Description:
1. The proposed research will provide molecular information on the effects of age at radiation exposure, time of tissue collection after exposure, and effects of genomic background on dose response and thresholds for Central Nervous System (CNS) pathways associated with radiation-damage response and neuropathology. This information will provide time information on early and late neuro-pathological changes associated with vascular damage and inflammation that will support establishment of acute and late (CNS) Permissible Exposure Limits (PELs). Our research plan will identify low-dose thresholds for the expression of unique molecular changes and changes in pathways associated with neuropathology.
2. The proposed proteomic and metabolomic research results will be used to identify CNS subregion-specific responses as well as common radiation responses, and to identify mouse-rat cross-genome-risk biomarkers and pathways for the development of molecular countermeasures. This research will examine the molecular evidence that common pathways are affected by HZE exposure in three CNS subregions of the same animal in cerebral spinal fluid (CSF), cortex and hippocampus. This research will focus on molecular changes and signaling pathways after low dose exposure, with emphasis on molecular changes associated with vascular damage and inflammation.
The knowledge gained in this research project will (a) provide data to compare low-dose tissue response across brain subregions in two rodent species (rats and mice), (b) provide evidence of dose-dependence and persistence of pathways associated with neurotoxicity (e.g., inflammation, vascular damage) across CNS subregions in two species, and (c) inform identification of CNS biomarkers and mechanism-based radioprotective countermeasures.