| 1. |
- Han, W., et al.
(författare)
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Cranial irradiation induces transient microglia accumulation, followed by long-lasting inflammation and loss of microglia
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:50, s. 82305-82323
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Tidskriftsartikel (refereegranskat)abstract
- The relative contribution of resident microglia and peripheral monocyte-derived macrophages in neuroinflammation after cranial irradiation is not known. A single dose of 8 Gy was administered to postnatal day 10 (juvenile) or 90 (adult) CX3CR1(GFP/+) CCR2(RFP/+) mouse brains. Microglia accumulated in the subgranular zone of the hippocampal granule cell layer, where progenitor cell death was prominent. The peak was earlier (6 h vs. 24 h) but less pronounced in adult brains. The increase in juvenile, but not adult, brains was partly attributed to proliferation. Microglia numbers then decreased over time to 39% (juvenile) and 58% (adult) of controls 30 days after irradiation, largely as a result of cell death. CD68 was expressed in 90% of amoeboid microglia in juvenile hippocampi but only in 9% of adult ones. Isolated hippocampal microglia revealed reduced CD206 and increased IL1-beta expression after irradiation, more pronounced in juvenile brains. CCL2 and IL-1 beta increased after irradiation, more in juvenile hippocampi, and remained elevated at all time points. In summary, microglia activation after irradiation was more pronounced, protracted and pro-inflammatory by nature in juvenile than in adult hippocampi. Common to both ages was long-lasting inflammation and the absence of monocyte-derived macrophages.
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| 2. |
- Zhou, Kai, et al.
(författare)
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Lithium protects hippocampal progenitors, cognitive performance and hypothalamus-pituitary function after irradiation to the juvenile rat brain
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:21, s. 34111-34127
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Tidskriftsartikel (refereegranskat)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.
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