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Objective: Animal models of brain and spinal cord metastases of non-small cell lung cancer were established through the intracranial injection of PC-9 Luc cells with a brain stereotaxic device. This method provides a reliable modeling method for studying brain and spinal cord metastases of non-small cell lung cancer. Methods: PC-9 Luc cells at logarithmic growth stage were injected into the skulls of 5-week-old BALB/c nude mice at different cell volumes (30 × 104, 80 × 104) and different locations (using anterior fontanel as a location point, 1 mm from the coronal suture, and 1.5 mm from the sagittal suture on the right upper and right lower side of the skull). After 1 week of cell inoculation, fluorescence signals of tumor cells in the brain and spinal were detected using the IVIS Xenogen Imaging system. After 4 weeks, brain and spinal tissues from the nude mice were harvested. Following paraffin-embedded sectioning, HE staining was performed on the tissues. Results: The fluorescence signals revealed that both brain and spinal cord metastasis occurred in the mice where the cells were injected at the lower right side of the skull. There was only brain metastasis in the nude mice injected with 30 × 104 cells at the upper right side of the skull. Both brain and spinal cord metastasis occurred in the nude mice injected with 80 × 104 cells. The HE staining revealed that both brain and spinal cord metastasis occurred in the mice injected with different amounts of PC-9 Luc cells, consistent with the results detected using the IVIS Xenogen Imaging system, thereby demonstrating the reliability of detecting fluorescent signals in vivo to determine tumor growth. Conclusion: It is a reliable method to establish the animal model of brain and spinal cord metastases of non-small cell lung cancer by injecting different quantities of cells from different positions with a brain stereotaxic device. The IVIS Xenogen Imaging system has high reliability in detecting the fluorescence signals of brain and spinal cord metastatic tumors.

Roughly one third of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-sensitive mutated (EGFRm) tumors experience disease progression through central nervous system (CNS) metastases during treatment. Although EGFR-TKIs have been reported to be favored in some patients with EGFRm NSCLC CNS metastases, novel EGFR-TKIs with proven efficacy in CNS pathologies are clinically needed.To investigate whether almonertinib, a novel third-generation EGFR-TKI for NSCLC, can cross the blood-brain barrier (BBB) and deliver treatment for EGFR-mutant NSCLC brain metastases and spinal cord metastases, we constructed NSCLC brain metastasis and spinal cord metastasis models in vivo to observe the anti-tumor effects of almonertinib. Using ABCB1-MDCK and BCRP-MDCK monolayer cells as the in vitro study model, the effects of transport time and drug concentration on the apparent permeability coefficient of almonertinib and its active metabolite, HAS-719, were investigated. The results of this study show that almonertinib can significantly inhibit PC9 brain and spinal cord metastases. Pharmacokinetic studies in mice revealed that almonertinib has good BBB penetration ability, whereas the metabolite HAS-719 does not easily penetrate the BBB. Early clinical evidence of almonertinib activity in patients with EGFRm-advanced NSCLC and brain metastases has also been reported. In conclusion, almonertinib easily penetrates the BBB and inhibits advanced NSCLC brain and spinal cord metastases.

Cerebral ischemia reperfusion ( CIR ) has become the leading cause of death and disability. Baicalein is a natural bioactive ingredient extracted from Scutellaria baicalensis Georgi and has neuroprotective activity. In our work, baicalein was found to reduce neurological deficits, brain water content, infarct area, and neuronal death of rats induced by middle cerebral artery occlusion/reperfusion. In vitro, oxygen--glucose deprivation/reperfusion induced inordinate ROS production and apoptosis that could be reversed by baicalein. Our study revealed for the first time that baicalein has the potential to bind and inhibit the activity of calpain 1, thereby inhibiting AIF nuclear translocation. These findings demonstrated that baicalein protected against CIR injury via inhibiting AIF nuclear translocation by inhibiting calpain 1 activity. [ABSTRACT FROM AUTHOR]