Subarachnoid hemorrhage (SAH) has a high mortality rate and causes long-term disability in many patients, often associated with cognitive impairment. However, the pathogenesis of delayed brain dysfunction after SAH is not fully understood. A growing body of evidence suggests that neuroinflammation and oxidative stress play a negative role in neurofunctional deficits. Red blood cells and hemoglobin, immune cells, proinflammatory cytokines, and peroxidases are directly or indirectly involved in the regulation of neuroinflammation and oxidative stress in the central nervous system after SAH. This review explores the role of various cellular and acellular components in secondary inflammation and oxidative stress after SAH, and aims to provide new ideas for clinical treatment to improve the prognosis of SAH.

Numerous in vitro studies have indicated that acetaminophen is activated by mouse hepatic microsomal cytochrome P450 to form N-acetylbenzoquinone imine. This in turn covalently binds through a Michael addition to protein sulfhydryl and amino groups. Although acetaminophen adducts of several cytosolic proteins have been purified after its administration in vivo, no adducts of specific microsomal proteins have been reported. We find that, after the in vitro incubation of mouse hepatic microsomes with [ring-14C] acetaminophen in the presence of an NADPH generating system, 95% of the bound radioactivity was associated with adducts to three intraluminal microsomal proteins: calreticulin and the two forms of thiol:protein disulfide oxidoreductase, Q2 and Q5. The acetaminophen bound to 0.35, 1.32, and 0.25 mol/mol of the three proteins, respectively. Sequencing of the 14C-labeled tryptic peptides indicated that the acetaminophen bound to lysine 103 of Q2, lysines 202, 209 or 210 and 354 of Q5 and lysines 233 or 239 of calreticulin. No adducts of cysteine residues were observed. Our data might suggest that acetaminophen hepatotoxicity results from the formation of the reactive metabolite within the endoplasmic reticulum. This then binds to these essential proteins and blocks the posttranslational modification of secretory and membrane proteins. This inhibition could then lead to cellular injury and death.

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Background: Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as World Federation of Neurosurgical Societies (WFNS) grades IV–V have high rates of disability and mortality. The objective of this study was to accurately prognosticate the outcomes of patients with poor-grade aSAH by developing a new scoring model.Methods: A total of 147 poor-grade aSAH patients in our center were enrolled. Risk variables identified by multivariate logistic regression analysis were used to devise a scoring model (total score, 0–9 points). The scores were estimated on the basis of β coefficients. A cohort of 68 patients from another institute was used to validate the model.Results: Multivariate logistic regression analysis revealed that modified Fisher grade >2 [odds ratio [OR], 2.972; P = 0.034], age ≥65 years (OR, 3.534; P = 0.006), conservative treatment (OR, 5.078; P = 0.019), WFNS grade V (OR, 2.638; P = 0.029), delayed cerebral ischemia (OR, 3.170; P = 0.016), shunt-dependent hydrocephalus (OR, 3.202; P = 0.032), and cerebral herniation (OR, 7.337; P < 0.001) were significant predictors for poor prognosis [modified Rankin Scale [mRS] ≥3]. A scoring system was constructed by the integration of these factors and divided the poor-grade aSAH patients into three categories: low risk (0–1 points), intermediate risk (2–3 points), and high risk (4–9 points), with predicted risks of poor prognosis of 11, 52, and 87%, respectively (P < 0.001). The area under the curve in the derivation cohort was 0.844 (95% CI, 0.778–0.909). The AUC in the validation cohort was 0.831 (95% CI, 0.732–0.929).Conclusions: The new scoring model can improve prognostication and help decision-making for subsequent complementary treatment in patients with aSAH.

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Background Whether IL-15 is involved in the development of steroid-induced osteonecrosis of the femoral head (ONFH) is investigated. Methods C57BL/6 J and l15−/−mice were injected with methylprednisolone to induce wide type osteonecrosis (WT ON) and IL-15 deficiency osteonecrosis (IL-15−/− ON). Hematoxylin-Eosin (H&E) staining and micro-computed tomography (micro-CT) scanning was used to detect the microstructure. The differentiation and formation of osteoclasts were determined with colony-forming unit-granulocyte macrophages (CFU-GM), colony-forming unit-macrophage/mononuclear (CFU-M) per tibia, and tartrate-resistant acid phosphatase (TRACP or TRAP) positive cells. Serum interleukin (IL)-15, osteocalcin, bone alkaline phosphatase (BAP), bone Gla protein (BGP), and TRACP were assayed with enzyme-linked immunosorbent assay (ELISA). The receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in the femoral heads were detected by Western blot. CD34 staining was performed to detect microvascular density. Results IL-15 secretion was increased in the femoral heads and the serum of steroid-induced ONFH mice. IL-15 deficiency may lead to up-regulated vessel remodeling, improved microstructure, and up-regulated serum osteocalcin, BAP, and BGP secretion. Both the expression of RANKL/RANK/OPG and osteoclast differentiation and formation can be down-regulated by IL-15 deficiency. Conclusion IL-15 deficiency alleviates steroid-induced ONFH by impact osteoclasts via RANKL-RANK-OPG system.