Radiation-induced Brain Injury and the Radiation Late Effects Cohort (RLEC) of Rhesus Macaques (Macaca mulatta).

Abstract

In the event of a nuclear accident or attack, thousands of people could receive high doses of total-body irradiation (TBI). Although retrospective analyses of atomic bomb and nuclear disaster survivors have been conducted, the long-term outcomes on the brain and cognitive function are conflicting. Radiation-induced brain injury (RIBI) is characterized by inflammation, vascular injury, deficits in neuronal function, and white matter (WM) injury, but the molecular mechanisms by which this occurs remain unknown. Animal models are crucial for evaluating radiation effects on the brain and have provided significant insight into the pathogenesis of RIBI. Rodents are the most commonly utilized animal models in radiation research, and much has been gleaned from these animals. Non-human primates (NHPs) are the closest genetically, anatomically, and physiologically to humans and therefore represent a valuable resource in translational neuroscience. NHPs have been utilized in radiation studies for several decades and continue to be important models of RIBI, yet few studies have evaluated the long-term impact of radiation on neurocognitive function. The Radiation Late Effects Cohort (RLEC) is a group of rhesus macaques dedicated to evaluating the long-term effects of TBI on multiple systems, including the nervous system. Studies have demonstrated that animals within the RLEC manifest shared patterns of injury between macaques and humans after fractionated whole-brain irradiation (WBI), including vascular injury, neuroinflammation, and WM injury. While pathological outcomes in late-delayed RIBI have been well characterized, studies evaluating the functional outcomes in NHPs are scarce, highlighting the need for future studies. Correlating relevant structural and functional outcomes are critical for identifying targets involved in the pathogenesis of injury. Much information has been gleaned from animal studies of RIBI, and NHPs, particularly those in the RLEC will continue to be valuable models in translational neuroscience.