Unpredictable solar particle events can pose several health risks to astronauts in space, with the risk becoming greater during missions beyond low-Earth orbit. Dr. Daniela Trani is conducting a study to evaluate the effects radiation has on the intestine. She hypothesizes that intestinal inflammation caused by radiation exposure may contribute, along with systemic response, to the early symptoms of radiation sickness, such as anorexia, nausea and vomiting. The study will assess the potential advantages of anti-inflammatory therapy to treat the prodromal syndrome.
Overview
The Role of Intestinal Inflammation in Acute Effects Induced by Exposure to Protons During Solar Particle Events: A Mouse Model Approach (First Award Fellowship)
Principal Investigator:
Daniela Trani, Ph.D.
Organization:
Georgetown University Medical Center
Technical Summary
Unpredictable, sporadic and large solar particle events (SPEs) pose serious health risks for manned exploratory missions beyond low-Earth orbit. These events acutely could cause the prodromal syndrome – a transient period of anorexia, nausea and vomiting that starts within a few hours of exposure, and may compromise crew performance.
At expected doses, acute effects could be due to direct damage to intestinal mucosa as well as the effect of injury responses that involve intercellular signaling. Ionizing radiation (IR) activates a complex network of stress responses that affect cellular functions and cellular viability, and triggers altered expression of variety of cytokines and other intercellular messengers. Many of these signaling events can impinge on processes associated with inflammatory responses. Many studies show that after IR there is a general over-expression of pro-inflammatory markers systemically and in tissues such as the intestine. A major mediator of inflammatory signaling is p38 MAP kinase (p38), which is upstream, and sometimes downstream, of key cytokines including TNF-α, IL-6 and IL-1ß, as well as other key mediators like COX-2 and p53.
In the case of the prodromal syndrome, inflammatory signaling may have an impact on intestinal function either directly by damage to the mucosa, by local production of inflammatory cytokines, or by systemic effects of inflammatory cytokines on the gut. Our principal hypothesis is that inflammatory signaling contributes to the prodromal syndrome and can affect the gut either by local signaling events and/or by systemic cytokine signaling. We are using a genetic approach in a defined mouse model system to study inflammatory signaling after space radiation exposure with emphasis on SPEs, and the effects of such signaling on cellular and molecular parameters in the intestine. By blocking p38 signaling with dominant-negative p38 mutant, we are able to assess the potential advantages of anti-inflammatory therapy to treat the prodromal syndrome.
Earth Applications
Our principal hypothesis is that inflammatory signaling contributes to the prodromal syndrome following exposure to radiation for therapeutic purposes, or in deep space during long-term missions beyond low-Earth orbit. Radiation-induced inflammation may affect the gut either by local signaling events and/or by systemic cytokine signaling. We are using a genetic approach in a defined mouse model system to study inflammatory signaling after space radiation with emphasis on protons, and the effects of such signaling on cellular and molecular parameters in the intestine. By blocking p38 signaling with a dominant-negative p38 mutant, generated in the laboratory of my mentor, Dr. Albert J. Fornace Jr., our study will contribute to assessing the potential advantages of anti-inflammatory therapies to treat the prodromal syndrome experienced by patients undergoing radiotherapy.
This project's funding ended in 2011