can be categorized descriptively or, alternatively, can be quantified as a continuous variable for parameters such as cell ramification, complexity, and shape. While methods for quantifying microglia are applied to single cells, few techniques apply to multiple microglia in an entire photomicrograph. The purpose of this method is to quantify multiple and single cells using readily available ImageJ protocols. This protocol is a summary of the steps and ImageJ plugins recommended to convert fluorescence and bright-field photomicrographs into representative binary and skeletonized images and to analyze them using software plugins AnalyzeSkeleton (2D/3D) and FracLac for morphology data collection. The outputs of these plugins summarize cell morphology in terms of process endpoints, junctions, and length as well as complexity, cell shape, and size descriptors. The skeleton analysis protocol described herein is well suited for a regional analysis of multiple microglia within an entire photomicrograph or region of interest (ROI) whereas FracLac provides a complementary individual cell analysis. Combined, the protocol provides an objective, sensitive, and comprehensive assessment tool that can be used to stratify between diverse microglia morphologies present in the healthy and injured brain.
• Morrison, H. W., Young, K., Qureshi, M., Rowe, R., & Lifshitz, J. (2017). Quantitative microglia analyses reveal diverse morphologic responses after diffuse brain injury. Scientific Reports.
• Morrison, H., Young, K., Qureshi, M., Rowe, R. K., & Lifshitz, J. (2017). Quantitative microglia analyses reveal diverse morphologic responses in the rat cortex after diffuse brain injury. Scientific reports, 7(1), 13211.
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  Determining regions of altered brain physiology after diffuse brain injury is challenging. Microglia, brain immune cells with ramified and dynamically moving processes, constantly surveil the parenchyma for dysfunction which, when present, results in a changed morphology. Our purpose was to define the spatiotemporal changes in microglia morphology over 28 days following rat midline fluid percussion injury (mFPI) as a first step in exploiting microglia morphology to reflect altered brain physiology. Microglia morphology was quantified from histological sections using Image J skeleton and fractal analysis procedures at three time points and in three regions post-mFPI: impact site, primary somatosensory cortex barrel field (S1BF), and a remote region. Microglia ramification (process length/cell and endpoints/cell) decreased in the impact and S1BF but not the remote region (p 
• Filosa, J. A., Morrison, H. W., Iddings, J. A., Du, W., & Kim, K. J. (2016). Beyond neurovascular coupling, role of astrocytes in the regulation of vascular tone. Neuroscience, 323, 96-109.
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  The brain possesses two intricate mechanisms that fulfill its continuous metabolic needs: cerebral autoregulation, which ensures constant cerebral blood flow over a wide range of arterial pressures and functional hyperemia, which ensures rapid delivery of oxygen and glucose to active neurons. Over the past decade, a number of important studies have identified astrocytes as key intermediaries in neurovascular coupling (NVC), the mechanism by which active neurons signal blood vessels to change their diameter. Activity-dependent increases in astrocytic Ca(2+) activity are thought to contribute to the release of vasoactive substances that facilitate arteriole vasodilation. A number of vasoactive signals have been identified and their role on vessel caliber assessed both in vitro and in vivo. In this review, we discuss mechanisms implicating astrocytes in NVC-mediated vascular responses, limitations encountered as a result of the challenges in maintaining all the constituents of the neurovascular unit intact and deliberate current controversial findings disputing a main role for astrocytes in NVC. Finally, we briefly discuss the potential role of pericytes and microglia in NVC-mediated processes.
• Morrison, H. W., & Filosa, J. A. (2016). Sex differences in astrocyte and microglia responses immediately following middle cerebral artery occlusion in adult mice. Neuroscience, 339, 85-99.
