Cognitive dysfunction induced by cranial radiotherapy: mechanisms and therapeutic methods

Cranial radiotherapy can damage normal brain tissues, inducing cognitive dysfunction in patients. Radiotherapy-induced cognitive dysfunction is associated with hippocampal injury, white matter damage and microvascular injury. In this study, the mechanisms of cognitive dysfunction induced by cranial radiotherapy and combined chemoradiotherapy are reviewed, and the advances in therapeutic methods for radiotherapy-induced brain injury are summarized. The mechanisms of radiotherapy-induced brain injury include a decline of neurogenesis, impairment of neurons and glial cells, vascular injury, oxidative stress and DNA damage, cell death, and inflammatory response. Disruption of the bloodbrain barrier (BBB) increases the exposure of the brain to chemotherapeutic agents, thus exacerbating radiotherapy-induced brain damage. The current methods used to prevent radiotherapy-induced brain injury mainly include precision radiotherapy, stem cell transplantation, and treatment with neuroprotective drugs. The combined application of precision radiotherapy and neuroprotective drugs, including antioxidants, anti-inflammatory agents and other drugs, might exert better neuroprotective effects. To resolve the issues of neuroprotective drugs, such as difficulty in crossing the BBB, nanoenzymes and drug delivery nano-systems could be applied in the future.