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CHARACTERIZING THE EFFECTS OF MARS MISSION-RELEVANT DOSES OF SPACE RADIATION ON THE GASTROINTESTINAL TRACT

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abstract
Future missions beyond low earth orbit (LEO) will expose astronauts to poorly defined risks of space radiation consisting of solar energetic particles (SEP) and galactic cosmic rays (GCR), including high-energy charge (HZE) nuclei. While GCR HZE flux intensity is relatively low, radiobiological effectiveness can be extremely high. Poor understanding of the biological effects of this unique radiation environment confounds risk assessment. The gastrointestinal (GI) system is one of the most radiosensitive tissues of the body, showing marked sensitivity to both the direct (DNA-damaging) and indirect (inflammation-related) effects of ionizing radiation (IR) exposure. In recent years, we used healthy wild mice, and we exposed them to Mars mission equivalent doses of SEP and GCR radiation. This allowed us to understand the effects of space radiation on the GI system and the innate and adaptive immune response in the GI tract and thereby begin to estimate the risk to an astronaut traveling to Mars. Our data show that exposure to SEP/GCR radiation induces mucosal lesions, apoptosis, extensive RBC extravasation/bleeding, loss of epithelial barrier function, marked lymph node swelling, lymphatic vessel disruption, induction of DNA damage response-related transcripts, and alterations to the intestinal stem cell compartment. We have also found that pre-treatment of the WT mice with novel curcumin-laden nanolipoprotein particles (cNLPs) may provide some degree of protection to the GI system, as evidenced by a significantly reduced expression of IR-responsive gene regulatory networks and in apoptosis. To perform these studies, we used histology, immunohistochemistry (IHC), and gene expression analysis to define, at a functional level, the effects of space radiation on the GI tract during long-term, deep space missions and employed engineering and machine learning to study our murine model small intestines to help analyze these data. It is hoped that our ongoing efforts will better define, and ultimately lead to means of mitigating, the harmful effects of space radiation on the GI system.
subject
contributor
Diaz, Jonathan Harvey (author)
Porada, Christopher CDP (committee chair)
Schwartz, Marshall MZS (committee member)
date
2021-06-03T08:35:41Z (accessioned)
2021 (issued)
degree
Biomedical Engineering (discipline)
2023-06-02 (liftdate)
embargo
2023-06-02 (terms)
identifier
http://hdl.handle.net/10339/98774 (uri)
language
en (iso)
publisher
Wake Forest University
title
CHARACTERIZING THE EFFECTS OF MARS MISSION-RELEVANT DOSES OF SPACE RADIATION ON THE GASTROINTESTINAL TRACT
type
Thesis

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