Pathological Mechanisms of Irradiation-Induced Neurological Deficits in the Developing Brain

Cranial irradiation or radiotherapy (CRT) is one of the essential therapeutic modalities for central nervous system (CNS) tumors, and its efficacy is well known. Nevertheless, CRT is also associated with brain damages such as focal cerebral necrosis, neuroinflammation, cerebral microvascular anomalies, neurocognitive dysfunction, and hormone deficiencies in children. Children's brains are much more sensitive to CRT compared to the adult's brains. Thus, children's brains are also more likely to develop long-term CRT complication, which severely lessens their long-term quality of life after treatment. CRT to the juvenile rat led to a retardation of growth of the cerebellum; both the gray and white matter and neurogenic regions like the subventricular zone and the dentate gyrus in the hippocampus were predominantly vulnerable to CRT. Also, CRT-induced cognitive changes typically manifested as deficits in hippocampal-related functions of learning as well as memory, such as spatial information processing. Fractionated CRT-stimulated cognitive decline and hormone deficiencies were precisely associated with augmented neuronal cell death, blockade of neurogenesis, and stimulation of astrocytes and microglia. Thus, the aim of this review is to highlight the pathological mechanism of CRT-induced neurological deficits in the developing brain.