Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

Abstract

Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors.

Inhibition of autophagy prevents irradiation-induced neural stem and progenitor cell death in the juvenile mouse brain

“…32 We found in this work that neuron-specific KO of Atg7 reduces neural stem and progenitor cell death and caspase-dependent apoptosis after irradiation both in the dentate gyrus and the cerebellum. The functional relationship between apoptosis and autophagy is complex, and these two processes might be triggered by common upstream signals.…”

Autopsy report of a late delayed radiation injury after a period of 45 years

“…Radiation therapy is used widely for the treatment of diffuse primary and metastatic brain tumors and is a common and effective therapy for many types of cancer. However, during treatment healthy brain tissue is also exposed to the radiation, and consequently many patients may experience neurological symptoms associated with damage to healthy tissues following radiotherapy Because of the potential for neurological problems, a number of excellent review articles have been published on radiation‐induced brain injury . Based on clinical symptoms, the complications of radiation therapy are divided into acute, early delayed, and late delayed injury .…”

“…However, during treatment healthy brain tissue is also exposed to the radiation, and consequently many patients may experience neurological symptoms associated with damage to healthy tissues following radiotherapy 2 Because of the potential for neurological problems, a number of excellent review articles have been published on radiation-induced brain injury. 3,4 Based on clinical symptoms, the complications of radiation therapy are divided into acute, early delayed, and late delayed injury. 5 As therapeutic techniques have improved and survival duration after irradiation has increased, there is a growing awareness of late delayed injuries including possible cerebrovascular and neurocognitive effects.…”

Neuroprotective effect of quercetin against radiation‐induced endoplasmic reticulum stress in neurons

“…IR is said to inhibit neurogenesis and also induces apoptosis in rat neural stem cells through the activation of the JNK pathway . Studies advocate that IR upregulates reactive oxygen species, oxidative stress, and apoptosis in the hippocampus, which causes the loss of neuronal progenitor cells, which in turn leads to the inhibition of neurogenesis . ER stress has also been shown to play a major role in the axonal injury .…”