Reduction of acute radiation-induced brain injury in rats by anlotinib

Abstract

Objectives Radiation therapy in the treatment of brain tumors also leads to the occurrence of radiation brain injury (RBI). Anlotinib is a small-molecule inhibitor of multi-receptor tyrosine kinase with high selectivity for vascular endothelial growth factor receptor-2. In this study, we constructed a rat model of RBI and investigated the effect of anlotinib on RBI and its mechanism of action through drug intervention during the acute phase of RBI. Methods Six-week-old male (Sprague–Dawley) rats were used to construct an animal model of RBI to evaluate the protective effect of anlotinib on acute RBI by histopathological staining, brain edema determination, blood–brain barrier integrity evaluation and quick real time-polymerase chain reaction , ELISA detection of inflammation-related indexes, and western-blot detection of related gene protein expression. Results Anlotinib reduced the degree of edema in the hippocampal region of rats, improved the pathological morphology of neural cells and vascular endothelial cells, and decreased blood–brain barrier permeability. Anlotinib reduced glial fibrillary acidic protein protein expression in the hippocampal region of rat brain tissue and inhibited astrocyte activation. It inhibited the release of inflammatory factors (interleukin [IL]-6, IL-8 and vascular endothelial growth factor) and down-regulated the expression of janus kinase-2/signal transducer and activator of transcription-3 (JAK2/STAT3) signaling pathway-related proteins. Conclusion This study found that anlotinib has a protective effect against RBI in rats and anlotinib may be a new candidate for the treatment of RBI.