Whole brain radiation-induced cognitive impairment: Pathophysiological mechanisms and therapeutic targets

Abstract

Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major signifi cance in tumor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large fi eld or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional defi cits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a signifi cant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cellular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the identifi cation of novel therapeutic targets. Specifi cally, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-infl ammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defi ning a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy. © 2012 The Korean Society of Applied Pharmacology.