Ferroptosis is a regulated cell death that characterizes the lethal lipid peroxidation and iron overload, which may contribute to early brain injury (EBI) pathogenesis after subarachnoid hemorrhage (SAH). Although Sirtuin 1 (SIRT1), a class III histone deacetylase, has been proved to have endogenous neuroprotective effects on the EBI following SAH, the role of SIRT1 in ferroptosis has not been studied. Hence, we designed the current study to determine the role of ferroptosis in the EBI and explore the correlation between SIRT1 and ferroptosis after SAH. The pathways of ferroptosis were examined after experimental SAH in vivo (prechiasmatic cistern injection mouse model) and in HT-22 cells stimulated by oxyhemoglobin (oxyHb) in vitro. Then, ferrostatin-1 (Fer-1) was used further to determine the role of ferroptosis in EBI. Finally, we explored the correlation between SIRT1 and ferroptosis via regulating the expression of SIRT1 by resveratrol (RSV) and selisistat (SEL). Our results showed that ferroptosis was involved in the pathogenesis of EBI after SAH through multiple pathways, including acyl-CoA synthetase long-chain family member 4 (ACSL4) activation, iron metabolism disturbance, and the downregulation of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1). Inhibition of ferroptosis by Fer-1 significantly alleviated oxidative stress-mediated brain injury. SIRT1 activation could suppress SAH-induced ferroptosis by upregulating the expression of GPX4 and FSP1. Therefore, ferroptosis could be a potential therapeutic target for SAH, and SIRT1 activation is a promising method to inhibit ferroptosis.

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Indoxacarb is a recently introduced insecticide whose mode of action is blockage of voltage-gated sodium channels. There are limited data on human ingestion. A case of 68-year-old healthy male who presented with general cyanosis because of methemoglobinemia following the ingestion of indoxacarb is presented. After receiving a methylene blue injection, the patient recovered without sequelae.

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BackgroundSystemic responses, especially inflammatory responses, after aneurysmal subarachnoid hemorrhage (SAH) are closely related to clinical outcomes. Our study aimed to explore the correlation between the systemic responses in the acute stage and the mid-term outcomes of severe SAH patients (Hunt-Hess grade III-V).Materials and methodsSevere SAH patients admitted to Jinling Hospital from January 2015 to December 2019 were retrospectively analyzed in the study. The univariate and multivariate logistic regression analyses were used to explore the risk factors of 6-month clinical outcomes in severe SAH patients. A predictive model was established based on those risk factors and was visualized by a nomogram. Then, the predictive nomogram model was validated in another severe SAH patient cohort from January 2020 to January 2022.ResultsA total of 194 patients were enrolled in this study. 123 (63.4%, 123 of 194) patients achieved good clinical outcomes at the 6-month follow-up. Univariate and multivariate logistic regression analysis revealed that age, Hunt-Hess grade, neutrophil-to-lymphocyte ratio (NLR), and complications not related to operations were independent risk factors for unfavorable outcomes at 6-month follow-up. The areas under the curve (AUC) analysis showed that the predictive model based on the above four variables was significantly better than the Hunt-Hess grade (0.812 vs. 0.685, P = 0.013). In the validation cohort with 44 severe SAH patients from three different clinical centers, the AUC of the prognostic nomogram model was 0.893.ConclusionThe predictive nomogram model could be a reliable predictive tool for the outcome of severe SAH patients. Systemic inflammatory responses after SAH and complications not related to operations, especially hydrocephalus, delayed cerebral ischemia, and pneumonia, might be the important risk factors that lead to poor outcomes in severe SAH patients.

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