Abstract
Cranial radiotherapy in children typically causes delayed and progressive cognitive dysfunction and there is no effective preventive strategy for radiation-induced cognitive impairments. Here we show that lithium treatment reduced irradiation-induced progenitor cell death in the subgranular zone of the hippocampus, and subsequently ameliorated irradiation-reduced neurogenesis and astrogenesis in the juvenile rat brain. Irradiation-induced memory impairment, motor hyperactivity and anxiety-like behaviour were normalized by lithium treatment. Late-onset irradiation-induced hypopituitarism was prevented by lithium treatment. Additionally, lithium appeared relatively toxic to multiple cultured tumour cell lines, and did not improve viability of radiated DAOY cells in vitro. In summary, our findings demonstrate that lithium can be safely administered to prevent both short- and long-term injury to the juvenile brain caused by ionizing radiation.
Highlights
Brain tumours are the most frequent paediatric solid tumours and they represent the leading cause of mortality and morbidity by cancer in this age group [1]
To examine the sensitivity difference of human tumour cells to lithium treatment, 7 brain tumour cell lines were treated with lithium at different concentrations, and as a comparison a neural multipotent progenitor cell line was included in the analysis
We further examined the combined effects of lithium and irradiation on DAOY cells, a medulloblastoma cell line which is resistant to irradiation
Summary
Brain tumours are the most frequent paediatric solid tumours and they represent the leading cause of mortality and morbidity by cancer in this age group [1]. Current treatment protocols for malignant paediatric brain tumours, the most common of which is medulloblastoma, typically include surgery, irradiation, and chemotherapy, a lifesaving combination that contributes to long-term physical, endocrine, and neuropsychological impairments in survivors [2]. Radiotherapy often causes delayed and progressive cognitive impairments, such as deficits in memory, attention, and executive function [3, 4] with tremendous impact on the patients’ quality of life. Cognitive function is one of the most important measurements of brain tumour therapy outcomes in clinical trials, second only to survival [5]. Clinical studies suggest that radiation-induced damage to the hippocampus plays a significant role in cognitive deficits [6,7,8]. Systemic effects of cranial irradiation, especially radiation-induced endocrinopathies, influence mental and physical development [12]
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