Neurology Commons^™

The Lysosomal Ragulator Complex Activates Nlrp3 Inflammasome In Vivo Via Hdac6, Kohei Tsujimoto, Tatsunori Jo, Daiki Nagira, Hachiro Konaka, Jeong Hoon Park, Shin-Ichiro Yoshimura, Akinori Ninomiya, Fuminori Sugihara, Takehiro Hirayama, Eri Itotagawa, Yusei Matsuzaki, Yuki Takaichi, Wataru Aoki, Shotaro Saita, Shuhei Nakamura, Andrea Ballabio, Shigeyuki Nada, Masato Okada, Hyota Takamatsu, Atsushi Kumanogoh

Duncan NRI Faculty and Staff Publications

The cellular activation of the NLRP3 inflammasome is spatiotemporally orchestrated by various organelles, but whether lysosomes contribute to this process remains unclear. Here, we show the vital role of the lysosomal membrane-tethered Ragulator complex in NLRP3 inflammasome activation. Deficiency of Lamtor1, an essential component of the Ragulator complex, abrogated NLRP3 inflammasome activation in murine macrophages and human monocytic cells. Myeloid-specific Lamtor1-deficient mice showed marked attenuation of NLRP3-associated inflammatory disease severity, including LPS-induced sepsis, alum-induced peritonitis, and monosodium urate (MSU)-induced arthritis. Mechanistically, Lamtor1 interacted with both NLRP3 and histone deacetylase 6 (HDAC6). HDAC6 enhances the interaction between Lamtor1 and NLRP3, resulting …

Cissus Quadrangularis (Hadjod) Inhibits Rankl-Induced Osteoclastogenesis And Augments Bone Health In An Estrogen-Deficient Preclinical Model Of Osteoporosis Via Modulating The Host Osteoimmune System, Zaffar Azam, Leena Sapra, Kalpana Baghel, Niharika Sinha, Rajesh K Gupta, Vandana Soni, Chaman Saini, Pradyumna K Mishra, Rupesh K Srivastava

Faculty, Staff and Student Publications

Osteoporosis is a systemic skeletal disease characterised by low bone mineral density (BMD), degeneration of bone micro-architecture, and impaired bone strength. Cissus quadrangularis (CQ), popularly known as Hadjod (bone setter) in Hindi, is a traditional medicinal herb exhibiting osteoprotective potential in various bone diseases, especially osteoporosis and fractures. However, the cellular mechanisms underpinning its direct effect on bone health through altering the host immune system have never been elucidated. In the present study, we interrogated the osteoprotective and immunoporotic (the osteoprotective potential of CQ via modulating the host immune system) potential of CQ in preventing inflammatory bone loss under oestrogen-deficient …

An Intervention Mapping Approach To Developing A Stroke Literacy Video For Recent Stroke Survivors: Development And Usability Study, Mary Carter Denny, Andrea Ancer Leal, Tahani Casameni Montiel, Keona J Wynne, Gabrielle Edquilang, Kim Yen Thi Vu, Farhaan Vahidy, Sean I Savitz, Jennifer Es Beauchamp, Anjail Sharrief

Faculty, Staff and Student Publications

BACKGROUND: Most vascular events after stroke may be prevented by modifying vascular risk factors through medical and behavioral interventions. Stroke literacy-an understanding of stroke symptoms, risk factors, and treatment-likely contributes to vascular risk factor control and in turn stroke recurrence risk. Stroke literacy is the lowest among adults belonging to racial and ethnic minority populations in the United States. Video-based interventions targeting stroke literacy may help acute stroke survivors understand stroke and subsequently reduce the risk of stroke recurrence. However, the failure of prior stroke literacy interventions may be due in part to the fact that the interventions were not …

Repurposing Ms Immunotherapies For Cidp And Other Autoimmune Neuropathies: Unfulfilled Promise Or Efficient Strategy?, Felix Kohle, Marinos Dalakas, Helmar C Lehmann

Department of Neurology Faculty Papers

Despite advances in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other common autoimmune neuropathies (AN), still-many patients with these diseases do not respond satisfactorily to the available treatments. Repurposing of disease-modifying therapies (DMTs) from other autoimmune conditions, particularly multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), is a promising strategy that may accelerate the establishment of novel treatment choices for AN. This approach appears attractive due to homologies in the pathogenesis of these diseases and the extensive post-marketing experience that has been gathered from treating MS and NMOSD patients. The idea is also strengthened by a number …