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  Epidemiological studies report that infarct size is decreased and stroke outcomes are improved in young females when compared to males. However, mechanistic insight is lacking. We posit that sex-specific differences in glial cell functions occurring immediately after ischemic stroke are a source of dichotomous outcomes. In this study we assessed astrocyte Ca(2+) dynamics, aquaporin 4 (AQP4) polarity, S100β expression pattern, as well as, microglia morphology and phagocytic marker CD11b in male and female mice following 60min of middle cerebral artery (MCA) occlusion. We reveal sex differences in the frequency of intracellular astrocyte Ca(2+) elevations (F(1,86)=8.19, P=0.005) and microglia volume (F(1,40)=12.47, P=0.009) immediately following MCA occlusion in acute brain slices. Measured in fixed tissue, AQP4 polarity was disrupted (F(5,86)=3.30, P=0.009) and the area of non-S100β immunoreactivity increased in ipsilateral brain regions after 60min of MCA occlusion (F(5,86)=4.72, P=0.007). However, astrocyte changes were robust in male mice when compared to females. Additional sex differences were discovered regarding microglia phagocytic receptor CD11b. In sham mice, constitutively high CD11b immunofluorescence was observed in females when compared to males (P=0.03). When compared to sham, only male mice exhibited an increase in CD11b immunoreactivity after MCA occlusion (P=0.006). We posit that a sex difference in the presence of constitutive CD11b has a role in determining male and female microglia phagocytic responses to ischemia. Taken together, these findings are critical to understanding potential sex differences in glial physiology as well as stroke pathobiology which are foundational for the development of future sex-specific stroke therapies.
• Morrison, H. W., & Filosa, J. A. (2013). A quantitative spatiotemporal analysis of microglia morphology during ischemic stroke and reperfusion. Journal of neuroinflammation, 10, 4.
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  Microglia cells continuously survey the healthy brain in a ramified morphology and, in response to injury, undergo progressive morphological and functional changes that encompass microglia activation. Although ideally positioned for immediate response to ischemic stroke (IS) and reperfusion, their progressive morphological transformation into activated cells has not been quantified. In addition, it is not well understood if diverse microglia morphologies correlate to diverse microglia functions. As such, the dichotomous nature of these cells continues to confound our understanding of microglia-mediated injury after IS and reperfusion. The purpose of this study was to quantitatively characterize the spatiotemporal pattern of microglia morphology during the evolution of cerebral injury after IS and reperfusion.
• Downs, C. A., & Morrison, H. W. (2011). Beyond the PhD: putting the right tools in your research toolbox. Biological research for nursing, 13(1), 5-14.
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  Postdoctoral training is vital to a successful career for nurse researchers with a biological or biobehavioral focus. Such training provides structured time to devote to gaining substantive knowledge, expanding one's biological-methods repertoire, and writing grants. However, for unknown reasons, relatively few nurses pursue postdoctoral training. A few plausible explanations include a near critical shortage of nursing faculty coupled with an aging population in need of health care, a lack of available mentoring for predoctoral students to pursue postdoctoral training, and the difficulty of navigating the process of finding and choosing the right match for a postdoctoral experience. The purposes of this article are to provide a rationale for choosing postdoctoral training, review common fellowship opportunities, and discuss the process of finding and choosing the right match for postdoctoral training. The authors provide two prospective plans for postdoctoral training and include a plan for staying on track during the postdoctoral experience.
• Morrison, H. W., & Downs, C. A. (2011). Immunological methods for nursing research: from cells to systems. Biological research for nursing, 13(3), 227-34.
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  Scientists and clinicians frequently use immunological methods (IMs) to investigate complex biological phenomena. Commonly used IMs include immunocytochemistry (IC), enzyme-linked immunosorbent assays (ELISA) and flow cytometry. Each of these methodologies exploits a common principle in IMs -the binding of an antibody to its antigen. Scientists continue to develop new methodologies, such as high-throughput immunohistochemistry (IHC) and in vivo imaging techniques, which exploit antibody-antigen binding, to more accurately answer complex research questions involving single cells up to whole organ systems. The purpose of this paper is to discuss established and evolving IMs and to illustrate the application of these methods to nursing research.
• Morrison, H., Frye, J., Davis-Gorman, G., Funk, J., McDonagh, P., Stahl, G., & Ritter, L. (2011). The contribution of mannose binding lectin to reperfusion injury after ischemic stroke. Current neurovascular research, 8(1), 52-63.
