Medicine and Health Sciences Commons^™

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations & Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Mcp-1 Release Modulation Through Interaction Of Pulmonary Endothelial Cells And Mesenchymal Stromal Cells, Kaavya Giridhar

Dissertations & Theses (Open Access)

Background: Ischemic stroke is a leading cause of death and long-term disability

around the world. Current treatment options are limited to the administration of

tissue plasminogen activator (tPA) and/or endovascular therapy, administered within

a limited time window. However, cell-based therapies such as mesenchymal stromal

cells (MSCs) have increasingly shown great promise for ischemic stroke recovery

with some therapies already in various stages of clinical trials. Intravenous (IV)

administration of the MSCs leads to the entrapment of these MSCs in the lungs.

These entrapped MSCs interact with the pulmonary endothelial cells (PECs) and

could modulate the immune response through the release …

The Effect Of Meditation On Stroke-Survivor Resilience: Secondary Analysis Of Existing Data, Mary Love

Dissertations & Theses (Open Access)

Purpose: To test the effect of meditation on resilience of community-dwelling stroke survivors, and to identify resilience predictor variables in these survivors.

Methods: Sub-study with secondary analysis of existing data from the parent study, MEditatioN for post stroke Depression (MEND). Paired samples t-test was used to evaluate the effect of meditation on resilience of stroke-survivors (n=20) in the intervention group. Bivariate analysis and general linear modeling (GLM) were used to identify demographic, clinical, and psychological predictor variables of baseline resilience for all stroke survivors (n=34).

Results: The increase in stroke-survivor resilience scores from baseline (mean 3.46, SD=.81) to intervention completion …

The Role Of Perivascular Fibrosis In Post-Stroke Glymphatic Impairment And Cerebral Amyloid Angiopathy, Matthew D. Howe

Dissertations & Theses (Open Access)

In healthy brain tissue, toxic amyloid-β (Aβ) proteins are transported by the pulsatile flow of cerebrospinal fluid (CSF) along perivascular drainage pathways. Ischemic stroke may disrupt this process, leading to a perivascular build-up of Aβ, termed cerebral amyloid angiopathy (CAA). I hypothesize that an abnormal pattern of extracellular matrix deposition within the vascular basement membrane, termed fibrosis, impairs Aβ drainage from the aged brain after stroke. I further hypothesize that inhibition of astrocytic transforming growth factor-β (TGF-β) signaling can reverse these phenotypes. Finally, I also hypothesize that serum biomarkers of perivascular fibrosis can be used to diagnose CAA following intracerebral …

Modeling Post Stroke Respiratory Dysfunction, Apneas And Cognitive Decline, Anthony Patrizz

Dissertations & Theses (Open Access)

Modeling Post Stroke Respiratory Dysfunction,

Apneas and Cognitive Decline

Anthony Patrizz, B.A.

Advisory Professor: Louise McCullough M.D., Ph.D.

Stroke is a major cause of mortality and the leading cause of long-term disability in the US. More than 60% of individuals suffering a first time stroke develop respiratory dysfunction, prolonging recovery and increasing mortality. Post-stroke cognitive decline is a major contributor to disability and nursing home placement, therefore the cognitive consequences of Stroke Induced Respiratory Dysfunction (SIRD) need to be explored if we hope to enhance functional recovery. The first step towards treatment of the negative consequences of SIRD is the …

Experiences Of Stress And Coping Over Time By Caregivers Of Stroke Survivors: A Mixed-Methods Approach, Fang Ye

Dissertations & Theses (Open Access)

Background/ Objectives: Caregivers of stroke survivors often experience physical and mental stress, decreased physical and emotional well-being, high burden of care, social isolation, and neglecting self-care. The majority of previous research studies have identified caregiver experiences during the first one-to-two years post stroke. Little is known about caregiver experiences beyond the first two years of the post- stroke recovery trajectory, indicating a need for longitudinal study of their experiences over time. Therefore, the objectives of this study were to 1) investigate caregiver experiences of stress and coping over 5-7 years post stroke using quantitative methods, and 2) explore through …

Information Processing Speed Impairment After Stroke, A Descriptive Study, Susan Alderman

Dissertations & Theses (Open Access)

Background Information processing speed (IPS) is an elemental cognitive function impacting multiple other functions including memory, attention, and executive function, and academic skills like arithmetic, reading and writing. However, little research has been done on IPS impairment in acute stroke. This article compares the frequency and severity of IPS impairment in mild and moderate stroke and its impact on quality of life.

Methods The longitudinal study of patients with mild stroke (NIHSS

Results Using linear mixed model regression, similar frequency and severity of IPS and memory impairments were noted, regardless of stroke severity, in the sample of 30 patients (60% …

Characterization Of The Vascular Pathology In The Acta2 R258c Mouse Model And Cerebrovascular Characterization Of The Acta2 Null Mouse, Carlos A. Villamizar

Dissertations & Theses (Open Access)

Mutations in ACTA2, the gene encoding for smooth muscle α-actin, predispose patients to a wide range of vascular diseases and is most commonly associated with thoracic aortic aneurysms (TAAD) and dissections (TAAD) and strokes. TAAD in patients is characterized by aortic media degeneration and loss in contractile force generation followed by aortic enlargement and subsequent rupture. Most stroke cases associated with ACTA2 are described as moyamoya-like cerebrovascular incidents characterized by distal occlusion of the internal carotid artery, stenosis of arteries in the Circle of Willis, and straightening of cerebral arteries. Patient samples are scarcely available for analysis, and the few …