Fn14-Directed Dart Nanoparticles Selectively Target Neoplastic Cells In Preclinical Models Of Triple-Negative Breast Cancer Brain Metastasis, Christine P Carney, Anshika Kapur, Pavlos Anastasiadis, Rodney M Ritzel, Chixiang Chen, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) patients with brain metastasis (BM) face dismal prognosis due to the limited therapeutic efficacy of the currently available treatment options. We previously demonstrated that paclitaxel-loaded PLGA−PEG nanoparticles (NPs) directed to the Fn14 receptor, termed “DARTs”, are more efficacious than Abraxane—an FDA-approved paclitaxel nanoformulation—following intravenous delivery in a mouse model of TNBC BM. However, the precise basis for this difference was not investigated. Here, we further examine the utility of the DART drug delivery platform in complementary xenograft and syngeneic TNBC BM models. First, we demonstrated that, in comparison to nontargeted NPs, DART NPs exhibit preferential association …

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

Regional Fa Values And Loss Of Consciousness In Mild Traumatic Brain Injury, Alexander Asturias, Thomas Knoblauch, Alan Rodriguez, Cheryl Vanier, Caroline Le Tohic, Brandon Barrett, Michael Eisenberg, Rachelle Gibbert, Lennon Zimmerman, Shaunaq Parikh, Anh Nguyen, Sherwin Azad, Leo Germin, Enrico Fazzini, Travis Snyder

Far West Division GME Research Day 2023

No abstract provided.

A Case Of Thrombolytic Associated Ich In The Setting Of Infective Endocarditis, Priscilla Yan, Lama Al-Khoury

Far West Division GME Research Day 2023

No abstract provided.

Cardiac Tamponade In The Setting Of Severe Sepsis And Adrenal Insufficiency, Ayesha Choudhry, Matthew Cardeiro, Angelina Hong, Adekunle Bamgboye

East Florida Division GME Research Day 2023

Introduction: Pericardial effusions can have various etiologies, including infectious, autoimmune, drug induced, endocrinologic, among others. Cardiac tamponade occurs when large effusions compress the heart and can lead to obstructive shock.

Case Description: A 48-year-old female with a history of hypothyroidism and pituitary adenoma resection presented with subjective fevers and generalized weakness for the past 5 days. She was lethargic with muffled heart sounds on exam. Vitals showed a heart rate 95 beats per minute, blood pressure 63/51, respiratory rate 18 breaths per minute, with normal temperature. Labs on admission were significant for white blood cell count of 11,500/L, hemoglobin 10.8 …

Ticagrelor Plus Aspirin Vs Clopidogrel Plus Aspirin In Mild Non-Cardioembolic Ischemic Stroke: A Protocol Of A Randomized, Controlled, Active Comparator Arm, Outcome Assessor Blind, Feasibility Study, Athena Sharifi-Razavi, Amir Moghadam Ahmadi, Nasim Tabrizi, Razieh Daz

Farber Institute for Neuroscience Staff Papers and Presentations

Background & Objectives: The risk of recurrence after a transient ischemic attack (TIA) or minor stroke is high especially within three months after first event. The aim of study is assessing the efficacy of ticagrelor plus aspirin in reduction of mild non-cardioembolic ischemic stroke or high risk TIA recurrence during first 3 months.

Methods: This is a randomized, controlled, active comparator arm, outcome assessor blind, parallel group, feasibility study design on 90 patients with diagnosis of non-cardioembolic minor ischemic stroke or high risk TIA admitted in Bou-Ali Sina Hospital, Sari, Iran. After meeting all inclusion and exclusion criteria, patients will …

Evaluating Digital Cognitive Biomarkers As A Noninvasive Diagnostic Tool For Alzheimer's Disease: Correlations With Classic Csf Biomarkers, Kasey Corripio

Honors Undergraduate Theses

Alzheimer's Disease (AD) is a neurodegenerative disorder affecting over 35 million people. Early diagnosis and intervention are crucial for improving outcomes. Digital Cognitive Biomarkers (DCBs) offer a promising approach for early detection and disease management, quantifying cognitive processes of encoding and retrieval through a hierarchical Bayesian cognitive processing model using wordlist memory tests. We hypothesize that DCBs will correlate with classic AD cerebrospinal fluid (CSF) biomarkers (Aβ42, T-tau, p-tau) in patients with varying cognitive decline levels compared to healthy elderly controls. Using Alzheimer's Disease Neuroimaging Initiative (ADNI) data and paired Pearson correlation coefficient analysis, our results support the hypothesis, indicating …

Wernicke Encephalopathy: Interplay Between Magnesium And Thiamine, Richard Allen Gorman Ii, Mark Stine, Rafael Vaello, Patrick J. Stocker

West Florida Division GME Research Day 2023

No abstract provided.