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  After complement system (CS) activation, the sequential production of complement products increases cell injury and death through opsonophagocytosis, cytolysis, adaptive, and inflammatory cell responses. These responses potentiate cerebral ischemia-reperfusion (IR) injury after ischemic stroke and reperfusion. Activation of the CS via mannose binding lectin (MBL)-initiated lectin pathway is known to increase tissue damage in response to IR in muscle, myocardium and intestine tissue. In contrast, the contribution of this pathway to cerebral IR injury, a neutrophil-mediated event, is less clear. Therefore, we investigated the potential protective role of MBL deficiency in neutrophil-mediated cerebral injury after IR. Using an intraluminal filament method, neutrophil activation and cerebral injury were compared between MBL-deficient and wild type C57Bl/6 mice subjected to 60 minutes of MCA ischemia and reperfusion. Systemic neutrophil activation was not decreased in MBL-deficient animals after IR. In MBL-deficient animals, cerebral injury was significantly decreased only in the striatum (p < 0.05). Despite MBL deficiency, C3 depositions were evident in the injured hemisphere during reperfusion. These results indicate that while MBL deficiency results in a modest protection of a sub-cortical brain region during IR, redundant complement pathway activation may overwhelm further beneficial effects of MBL deficiency during reperfusion.
• Morrison, H., McKee, D., & Ritter, L. (2011). Systemic neutrophil activation in a mouse model of ischemic stroke and reperfusion. Biological research for nursing, 13(2), 154-63.
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  As a natural response to injury and disease, neutrophils activate, adhere to the microvasculature, migrate into brain tissue, and release toxic substances such as reactive oxygen species and proteases. This neutrophil response occurs when blood flow is returned to brain tissue (reperfusion) after ischemic stroke. Thus, the presence of activated systemic neutrophils increases the potential for tissue injury during reperfusion after ischemic stroke. Although experiments in rat models suggest that activated neutrophils play a pivotal role in cerebral ischemia reperfusion injury, little is known about systemic neutrophil activation during reperfusion following ischemic stroke in a mouse model. The purpose of this study was to characterize systemic leukocyte responses and neutrophil CD11b expression 15-min and 24-hr post-reperfusion in a mouse model of ischemic stroke. The intraluminal filament method of transient middle cerebral artery occlusion (tMCAO) with reperfusion or a sham procedure was performed in male C57Bl/6 mice. Automated leukocyte counts and manual white blood cell (WBC) differential counts were measured. Flow cytometry was used to assess systemic neutrophil surface CD11b expression. The data suggest that the damaging potential of systemic neutrophil activation begins as early as 15 min and remains evident at 24 hr after the initiation of reperfusion. In addition, because transgenic mouse models, bred on a C57Bl/6 background, are increasingly used to elucidate single mechanisms of reperfusion injury after ischemic stroke, findings from this study are foundational for future investigations examining the damaging potential of neutrophil responses post-reperfusion after ischemic stroke in genetically altered mouse models within this background strain.
• Ritter, L., Davidson, L., Henry, M., Davis-Gorman, G., Morrison, H., Frye, J. B., Cohen, Z., Chandler, S., McDonagh, P., & Funk, J. L. (2011). Exaggerated neutrophil-mediated reperfusion injury after ischemic stroke in a rodent model of type 2 diabetes. Microcirculation (New York, N.Y. : 1994), 18(7), 552-61.
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  We tested the hypothesis that both chronic and acute inflammatory processes contribute to worse reperfusion injury and stroke outcome in an experimental model of T2DM.

Presentations

• Morrison, H. W., Falk, T., Pottenter, A. E., Bartlett, M. J., Bartlett, M. J., Pottenter, A. E., Falk, T., & Morrison, H. W. (2020, April). Ketamine’s Effects to Improve Dyskinesia in a Model of Parkinson’s Disease. Western Institute of Nursing: 53rd Annual Communicating Nursing Research Conference. Portland, OR.
