Mitigation of acute radiation-induced brain injury in a mouse model using anlotinib

作者：Xiaohan Gao, Jing Zheng, Long Ma, Longbo Ma, Yujie Zhai, Fangfang Yang, Shengjie Wang, Qing-Shuai Fan, Jie Wen, Henglu Wang, Xiaohan Wu, Shaoshui Chen, Changmin Liu · 发表于：Annals of Palliative Medicine · 年份：2021 · DOI：10.21037/apm-20-2284 · 被引用次数：13 · 研究领域：Lung Cancer Research Studies、Brain Metastases and Treatment、Angiogenesis and VEGF in Cancer

BACKGROUND: With the development of radiological technologies, radiotherapy has been gradually widely used in the clinic to intracranial tumours and become standardised. However, the related central nervous system disorders are still the most obvious complications after radiotherapy. This study aims to quantify the effectiveness of anlotinib, a small molecule inhibitor of multiple receptor tyrosine kinases, in mitigating acute phase of radiation-induced brain injury (RBI) in a mouse model. METHODS: The onset and progression of RBI were investigated in vivo. All mice, (except for the sham group) were irradiated at a single-fraction of 20 Gy and treated with different doses of anlotinib (0, 0.2 and 0.8 mg/kg, respectively). The expression levels of glial fibrillary acidic protein (GFAP), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated vascular endothelial growth factor receptor-2 (p-VEGFR2) were assessed by western blot. Histological changes were identified by luxol fast blue (LFB) staining. RESULTS: The expression levels of GFAP, HIF-1α, and VEGF were downregulated following treatment with anlotinib. However, anlotinib failed to inhibit the development of demyelination. Cerebral edema [as measured by brain water content (BWC)] was also mitigated following treatment with anlotinib. CONCLUSIONS: In summary, treatment with anlotinib significantly mitigated the adverse effects of acute RBI in a dose-dependent manner by downregula...