Task CBS VNSCOR #1: Responses of the Nervous System to Chronic, Low Dose Charged Particle Irradiation
Last Published:  03/26/21 03:34:00 PM (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
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 Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
GapBMed-101: We need to identify, quantify, and validate the key selection factors for astronaut cognitive and behavioral strengths (e.g., resiliency) and operationally-relevant performance threats for increasingly Earth independent, long-duration, autonomous, and/or long-distance exploration missions.
GapBMed-102: Given exposures to spaceflight hazards (space radiation, isolation), how do we identify individual susceptibility, monitor molecular/biomarkers and acceptable thresholds, and validate behavioral health and CNS/neurological/neuropsychological performance measures and domains of relevance to exploration class missions?
GapBMed-103: What are the validated, efficacious treatments (individual or Team-based) and/or countermeasures to prevent adverse behavioral conditions, CNS/neurological, and/or psychiatric disorders caused by either single and/or integrated exposures to spaceflight hazards during exploration class missions?
GapBMed-107: What are the long-term changes and risks to astronaut health post-mission that, when using a continuity of care model, helps retrospectively identify and understand individual susceptibility (e.g., hereditary, dose, thresholds) to mitigate adverse CNS, cognitive, and behavioral health changes resulting from long-duration exploration missions, promoting the behavioral health of current and future crews?
GapBMed-108: Given each crewmember will experience multiple spaceflight hazards simultaneously, we need to identify and characterize the potential additive, antagonistic, or synergistic impacts of multiple stressors (e.g., space radiation, altered gravity, isolation, altered immune, altered sleep) on crew health and/or CNS/ cognitive functioning to develop threshold limits and validate countermeasures for any identified adverse crew health and/or operationally-relevant performance outcomes.
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 Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight
You are here!TaskCBS VNSCOR #1: Responses of the Nervous System to Chronic, Low Dose Charged Particle Irradiation