• Ozols, A. A., Marballi, K. K., Beck, K. L., Morrison, H. W., & Gallitano, A. L. (2021, September 9th). The immediate early gene EGR3 is required for Trem2 expression. Arizona Alzheimer's Consortium 2020 Annual Scientific Conference. University of Arizona, Tucson AZ: Arizona Alzheimer's Consortium.
• Morrison, H. W., May, J., Littzen, C., & Loescher, L. (2019, Fall). MENTORING EXPERIENCED BY DUAL DOCTORAL DEGREE (PHD-DNP) NURSING STUDENTS. Western Institute of Nursing Research Conference.
• Morrison, H. W., May, J., Littzen, C., & Loescher, L. J. (2019, Fall). Experiences of PhD-DNP dual degree nursing students prior to doctoral candidacy. AACN Doctoral Education Conference.
• Morrison, H. W. (2016, April). Biomarkers of brain injury in Model systems of ischemic stroke. In: Meeting the Biomarker Challenge: Omics, Model Systems and Translational Research (Chair).. Western Institute of Nursing 49th Annual Communicating Research Conference. Anaheim, CA.
• Morrison, H. W. (2016, October). Sex and menopause differences in microglia phagocytosis after ischemic stroke. Translational Neurotrauma Research Program Seminar Series. Phoenix.
• Morrison, H. W. (2015, November). Differences in microglia immune function and stroke outcomes as a function of sex and post-menopause in a mouse model of ischemic stroke.. In Cardiovascular and Stroke Nursing 2015 Early Stage Investigatory Proposal Meeting Session. American Heart Association National Conference. Orlando, FL.

Poster Presentations

• Falk, T., Heien, M. L., Polt, R. L., Streicher, J. M., Madhavan, L., Sherman, S. J., Szabò, L., Apostol, C. R., Molnar, G., Liu, C., Bartlett, M. J., Morrison, H. W., Lujan, A., & Bernard, K. (2021, Fall). Evaluation of a systemically delivered PACAP glycopeptide as a neuroprotective agent in 2 rodent models of Parkinson’s Disease.. Society for Neuroscience Meeting.
• Stopera, C., Bartlett, M. J., Bernard, K., Sexauer, M. R., Esqueda, A., Morrison, H. W., Sherman, S. J., & Falk, T. (2021, January). Behavioral analysis in the progressive unilateral 6-OHDA-lesion rat model indicate a neuroprotective effect of sub-anesthetic ketamine-treatment.. Society for Neuroscience Global Connectome Conference.
• Stopera, C., Bartlett, M. J., Sexauer, M. R., Bernard, K., Stancati, J., Sherman, S. J., Steece-Collier, K., Morrison, H. W., & Falk, T. (2021, November). Analysis of neuroprotective and anti-inflammatory activity of sub-anesthetic ketamine-treatment in the progressive unilateral 6-OHDA-lesion rat model.. Society for Neuroscience Meeting.
• Taylor-Piliae, R. E., Morrison, H. W., Hsu, C., & Grandner, M. (2021, Summer). Changes in Symptoms, Sleep, Oxidative Stress, and Inflammatory Markers Among Community-Dwelling Stroke Survivors After a Tai Chi Exercise Intervention.. European Society of Cardiology, EuroHeartCare 2021 Congress. online presentation due to COVID-19.
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  (Abstract selected for Press Release). Taylor-Piliae, R.E., Morrison, H., Hsu, C.H., Grandner, M. (2021). Changes in Symptoms, Sleep, Oxidative Stress, and Inflammatory Markers Among Community-Dwelling Stroke Survivors After a Tai Chi Exercise Intervention. European Journal of Cardiovascular Nursing, Volume 20, Issue Supplement_1, July 2021, zvab060.075, https://doi.org/10.1093/eurjcn/zvab060.075
• Giordano, K., Ortiz, J. B., Saber, M., Hur, Y., Lifshitz, J., Morrison, H. W., & Rowe, R. (2019, June). Microglia elimination recovers peripheral inflammation-induced sleep but prolongs TBI-induced sleep in mice. National Neurotrauma Society. Pittsburgh.
