Iron homeostasis disturbance has been implicated in Alzheimer’s disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of ferroptosis in the pathogenesis of AD remains elusive. Here, we report that ferroportin1 (Fpn), the only identified mammalian nonheme iron exporter, was downregulated in the brains of APPswe/PS1dE9 mice as an Alzheimer’s mouse model and Alzheimer’s patients. Genetic deletion of Fpn in principal neurons of the neocortex and hippocampus by breeding Fpnfl/fl mice with NEX-Cre mice led to AD-like hippocampal atrophy and memory deficits. Interestingly, the canonical morphological and molecular characteristics of ferroptosis were observed in both Fpnfl/fl/NEXcre and AD mice. Gene set enrichment analysis (GSEA) of ferroptosis-related RNA-seq data showed that the differentially expressed genes were highly enriched in gene sets associated with AD. Furthermore, administration of specific inhibitors of ferroptosis effectively reduced the neuronal death and memory impairments induced by Aβ aggregation in vitro and in vivo. In addition, restoring Fpn ameliorated ferroptosis and memory impairment in APPswe/PS1dE9 mice. Our study demonstrates the critical role of Fpn and ferroptosis in the progression of AD, thus provides promising therapeutic approaches for this disease.

Objective Chronic subdural hematoma (CSDH) is a common neurosurgical condition with an increasing incidence and favorable prognosis. Surgery is the standard treatment for CSDH, and bur hole evacuation is the most widely employed technique. However, if mixed computed tomography (CT) density is found, burr hole hematoma evacuation is prone to recurrence. Endoscopic examination of the hematoma cavity provides a novel strategy. Here, we present a modification of burr hole evacuation by using neuroendoscopy through a novel small trapezoid bone flap and assess the advantages and risks of the procedure. Methods Twenty-five patients diagnosed with CSDH of mixed CT density were included in this study. Radiographic, epidemiologic, and clinical data were collected and analyzed. In all procedures the burr hole was replaced by a small trapezoidal cross-sectional bone flap, ∼2 cm in diameter. Neuroendoscopy was employed after the subdural cavity was cleaned and drained. The CSDH cavity was inspected thoroughly. If a blood clot, septa, stretching of cortical vessels, or intraluminal trabecular structures with active bleeding were found, the surgeon aspirated the region with a syringe pipe and/or used bipolar electrocoagulation. Results All 25 patients who received 26 neuroendoscopy-assisted operations achieved favorable clinical outcomes. The recurrence rate was 4%. The average operation time was slightly increased compared with the traditional burr hole evacuation due to the use of the neuroendoscope and eventual subsequent treatment. Conclusion Neuroendoscopy provides excellent illumination and vision when a small bone flap is employed. The main advantages of this technique include the precise treatment of structures which are related with progression and recurrence of CSDH, and the minimally invasive nature of the procedure.