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

Abstract

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 downregulating the activation of astrocytes, improving brain hypoxia, and alleviating cerebral edema.

Anlotinib Combined with Cranial Radiotherapy for Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Retrospectively, Control Study

“…8 In 2020 and 2021, oncologists suggested that anlotinib has intracranial activity and can control intracranial tumors. 12,20,21 The ALTER0303 study also showed that anlotinib can prolong PFS in lung cancer patients with BM. 12 Anlotinib normalizes the blood vessels in a metastatic tumor, adjusts the internal microenvironment of the tumor, restores the normal permeability of blood vessels, and acts synergistically with CRT to enhance radiosensitivity and reduce brain edema.…”

Nattokinase attenuates bisphenol A or gamma irradiation-mediated hepatic and neural toxicity by activation of Nrf2 and suppression of inflammatory mediators in rats

“…Moreover, radiation triggers neuroinflammation and significantly increased the brain levels of the pro-inflammatory mediators IL-1β, IL-6, and NF-κB (Lee et al 2010 ; Yang et al 2017 ). Besides, the astrocytes proliferate and exhibit hypertrophic nuclei/cell bodies with an apparent elevation in the GFAP expression upon radiation injury (Greene-Schloesser et al 2012 ; Gao et al 2021 ).…”

Mitigation of Acute Radiation-Induced Brain Injury by Anlotinib: A Meaningful Study

“…Although, anlotinib failed to inhibit the development of demyelination, anlotinib treatment significantly attenuated the adverse effects of acute RBI in a dose-dependent manner by downregulating astrocyte activation, ameliorating cerebral hypoxia, and alleviating cerebral edema [14]. [14] study elucidated the palliative effect of anlotinib on acute RBI at the molecular level, which clearly…”

“…Previously, GAO et al 's animal experiments on the mitigation of RBI by anlotinib were of great interest [14]. The authors evaluated changes in demyelination, glial cell activation, hypoxia, and microvascular permeability after anlotinib treatment by establishing a mouse model of RBI.…”