Radiation Diminishes Microglial Proliferation in Response to Injury

Science Center, Bent Corridor

Radiation therapy is commonly used to treat cancerous brain tumors. It damages the DNA of cells, preventing them from dividing. It is very effective at killing malignant cells and preventing tumors from growing, however, it also affects healthy brain tissue. Clinicians must balance the negative side effects with the benefits when administering radiation.It is important to understand how radiation disrupts normal, healthy brain function in order to make the best decisions in treating patients. One aspect of brain function that may be disrupted by radiation is the response to injury. Microglia, the resident macrophages of the brain are key mediators of this response and proliferate in response to injury. To test the hypothesis that radiation impairs the brain’s ability to heal injury by impairing microglial proliferation, we used a mouse model. Mice received a clinically relevant dose of radiation, 20 Gy, to the head only, followed three days later by a traumatic (needle) injury to the cortical gray matter. Another three days later, mice received an injection of bromodeoxyuridine (BrdU; 75 mg/ml) to label dividing cells and were euthanized 2 hours later. Fixed brain tissue was cut perpendicular to the needle injury and stained with antibodies to BrdU and P2y12R to identify proliferating microglia. Unfortunately, accurate counts of BrdU+ cells on many of the slides could not be obtained due to issues with staining. The average number of BrdU+ cells in the irradiated tissue was 9.5 (per section), and the average in the unirradiated was 39.8. However, only two irradiated animals produced slides with BrdU staining effective enough to clearly count BrdU+ cells, so this data is inconclusive, but does suggest that the irradiated animals had fewer BrdU+ cells around the injury site. Replicating this experiment, possibly using different antibodies is necessary to confirm these findings