Research Papers: Autophagy and Cell Death:

Lithium protects hippocampal progenitors, cognitive performance and hypothalamus–pituitary function after irradiation to the juvenile rat brain

Kai Zhou, Cuicui Xie, Malin Wickström, Amalia M. Dolga, Yaodong Zhang, Tao Li, Yiran Xu, Carsten Culmsee, Per Kogner, Changlian Zhu and Klas Blomgren _

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Oncotarget. 2017; 8:34111-34127. https://doi.org/10.18632/oncotarget.16292

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Kai Zhou1,2, Cuicui Xie1,3, Malin Wickström2, Amalia M. Dolga4,5, Yaodong Zhang1,6, Tao Li1,3,6, Yiran Xu1,3, Carsten Culmsee4, Per Kogner2,7, Changlian Zhu1,3,* and Klas Blomgren2,7,*

1 Centre for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden

2 Karolinska Institutet, Department of Women’s and Children’s Health, Stockholm, Sweden

3 Henan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China

4 Institute of Pharmacology and Clinical Pharmacy, University of Marburg, Marburg, Germany

5 Department of Molecular Pharmacology, University of Groningen, Groningen Research Institute of Pharmacy, Groningen, The Netherlands

6 Department of Paediatrics, Zhengzhou Children’s Hospital, Zhengzhou, China

7 Department of Paediatric Oncology, Karolinska University Hospital, Stockholm, Sweden

* These authors have equally contributed to this work

Correspondence to:

Klas Blomgren, email:

Changlian Zhu, email:

Keywords: brain tumour; cell death; late effects; neuroinflammation; radiotherapy

Received: September 07, 2016 Accepted: March 01, 2017 Published: March 16, 2017


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.

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