Reduction of lactoferrin aggravates neuronal ferroptosis after intracerebral hemorrhagic stroke in hyperglycemic mice

Abstract

Diabetic hyperglycemia aggravates the prognosis of intracerebral hemorrhagic stroke (ICH) in the clinic. In addition to hematoma expansion and increased inflammation, how diabetic hyperglycemia affects the outcomes of ICH is still unclear. We found that streptozotocin-induced diabetic hyperglycemia not only increased neutrophil infiltration, but also changed the gene expression profile of neutrophils, including lactoferrin (Ltf) encoding gene Ltf . Peroxisome proliferator-activated receptor γ (PPARγ) transcribed Ltf and the lack of neutrophilic Ltf transcription and secretion exacerbated neuronal ferroptosis by accumulating intraneuronal iron. Furthermore, the administration of recombinant Ltf protected against neuronal ferroptosis and improved neurobehavior in hyperglycemic ICH mice, and vice versa . These results indicate that supplementing Ltf or inhibiting neuronal ferroptosis are promising potential strategies to improve the acute outcomes of diabetic ICH in the clinic.

Inhibition of the LRRC8A channel promotes microglia/macrophage phagocytosis and improves outcomes after intracerebral hemorrhagic stroke

“…330231) and used for quantitative PCR in the ABI 7500 Fast Block system (Applied Biosystems, USA). 76 The data were uploaded for analysis to the Qiagen website ( http://www.qiagen.com/geneglobe ). The data were calculated as fold change/regulation using the ΔΔCT method, in which delta CT is calculated between gene of interest and an average of reference genes, followed by ΔΔCT calculations [ΔCT (Test Group) − ΔCT (Control Group)].…”

The Development of Drug Delivery Systems for Efficient Intracranial Hemorrhage Therapy

“…Activating the neutrophil PPAR‐ γ signaling pathway to up‐regulate the expression of Ltf may be beneficial to the treatment of ICH. [ 51 ] In addition, studies have shown that IL‐27 can also regulate the expression of Ltf in neutrophils. Microglia are rapidly activated and secrete a large amount of IL‐27 after ICH.…”

Ferroptosis and Its Role in Chronic Diseases

“…Tau-mediated iron export inhibits ferroptosis after ischemic stroke [131]. Supplementing lactoferrin reduces the ferroptosis of nerve cells after diabetic ICH [132], while crocin reduces ICH-induced neuronal ferroptosis by increasing Nrf2 expression and nuclear translocation [133]. Dauricine represses nerve cell ferroptosis and brain injury after ICH by up-regulating GPX4 expression [134], while pyridoxal isonicotinoyl hydrazone, a lipophilic iron-chelating agent, alleviates hemorrhage stroke by decreasing ferroptosis and inflammation [135].…”