Interplay Between Key Molecular Signaling Pathways and Immune Players Following Brain Irradiation

Irradiation (IRT) has been used extensively for the diagnosis and treatment of primary as well as metastatic brain tumors. Although the susceptibility of the radiation-induced brain injury or damage (RIBI) is partially associated with the sensitivity of particular cell types, pathways of injury in other types of brain disease or damage implicate the significance of the interaction between cell compartments. IRT-induced double-strand breaks (DSBs) are the utmost detrimental kind of DNA damage, which result in cell death as well as sustainable chromosomal reconfigurations following IRT exposure to the brain. It is worth noting that IRT-induced DSBs, and stimulation of interplay of key signaling pathways such as mitogen-activated protein kinases (MAPK), JAK/STAT, phosphoinositide-3-kinase/protein kinase B/AKT (PI3K-PKB/AKT), protein 53 (p53), mammalian target of rapamycin (mTOR), NF-kB, transforming growth factor beta (TGF-β), tumor necrosis factor (TNF), as well as reactive oxygen species (ROS) to either trigger radiosensitization or radioresistance as well as RIBI mechanisms. Also, IRT is capable of influencing fundamental immune players like cluster of differentiation markers, the complement cascade, T cells, B cells, interleukins, as well as chemotactic cytokines. Thus, the aim of this review is to explicate the key molecular signaling and immune mechanisms associated with IRT-induced neurological deficits following brain IRT.