Task CBS VNSCOR #1: Responses of the Nervous System to Chronic, Low Dose Charged Particle Irradiation
Last Published:  07/31/19 10:05:33 AM (Central)
Short Title: CBS VNSCOR #1 - Radiation Dose Rate Effectiveness Factors (Nelson)
Responsible HRP Element: Human Factors and Behavioral Performance
Collaborating Org(s):
Human Health Countermeasures (HHC) Element
Other:
Space Radiation (SR) Element
Funding Status: Active - Currently funded and in progress
Procurement Mechanism(s):
Solicited
Aims:
Nelson/Davis Virtual NSCOR: The project is an experimental campaign combined with "Mechanisms of Radiation-Induced Neurobehavioral Defictis" (PI: Davis)(see above) to quantify responses for an interrelated set of central nervous system (CNS) outcome measures in mice to acute and protracted exposures to protons at a dose of 0.5 Gy and sham controls; acute and protracted exposures to 0.25 and 0.5 Gy of charged particles, and acute and protracted exposures to 0.5 and 1.5 Gy of gamma rays. All proposed work will use wild type mice and will be performed under IACUC approved protocols in AAALAC-certified facilities at Loma Linda University (LLU), the University of California, Irvine (UCSF) and Brookhaven National Laboratory (BNL). For all three specific aims the species is Mus musculus, strain C57Bl/6J. Ages are 5 - 6 months at acquisition and the beginning of 42 day irradiation procedures. Sexes are males and females. Scheduled euthanasia's are at 1 week, 30 days, 90 days, 6 months and 12 months post-irradiation. Behavioral testing will occur prior to the use of the same animals for terminal assays. All outcome measures will be quantified in males (N=960) and a subset of measures less prone to sex-dependent variability will be quantified in females (N=220) for a total of N = 1180.                                                 
Aim 1: Quantify responses for an interrelated set of CNS outcome measures in mice to acute and protracted exposures to protons at a dose of 0.5 Gy and sham controls. Derive DREFs for the set of outcome measures.
Aim 2: Quantify responses for an interrelated set of CNS outcome measures in mice to acute and protracted exposures to simulated galactic cosmic ray (GCRsim) radiation at doses of 0.25 and 0.5 Gy. Derive DREFs for the set of outcome measures.
Aim 3: Quantify responses for an interrelated set of CNS outcome measures in mice to protracted exposures to 137Cs gamma radiation at doses of 0.75 and 2.0 Gy. Combine results with those of specific aim 2 to determine RBEs for the set of outcome measures for protracted GCRsim exposure.
 
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Mappings
RiskRisk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure
GapCBS-CNS - 1: Are there significant adverse changes in CNS performance in the context and time scale of spaceflight operations? If so, how is significance defined, and which neuropsychological domains are affected? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?
GapCBS-CNS - 2: Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post-flight)?
GapCBS-CNS - 5: How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE?
You are here!TaskCBS VNSCOR #1: Responses of the Nervous System to Chronic, Low Dose Charged Particle Irradiation

RiskRisk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
GapCBS-BMed3: We need to identify and quantify the key threats to and promoters of mission relevant behavioral health and performance during autonomous, long duration and/or long distance exploration missions.
GapCBS-CNS - 1: Are there significant adverse changes in CNS performance in the context and time scale of spaceflight operations? If so, how is significance defined, and which neuropsychological domains are affected? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?
GapCBS-CNS - 2: Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post-flight)?
GapCBS-CNS - 5: How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE?
You are here!TaskCBS VNSCOR #1: Responses of the Nervous System to Chronic, Low Dose Charged Particle Irradiation

RiskRisk of Adverse Health Event Due to Altered Immune Response
You are here!TaskCBS VNSCOR #1: Responses of the Nervous System to Chronic, Low Dose Charged Particle Irradiation

RiskRisk of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure and Secondary Spaceflight Stressors
You are here!TaskCBS VNSCOR #1: Responses of the Nervous System to Chronic, Low Dose Charged Particle Irradiation