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Lithium protects hippocampal progenitors, cognitive performance and hypothalamus-pituitary function after irradiation
Kai Zhou1,2, Cuicui Xie1,3, Malin Wickström2
1Centre for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Insights
Lithium treatment prevented cognitive decline, memory loss, and behavioral issues in juvenile rats after cranial radiation. This study highlights lithium
Area of Science:
- Neuroscience
- Pediatric Oncology
- Pharmacology
Background:
- Cranial radiotherapy in children often leads to cognitive dysfunction.
- Current preventive strategies for radiation-induced cognitive impairment are ineffective.
Purpose of the Study:
- To investigate the neuroprotective effects of lithium against cranial radiotherapy-induced brain injury in juvenile rats.
- To assess lithium's impact on neurogenesis, astrogenesis, and behavioral outcomes post-irradiation.
Main Methods:
- Administered lithium to juvenile rats before cranial irradiation.
- Assessed progenitor cell death, neurogenesis, and astrogenesis in the hippocampus.
- Evaluated memory, motor activity, anxiety-like behaviors, and pituitary function.
Main Results:
- Lithium reduced irradiation-induced progenitor cell death in the hippocampus.
- Lithium normalized neurogenesis, astrogenesis, and reversed memory deficits, hyperactivity, and anxiety.
- Lithium prevented late-onset hypopituitarism without affecting tumor cell viability in vitro.
Conclusions:
- Lithium demonstrates significant neuroprotective potential against cranial radiotherapy-induced brain injury in a juvenile rat model.
- Lithium may offer a safe and effective strategy for preventing both short- and long-term neurological and endocrine damage in pediatric patients undergoing radiation therapy.
- Further research is warranted to translate these findings into clinical applications for pediatric cancer survivors.
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.