Nervous System Commons^™

Loss Of Sarm1 Affects Myelin Uptake And Clearance In Macrophages, Grace J. Bergeron

Senior Theses

Clearance of myelin debris is an essential step in nerve regeneration after injury in both the central nervous system (CNS) and peripheral nervous system (PNS), a process that is primarily carried out by macrophages. Failure to phagocytose and clear myelin can prolong inflammation and impair recovery. Sterile alpha and TIR motif-containing protein 1 (SARM1) is well researched as a regulator of axonal degeneration, yet its role in macrophages is still unclear. This study investigates how sarm1 deletion and cytokine signaling influence macrophage uptake and clearance of CNS and PNS myelin in vitro. Splenic macrophages isolated from wild-type (WT) and sarm1 …

Bilateral Small Vessel Strokes In A Young Male With Coccidioidal Meningitis And Suspected Cns Vasculitis, Hugo Zamarron, Ahsan Ali

Research Colloquium

Background: Cerebral small vessel strokes in young, otherwise healthy adults without traditional vascular risk factors are rare and warrant further investigation. Central nervous system (CNS) vasculitis is an uncommon etiology that may be triggered by infections, including fungal pathogens. This case is notable for a suspected primary CNS vasculitis manifesting as bilateral deep infarcts in the setting of Coccidioidal meningitis. It highlights the importance of considering fungal infections and vasculitis in the differential diagnosis of stroke in younger patients.

Case Presentation: A 32-year-old previously healthy male presented with fever, headache, and was diagnosed with aseptic meningitis. He was later readmitted …

Peripheral Neuroimmune Mechanisms Of Chronic Back Pain, Aleyah Esther Goins

Biomedical Sciences ETDs

Chronic back pain (CBP) affects 1 in 10 people worldwide, reducing mobility, productivity, and quality of life. Despite its prevalence, non-addictive treatments remain limited due to an incomplete understanding of chronic pain mechanisms. This dissertation examines peripheral neuroimmune interactions in CBP using a urokinase-type plasminogen activator (uPA)-induced mouse model (uPA-CBP). uPA, a pro-inflammatory serine protease, was injected into the L2/L3 lumbar spinous ligament, inducing prolonged mechanical and cold hypersensitivity. Flow cytometry of dorsal root ganglia (DRG) showed increased CD45+CD11b+ myeloid cells in males and CD45+CD3+CD4+ lymphocytes in females. DRG neurons from male uPA-CBP mice exhibited heightened action potential firing. Pharmacological …

Maresin-Like 1 Ameliorates Neuropathology Of Alzheimer's Disease In Brains Of A Transgenic Mouse Model, Pallavi Shrivastava, Yan Lu, Shanchun Su, Yuichi Kobayashi, Yuhai Zhao, Nathan Lien, Abdul-Razak Masoud, Walter J. Lukiw, Song Hong

School of Medicine Faculty Publications

(1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis of Alzheimer's disease (AD); consequently, resolving inflammation is pivotal to the amelioration of AD pathology. This can potentially be achieved by the treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. (2) Methods: Here, we report the histological effects of long-term treatment with an SPM, maresin-like 1 (MarL1), on AD pathogenesis in a transgenic 5xFAD mouse model. (3) Results: MarL1 treatment reduced Aβ overload, curbed the loss of neurons in brains especially cholinergic neurons associated with cleaved-caspase-3-associated apoptotic degeneration, reduced microgliosis and the pro-inflammatory M1 …

Sensory Dysfunction And The Role Of Nrf2 In The Production Of Pain In Chronic Hindlimb Ischemia, Oliver Kitzerow

Theses & Dissertations

Peripheral arterial disease (PAD) is a progressive and debilitating atherothrombotic disorder that is estimated to impact >200 million people worldwide. Higher physical activity levels are associated with better overall survival rates, slower decline of functional capability, and improved quality of life. However, intermittent claudication, pain produced by physical activity, severely limits functional capacity in PAD patients. Despite known sensory dysfunction and documented neuropathy in diseased patients, the neural mechanisms that produce pain in PAD are yet to be identified. Importantly, few animal models of hindlimb ischemia (HLI) successfully recapitulate chronic human PAD. We developed a chronic animal model of HLI …

Effects Of Diet On Lcn2 Expression And Onset Of Neuroinflammation In An Alzheimer’S Disease Mice Model, Abdirahman A. Hayir

Neuroscience Honors Projects

This project covers the findings regarding the impact of diet on lipocalin 2 (LCN2) and the effects it has on neuroinflammation Alzheimer’s Disease (AD). LCN2 is a protein that is critical to the functionality of mitochondria and inflammatory responses. Evidence has shown that mitochondrial dysfunction is a potential central event in driving AD pathogenesis and contributing to formation of pathological hallmarks such as chronic inflammation. Furthermore, studies have shown that LCN2 can be deficient under metabolic conditions such as high-fat-diet (HFD). This study investigates if HFD induces LCN2 deficiency and increased neuroinflammation in an AD mice model.

Neuroinflammation In Alzheimer's Disease And Vascular Cognitive Impairment, Erica M. Weekman

Theses and Dissertations--Physiology

It was once believed that the brain was immunologically privileged with no resident or infiltrating immune cells; however, now it is understood that the cells of the brain are capable of a wide range of inflammatory processes and phenotypes. Inflammation in the brain has been implicated in several disease processes such as Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID); however, the role of inflammation in these two dementias is poorly understood.

When we stimulated a pro-inflammatory phenotype with an adeno-associated viral vector in a transgenic mouse model of AD that develops Aβ plaques, we saw a pro-inflammatory …

Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved In Immunity And Neurogenesis In Simian Immunodeficiency Virus-Infected Macaques, John K Maxi, Matt Dean, Jovanny Zabaleta, Krzysztof Reiss, Gregory J. Bagby, Steve Nelson, Peter J. Winsauer, Francesca Peruzzi, Patricia E. Molina

School of Graduate Studies Faculty Publications

Alcohol use disorders (AUD) exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+) patients. We have shown that chronic binge alcohol (CBA) administration (13-14 g EtOH/kg/wk) prior to and during simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; = 2) macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; = 2) macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 …

Diffuse Brain Injury Triggers Ultra-Rapid Perisomatic Traumatic Axonal Injury, Wallerian Change, And Non-Specific Inflammatory Responses, Brian Joseph Kelley

Theses and Dissertations

A significant component of diffuse brain injury (DBI) is diffuse axonal injury (DAI) which is responsible for the morbidity and mortality associated with this condition. DAI and its experimental counterpart traumatic axonal injury (TAI) result in scattered microscopic pathology characterized by focal impairment of axonal transport leading to progressive swelling and delayed axotomy. DBI-mediated perisomatic axotomy does not result in acute neuronal death suggesting that delayed axotomy was responsible for this unanticipated response. To evaluate this hypothesis, we examined the spatiotemporal progression of DBI-mediated perisomatic TAI. LM / TEM identified impaired axonal transport within 15 - 30 min post-injury. Perisomatic …