Browsing by Author "Alshammari, Abdulkarim"

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ANGIOTENSIN II TYPE 2 RECEPTOR AGONIST PREVENTS THE PRO- INFLAMMATORY RESPONSE IN LPS TREATED HUMAN MACROPHAGES
(ProQuest, 2020-08) Alshammari, Abdulkarim; Fagan, Susan
Stroke is a leading cause of long term disability and is associated with a 30% incidence of severe cognitive impairment. Sustained pro-inflammatory microglia activation contributes to, and our lab has shown that the Angiotensin II type 2 receptor (AT2R) agonist, compound 21 (C21), can prevent the development of, PSCI. We hypothesized that activation of pro-inflammatory microglia and macrophages can be prevented with C21. This was assessed using a microglial cell line (C8-B4) and THP-1 derived macrophages. The reduction in the pro- inflammatory cell markers was assessed via RT-qPCR using the following genes, IL-1b, TNFa, and NOS2. Cells were either pre-treated, prior to LPS exposure, or post-treated after LPS treatment, with C21 (100 uM). C21 effectively reduced the expression of IL-1b in a concentration-dependent manner. Both pre- and post- treatment with C21 significantly reduced the expression of pro-inflammatory markers after LPS exposure in a mouse microglial cell line and human macrophages.
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MECHANISMS OF COGNITIVE IMPAIRMENT DEVELOPMENT IN AGED HYPERTENSIVE RATS: FOCUS ON MACROPHAGES
(ProQuest, 2023) Alshammari, Abdulkarim; Fagan, Susan; Zhang, Duo
Stroke survivors have an increased risk of developing long-term disability and dementia. Hypertension and aging are major contributing factors to vascular dementia, stroke, and the development of PSCI. Most animal models fail to capture the complex interplay between these pathophysiologic processes. The purpose of this dissertation is to investigate the impact of aging and hypertension on cognitive function, prior to, and following stroke. We utilized aged hypertensive rats to study the trajectory of vascular cognitive impairment, and to investigate the impact of delayed and chronic stimulation of Angiotensin II type 2 receptor on stroke outcomes. Sixty SHRs were housed (in pairs) for 18 months with cognitive assessments every six months and post-surgery. Multiple MRI scans were performed at baseline and throughout the study. At day 3 after stroke, rats were randomized to receive either an angiotensin receptor agonist, Compound 21, or plain drinking water and followed up for 8 weeks. Additionally, we examined the ability of C21 to mediate anti- inflammatory and neurotrophic effects in mouse microglial cell line, C8-B4, and RAW 264.7 macrophages.
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