Naringenin attenuates endoplasmic reticulum stress, reduces apoptosis, and improves functional recovery in experimental traumatic brain injury.

Traumatic brain injury (TBI) is a significant cause of disability and death worldwide. Accumulating evidence suggests that endoplasmic reticulum (ER) stress would be an important component in the pathogenesis of TBI. Although the neuroprotective effects of naringenin, a natural flavonoid isolated from citrus plants, have been confirmed in several neurological diseases, its mechanism of action in TBI needs further investigation. In ICR mice, we found that TBI induced elevated expression of ER stress marker proteins, including 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) in the perilesional cortex, which peaked at 7 days and 3 days after TBI, respectively. The induction of ER stress-related proteins partly coincided with ER architectural changes at 3 days post-TBI, indicating ER stress activation in our TBI model. Our results also revealed that continuous naringenin administration ameliorated neurological dysfunction, cerebral edema, plasmalemma permeability, and neuron cell loss at day 3 after TBI. Further, Naringenin suppressed TBI-induced activation of the ER stress pathway (p-eIF2α, ATF4, and CHOP), oxidative stress and apoptosis on day 3 after TBI. In summary, our data suggest that naringenin could ameliorate TBI-induced secondary brain injury by pleiotropic effects, including ER stress attenuation.

Correlation Between Vascular Geometry Changes and Long-Term Outcomes After Enterprise Stent Deployment for Intracranial Aneurysms Located on Small Arteries.

BACKGROUND: Enterprise stents are widely used for intracranial aneurysms located on small arteries (<2.5 mm in diameter) and change the geometry of parent arteries. The purpose of this study was to investigate the correlation between vascular geometry changes and long-term outcomes. METHODS: Between May 2013 and 2018, 1065 consecutive intracranial aneurysms were treated with Enterprise stents at our institution. After inclusion and exclusion criteria were applied, 377 aneurysms with >6 months of digital subtraction angiography follow-up were evaluated. The cohort comprised 101 aneurysms located on small parent arteries. After stent-assisted coiling, the vascular geometry parameters of small parent arteries were compared to explore their correlation with procedural complications, delayed stent migration, and recanalization. RESULTS: The rate of delayed aneurysm occlusion in patients with initial efferent artery diameter (De) <2.5 mm was significantly higher than in patients with De >2.5 mm (62.2% vs. 40.2%; P = 0.032). At follow-up, vascular geometry parameters significantly increased (P < 0.001). In multivariate analyses, larger aneurysms and initial parent artery angle (α) <90° were independent predictors of procedural complications and discrepancy in vessel size (ΔD) >0.5 mm was an independent predictor of delayed stent migration. Larger aneurysms and follow-up angle change (ΔAngle) <30° were independent predictors for recanalization of aneurysms located on small arteries. CONCLUSIONS: Enterprise stent-assisted coiling of intracranial aneurysms located on small arteries is safe and effective. Our study found that Enterprise deployment in small arteries had a low procedural complication rate and high stent tolerance. Vascular geometry changes play an important role in aneurysm recanalization.

Dihydroartemisinin initiates ferroptosis in glioblastoma through GPX4 inhibition.

It has been demonstrated from previous studies about the killing effect of dihydroartemisinin (DHA) on glioblastoma, which involves multiple aspects: cytotoxicity, cell cycle arrest and invasion inhibition. DHA has the advantages of low cytotoxicity to normal cells, selective killing effect and low drug resistance, making it one of the popular anti-tumor research directions. Ferroptosis is a newly discovered form of cell death characterized by iron dependence and lipid reactive oxygen species (ROS) accumulation. In the present study, we found differences in the expression of transferrin receptors in normal human astrocytes (NHA) and glioblastoma cells (U87 and A172), which may be one of the mechanisms of DHA selective killing effect. Through the determination of ferroptosis-related protein expression, we found that the significant decrease of GPX4, accompanied by the constant expression of xCT and ACSL4, suggesting GPX4 was a pivotal target for DHA-activated ferroptosis in glioblastoma. Total and lipid ROS levels were increased and all these results could be reversed by the ferroptosis inhibitor, ferrostatin-1. These findings demonstrated ferroptosis would be a critical component of cell death caused by DHA and GPX4 was the main target. All these results provide a novel treatment direction to glioblastoma. The association between ferroptosis and polyamines is also discussed, which will provide new research directions for ferroptosis caused by DHA in glioblastoma.