Risk Factors For Depression Progression In Parkinson's Disease: A Retrospective Cohort Study, David Kosoy, James Cassuto, Gregory Kurgansky

East Florida Division GME Research Day 2023

Introduction: Depression is a common non-motor symptom in Parkinson's disease (PD) with a significant impact on quality of life and overall prognosis. Despite the availability of effective treatments, many PD patients with depression do not receive timely diagnosis and appropriate intervention. This study aimed to identify risk factors for depression progression in PD to inform clinical practice and future research.

Methods: We conducted a retrospective cohort study of PD patients using registry data from the Parkinson's Progression Markers Initiative (PPMI) dataset. The primary outcome was depression progression, defined as a 2-point or greater increase in the MDS-UPRDS depression score within …

Anti-Nmda Encephalitis In A Patient With Active Covid-19 Infection, Ali Abu-Alya, Janita Sidhu, Hamza Hansoti, Tyler Voss-Hamrick, Venkatachalam Veerappan, Ruhin Sidhu

Far West Division GME Research Day 2023

No abstract provided.

Microvascular Compression Causing Strokes From Subdural Hematoma Treated By Middle Meningeal Artery Embolization, Roy S. Escobar, Ali Abu-Alya, Vishnu Halthore, Julia Collins, Tanvir Khosla, Hamza Hansoti, Janite Sidhu, Venkatachalam Veerappan, Cyndi Tran

Far West Division GME Research Day 2023

No abstract provided.

Case Based Review On Headaches And Cerebral Venous Thromboembolism Post Covid-19 Infection, Aishwarya Raich, Tanvir Khosla, Vishnu Halthore, Ali Abu-Alya, Venkatachalam Veerappan

Far West Division GME Research Day 2023

No abstract provided.

Sudden Onset Ams, Focal Weakness, Fever And Aphasia Due To Intracranial Subdural Empyema In Left Temporo-Parietal Lobe, Lily Hyunjung Lim, Menachem M. Nagar, Pallavi Aneja

East Florida Division GME Research Day 2023

Intracranial subdural empyema (ISE) is a rare infection of brain, which occurs when pus is collectively located in the space between dura and arachnoid matter. In the past, its mortality was nearly 100%, if it was not treated appropriately within 24-48 hours. Thanks to improvement of diagnostic modalities and treatment, its mortality has dramatically decreased. Though, it can still cause a devastating consequence if it is not managed in a timely manner. The common etiology of ISE is different depending on the age group. In younger patients, it occurs frequently as a complication of infection in neighboring structures like sinusitis …

The Role Of The Nlrp3 Inflammasome In Alzheimer's Disease, Ethan S. Terman

UROP Posters

This study examines the consequences of Alzheimer’s in rat and mice test subjects. The goal is to identify the effects of certain NLRP3 inhibiting drugs and to see if there are any noticeable effects in regards to impeding the pathological development of Alzheimer’s disease. The results are visualized by implementing the immunohistochemical process to identify neurodegeneration in the brain and to assess the expression levels of amyloid beta as an indicator of Alzheimer’s pathology. Other tests are also conducted on these transgenic mice to gauge cognitive functioning levels during the onset of their disease, those being behavior tests, but not …

The Kynurenine Pathway In Alzheimer’S Disease: A Meta-Analysis Of Central And Peripheral Levels, Brisa S Fernandes, Mehmet Enes Inam, Nitesh Enduru, Joao Quevedo, Zhongming Zhao

Faculty, Staff and Student Publications

OBJECTIVE: Changes in the kynurenine pathway are recognized in psychiatric disorders, but their role in Alzheimer's disease (AD) is less clear. We aimed to conduct a systematic review and meta-analysis to determine whether tryptophan and kynurenine pathway metabolites are altered in AD.

METHODS: We performed a systematic review and random-effects meta-analyses. Inclusion criteria were studies that compared AD and cognitively normal (CN) groups and assessed tryptophan or kynurenine pathway metabolites in cerebrospinal fluid or peripheral blood.

RESULTS: Twenty-two studies with a total of 1,356 participants (664 with AD and 692 CN individuals) were included. Tryptophan was decreased only in peripheral …