Material Type  

 학위논문

 

0016931984

Date and Time of Latest Transaction  

20240214100357

ISBN  

9798379649548

DDC  

612

Author  

Hernandez, Victoria Guadalupe.

Title/Author  

Translatome Analysis Reveals Microglia and Astrocytes to be Distinct Regulators of Inflammation in the Hyperacute and Acute Phases After Stroke - [electronic resource]

Publish Info  

[S.l.] : Stanford University., 2023

Publish Info  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Material Info  

1 online resource(81 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 84-12, Section: A.

General Note  

Advisor: Wyss-Coray, Tony;Buckwalter, Marion.

학위논문주기  

Thesis (Ph.D.)--Stanford University, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Abstracts/Etc  

요약Ischemic stroke is a leading cause of death and long-term disability. Neuroinflammation after stroke can significantly affect stroke outcomes-it can clear dead tissue and aid neuroplasticity but also exacerbate cell death. However, the exact astrocytic and microglial signaling pathways initiating neuroinflammation after stroke are unresolved and will be critical for developing immunomodulatory stroke therapies. In Chapter 1, I give background on the progression of stroke, status quo of treatments, and the genetic tools used to profile gene expression changes in microglia and astrocytes. Furthermore, I lay out the key gaps in knowledge and give an overview of how this dissertation fills those gaps. In Chapter 2, to parse the astrocytic and microglial response from that of infiltrating cells in the brain after stroke, we used the RiboTag technique to separately obtain astrocyte and microglia-derived transcriptional responses. By crossing floxed RiboTag mice with Aldh1l1- CreER or Cx3cr1-CreER mice, we tagged astrocytic or microglial ribosomes, respectively, and then isolated cell-specific mRNA from ribosomes immunoprecipitated from brain tissue. We performed RNA-sequencing on astrocyte or microglia-specific transcripts obtained from peristroke cortex in male and female mice 4 hours and 3 days after distal middle cerebral artery occlusion or sham surgery. Few sex differences were observed. Microglia initiated a rapid response to stroke at 4 hours by adopting a proinflammatory profile associated with the recruitment of immune cells while the astrocyte profile was dominated by stress response, as well as proinflammatory genes. By 3 days, microglia have dampened their inflammatory response in exchange for a proliferative, phagocytic state. At this timepoint, astrocytes have enhanced their pro-inflammatory response and may be doing this through transcriptional regulation. Taken together this data comprehensively describes the astrocyte and microgliaspecific translatome response in the hyperacute and acute period after stroke and identifies pathways critical for initiating neuroinflammation. Chapter 3 summarizes the findings, provides additional discussion, and comments on future directions to be taken.

Subject Added Entry-Topical Term  

Gender differences.

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Neurodegeneration.

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Cells.

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Gene expression.

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Stroke.

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Blood-brain barrier.

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Dementia.

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Cytokines.

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Medical research.

Subject Added Entry-Topical Term  

Clinical trials.

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Brain.

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Neurosciences.

Subject Added Entry-Topical Term  

Inflammation.

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Flow cytometry.

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Libraries.

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Apoptosis.

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Ischemia.

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Animal cognition.

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Drug dosages.

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Transcription factors.

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Aging.

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Behavioral sciences.

Subject Added Entry-Topical Term  

Bioinformatics.

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Cellular biology.

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Gender studies.

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Genetics.

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Gerontology.

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Immunology.

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Medicine.

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Pharmaceutical sciences.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 84-12A.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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소장사항  

202402 2024

Control Number  

joongbu:640530