Exposure to high-energy radiation can irreversibly damage nerve cells, and Dr. Marcelo E. Vazquez is studying whether damage to brain cells will cause progressive deterioration of brain function. After exposing mice to radiation, Dr. Vazquez is performing a series of tests to reveal altered behaviors and is looking at neurochemical and structural changes in the brain. The research will lead to defining the neurological risks of radiation exposures and developing countermeasures to protect brain cells after radiation exposure.
Overview
Risk Assessment and Chemoprevention of HZE-Induced CNS Damage
Principal Investigator:
Marcelo E. Vazquez, M.D., Ph.D.
Organization:
Brookhaven National Laboratory
Technical Summary
Because successful operations in space depend on the performance capabilities of astronauts, radiation-induced neurological damage could jeopardize the successful completion of mission requirements as well as have long-term consequences on the health of astronauts. It is therefore necessary to understand the nature of this risk in order to assess its seriousness and to develop countermeasures.
Compared to the large literature associated with radiation therapy, knowledge is limited about the cellular and molecular responses of cells to high-LET HZE radiation in general, and very limited about the central nervous system (CNS) specifically. Therefore, we will compare the effects of charged-particles (Fe, Si), protons, gamma and X-ray radiation on the cells of the CNS, namely neurons and glial (astrocytes and oligodendrocytes). Cell cultures of CNS cells, both cycling and post-mitotic differentiated cells, will be utilized as model systems. We will test the hypothesis that exposure to low fluences/doses of heavy ions and protons can induce cell death in CNS neural cells and that increasingly dense ionizing radiation will be increasingly toxic.
The activation of two separate stress signal transduction pathways will be examined (p53 and ceramide) for their role in causing cell death or other deleterious changes caused by irradiation. And with respect to p53, we will determine which of the post-translational modifications in regulating p53 function are relevant for charged particle-induced cell death. Finally, we will test the hypothesis that modulating the stress signal transduction pathways will modify the radiation response of brain cells exposed to heavy ions and protons, and test the efficacy of several compounds as potential countermeasures for HZE radiation toxicity.
This project's funding ended in 2006