Breaking barriers: Neurodegenerative repercussions of radiotherapy induced damage on the blood-brain and blood-tumor barrier

Exposure to radiation during the treatment of CNS tumors leads to detrimental damage of the blood brain barrier (BBB) in normal tissue. Effects are characterized by leakage of the vasculature which exposes the brain to a host of neurotoxic agents potentially leading to white matter necrosis, parenchymal calcification, and an increased chance of stroke. Vasculature of the blood tumor barrier (BTB) is irregular leading to poorly perfused and hypoxic tissue throughout the tumor that becomes resistant to radiation. While current clinical applications of cranial radiotherapy use dose fractionation to reduce normal tissue damage, these treatments still cause significant alterations to the cells that make up the neurovascular unit of the BBB and BTB. Damage to the vasculature manifests as reduction in tight junction proteins, alterations to membrane transporters, impaired cell signaling, apoptosis, and cellular senescence. While radiotherapy treatments are detrimental to normal tissue, adapting combined strategies with radiation targeted to damage the BTB could aid in drug delivery. Understanding differences between the BBB and the BTB may provide valuable insight allowing clinicians to improve treatment outcomes. Leveraging this information should allow advances in the development of therapeutic modalities that will protect the normal tissue while simultaneously improving CNS tumor treatments.