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Final Thesis for Submission.pdf (9.53 MB)

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Analyzing consequences to astrocytes in a mouse model of brain arteriovenous malformation

Ward, Brittney M
http://orcid.org/0000-0002-6021-5527
http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1619298440206905

Abstract Details

2021, Bachelor of Science (BS), Ohio University, Neuroscience.
Arteriovenous malformation (AVM) is a disease where the typical connections between arteries and veins are abnormal and enlarged, so blood flows more directly from arteries to veins. These enlarged vessels have compromised integrity and are very susceptible to rupture. Though it only affects 0.01% of the population, AVM accounts for 2% of all strokes. AVM can also cause other issues such as aneurism, migraines, and seizures. Treatments for AVM are limited, in part because of a lack of understanding about how the disease occurs and progresses. This thesis uses a mouse model of AVM that manipulates an important developmental signaling pathway to produce AVM-like abnormal arteriovenous connections. Using such disease models, we can advance our understanding of AVM and of potential treatments for AVM. Astrocytes are cells in the brain that contribute to tissue homeostasis and the blood-brain barrier. When the brain sustains damage or disease, astrocytes undergo changes to react and respond to the injury. These are known as reactive astrocytes. These astrocytes can respond in a myriad of ways. There is currently very little research on astrocytes in brain AVM. Astrocytes play such a vital role in brain homeostasis and repair processes that it would be very clinically relevant to understand how AVM affects them. In this thesis, I sought to determine whether astrocytes are reactive in the mouse model of AVM by testing hypertrophy and proliferation, two characteristics of reactive astrocytes. I also assessed levels of glial fibrillary acidic protein (GFAP) through measuring microscope image area, protein expression, and transcript expression in astrocytes. I also tested for changes in other transcripts that could provide evidence in support of astrocyte reactivity. Astrocyte hypertrophy and proliferation increased in the AVM mutant, as compared to controls, suggesting that astrocytes became reactive during AVM pathogenesis. Cortical and cerebellar tissue area with GFAP-positive astrocytes trended toward increased area; however, this analysis needs higher sample size to be able to draw statistical and biological conclusions. Toward understanding molecular changes to AVM-mutant astrocytes, I isolated an enriched astrocyte population from early postnatal mouse brain. Using these isolated cells, I initiated experiments to assess select transcript levels from control and mutant samples. Preliminary data showed successful amplification of products from Gfap, β-actin, Aldh1L1, and C3 transcripts. These experiments will accelerate our ability to determine gene expression changes in AVM mutant astrocytes, as compared to controls. The work described in this thesis represents a new avenue of brain AVM research in our lab and in the field, to understand consequences to astrocytes during brain AVM.
Corinne Nielsen (Advisor)
62 p.
Biology; Biomedical Research; Developmental Biology; Neurobiology; Neurosciences
arteriovenous malformation, AVM, vascular biology, neuroscience, astrocyte, neurovascular unit, reactive astrocytes, vascular biology

Recommended Citations

Citations

  • Ward, B. M. (2021). Analyzing consequences to astrocytes in a mouse model of brain arteriovenous malformation [Undergraduate thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1619298440206905

    APA Style (7th edition)

  • Ward, Brittney. Analyzing consequences to astrocytes in a mouse model of brain arteriovenous malformation. 2021. Ohio University, Undergraduate thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1619298440206905.

    MLA Style (8th edition)

  • Ward, Brittney. "Analyzing consequences to astrocytes in a mouse model of brain arteriovenous malformation." Undergraduate thesis, Ohio University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1619298440206905

    Chicago Manual of Style (17th edition)

ouhonors1619298440206905
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