Radiation-induced brain injury: current concepts and therapeutic strategies targeting neuroinflammation

Abstract

Continued improvements in cancer therapies have increased the number of long-term cancer survivors. Radiation therapy remains one of the primary treatment modalities with about 60% of newly diagnosed cancer patients receiving radiation during the course of their disease. While radiation therapy has dramatically improved patient survival in a number of cancer types, the late effects remain a significant factor affecting the quality of life particularly in pediatric patients. Radiation-induced brain injury can result in cognitive dysfunction, including hippocampal-related learning and memory dysfunction that can escalate to dementia. In this article, we review the current understanding of the mechanisms behind radiation-induced brain injury focusing on the role of neuroinflammation and reduced hippocampal neurogenesis. Approaches to prevent or ameliorate treatment-induced side effects are also discussed along with remaining challenges in the field.

The Abscopal Effects of Cranial Irradiation Induce Testicular Damage in Mice

“…Notably, its incidence is increasing each year, and there is a trend towards a decreasing age at onset; thus, this disease seriously threatens human health. Cranial irradiation (C-irradiation) therapy is one of the major treatment modalities for primary and metastatic head and neck cancer ( Siegel et al, 2020 ; Turnquist et al, 2020 ). Hypofractionated radiation (single dose >2.5 Gy) is a promising new strategy for radiotherapy due to its higher treatment ratio, shorter total treatment time and lower cost than conventional radiotherapy (single dose=2.0Gy; Azoulay et al, 2017 ; Isfahanian et al, 2017 ; Rudat et al, 2017 ; Vischioni et al, 2019 ).…”

Alopecia and neurocognitive dysfunction in Glioblastoma multiforme patients- Prevention feasibillity by dosimetric analysis in conformal radiotherapy techniques

“…Radiation induced irreversible delayed brain injury is known to occur six months after radiation leading to white matter necrosis, vascular abnormalities, permanent demyelination, gliosis manifesting as neurocognitive sequelae. 10 With advancements in radiotherapy techniques and incorporation of newer targeted therapy in the management of GBM patients, the survivals are increasing. Therefore, a large proportion of the patients are likely to manifest this sequelae and the recognition of IMRT technique becomes a key consideration.…”

Can Rational Combination of Ultra-high Dose Rate FLASH Radiotherapy with Immunotherapy Provide a Novel Approach to Cancer Treatment?

“…Cognitive protection in juvenile and adult mice has been consistently reported in multiple publications using FLASH-RT for brain irradiation [11e13,32]. Radiation-induced brain injury is a complicated process that involves vascular abnormalities, loss of hippocampal neurogenesis, glial activation and neural progenitor cell death [51]. Among these neuropathological alterations, microglia and astrocyte activation plays a critical role in initiating the inflammatory cascade in irradiated brains [52].…”