• Morrison, H. W., Pottenger, A. E., & Falk, T. (2018, November). Evaluating the effects of sub-anesthetic ketamine on microglia morphology in a pre-clinical model of L-Dopa induced dyskinesia.. Society for Neuroscience. San Diego, CA.
• Morrison, H. W., & Young, K. F. (2018, November). Spatial and sex differences in microglia responses after ischemic stroke in mice: evaluating morphology, phagocytosis and IBA1(+)/TMEM119(-) cells. Society for Neuroscience. San Diego.
• Morrison, H. W., Falk, T., Bartlett, M. J., & Pottenger, A. E. (2018, Fall). Evaluating the effects of Sub-Anesthetic Ketamine on Microglia Morphology in a Pre-Clinical Model of L-DOPA-Induced Dyskinesia. Society for Neuroscience Meeting.
• Morrison, H. W., Falk, T., Bartlett, M. J., & Pottenger, A. E. (2018, Fall). Evaluating the effects of Sub-Anesthetic Ketamine on Microglia Morphology in a Pre-Clinical Model of L-DOPA-Induced Dyskinesia. Society for Neuroscience.
• Bartlett, M. J., Flores, A. J., Dollish, H. K., Doyle, K., Pottinger, A., Morrison, H. W., Sherman, S. J., & Falk, T. (2017, December). Neuroplastic effects contribute to the suppression of L-DOPA-induced dyskineasis by sub-anesthetic ketamine. Neurobiology, Aging, Dementias and Movement Disorders Division Meeting. Scottsdale, Arizona: Arizona Wellbeing Commons Division.
• Giordano, K. R., Young, K., Akhter, M., Morrison, H. W., Lifshitz, J., & Rachel, R. K. (2017, July). Secondary Neuropathology and Inflammation Affect Cerebellar Function Following Diffuse Traumatic Brain Injury. National Neuroscience Society. Snowbird, UT.
• Morrison, H. W., Law, L. M., Thomas, T. C., & Lifshitz, J. (2017, July). Neuropathology of the Hippocampal Memory Circuitry in the Days Following Experimental Diffuse Brain Injury. National Neurotrauma Society. Snowbird, UT.
• Morrison, H. W., Young, K., & Salguero, S. (2017, March). SECOND PLACE AWARD!! Sex differences in microglia morphology, complement receptor 3 subunits (CD11b/CD18), and cytokines in the adult healthy brain among male, female, and post-menopause model mice. 12th annual Frontiers in Immunobiology and Immunopathogenesis Symposium 2017. Tucson, Bio5: Department of Immunobiology.
• Salguero, S., Young, K., & Morrison, H. W. (2017, March). SECOND PLACE AWARD!! Methods to Quantify Diverse Microglia Morphologies in the Healthy and Injured Brain. WAESO Student Conference.
• Young, K., Castaneda, S., Ritchie, J., & Morrison, H. W. (2017, June). The importance of sex, cycle and ovarian function in the healthy mouse brain: microglia morphology, complement receptor 3, and cytokines. Neuroinflammation: Concepts, Characteristics, Consequences. Keystone, CO: Keystone Symposia on Molecular and Cellular Biology.
• Morrison, H. W., Iniguez, D., & Craig, Z. (2016, January). The Effects of Dibutyl Phthalate (DBP) on Brain Neuroinflammation.. UBRP conference. Tucson, AZ.
• Morrison, H. W., Young, K., & Salguero, S. (2016, November). Sex differences in microglia morphology, phagocytic marker CD11b, and cytokines in the adult healthy brain among male, female and post-menopause model mice.. Society for Neuroscience. San Diego.
• Morrison, H. W., Young, K., Qureshi, M., & Johnathan, L. (2016, November). Computer-aided skeleton analysis of microglia de-ramification after experimental diffuse brain injury. Society for Neuroscience. San Diego.