Abstract
The brain undergoes ionizing radiation (IR) exposure in many clinical situations, particularly during radiotherapy for malignant brain tumors. Cranial radiation therapy is related with the hazard of long-term neurocognitive decline. The detrimental ionizing radiation effects on the brain closely correlate with age at treatment, and younger age associates with harsher deficiencies. Radiation has been shown to induce damage in several cell populations of the mouse brain. Indeed, brain exposure causes a dysfunction of the neurogenic niche due to alterations in the neuronal and supporting cell progenitor signaling environment, particularly in the hippocampus—a region of the brain critical to memory and cognition. Consequent deficiencies in rates of generation of new neurons, neural differentiation and apoptotic cell death, lead to neuronal deterioration and lasting repercussions on neurocognitive functions. Besides neural stem cells, mature neural cells and glial cells are recognized IR targets. We will review the current knowledge about radiation-induced damage in stem cells of the brain and discuss potential treatment interventions and therapy methods to prevent and mitigate radiation related cognitive decline.
Highlights
Benefit to patients from medical uses of ionizing radiation (IR) has been established beyond doubt
The permanent cognitive decline that is often associated to brain radiotherapy is likely multifactorial in its origins; improved understanding of the mechanisms of IR-induced cognitive decline will be needed in order to select candidate therapeutics
Subsequent interesting work by the same group undertook manipulation of the redox balance in the hippocampus using a bigenic mouse model overexpressing EC-SOD (OE) in the granule cell layer, in an overall EC-SOD-deficient environment. They showed that OE and KO mice exhibit similar hippocampal-related functions following cranial irradiation; molecular examinations suggested that this may be governed by distinct mechanisms, with neurotrophic factors influencing IR
Summary
Benefit to patients from medical uses of ionizing radiation (IR) has been established beyond doubt. With cognitivemanifest decline numerous involves damage neural cell types, causing structuralworse and functional improvement of technologies (e.g., intensity modulated radiotherapy (IMRT), stereotactic radiosurgery, alterations in the brain blood vessels and in glial cell populations, reducing neurogenesis in the intracranial brachytherapy and limited size) normal tissue damage[9]. Neurocognitive deficits, including learning, memory, spatial processing, and dementia still brain radiation injury leads to a persistent alteration in the brain’s milieu, with inflammation playing persist [3].role. Of early treatments with potential cognitive to ameliorate or involves damage in CNS multiple neural cell be types, causing structural and therapy functional alterations in the prevent IR-induced damage would highly beneficial for cancer outcomes [9,12].
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