A Biological Explanation for Memory Dysfunction after Cranial Radiation

Michelle Monje, MD, PhD, of the Department of Neurology at BWH and Massachusetts General Hospital, and Keith Ligon, MD, PhD, of the Department of Pathology at BWH and Children’s Hospital Boston, report in an advanced online Annals of Neurology article a biological explanation for memory dysfunction after cranial radiation for central nervous system (CNS) malignancies such as medulloblastoma and leukaemia.

This study confirms, in humans, previous animal research that found a clinically relevant dose of cranial radiation destroys the process of generating new neurons (neurogenesis) in the memory centre of the brain (hippocampus), therefore impairing normal memory function. In these previous animal studies, Monje demonstrated that cranial radiation induced brain inflammation, thereby altering the stem cell environment and preventing the cells from generating new neurons. Treatment with anti-inflammatory drugs partially restored neurogenesis in animals after radiation.In the current study, Monje and Ligon examined hippocampal brain tissue from autopsy specimens donated by patients who had suffered from a CNS malignancy. The researchers report a 10-fold decrease in neurogenesis in the brains of three patients with medulloblastoma who underwent cranial radiation, compared to controls. They also found a 100-fold decrease in neurogenesis in the brain of an infant patient who underwent radiation for leukaemia that spread to the CNS, compared to a control. The patients also exhibited an inflammatory response similar to that observed in the animal studies.The researchers hope further research will lead to a clinical trial of anti-inflammatory drugs for patients who undergo cranial radiation for brain tumours to lessen or eliminate the negative effects on neurogenesis, therefore improving or protecting memory function.The Hagerty Foundation funded this research.(Source: Annals of Neurology : Brigham and Women’s Hospital : November 2007)