Transcriptomics and metabolomics reveal hypothalamic metabolic characteristics and key genes after subarachnoid hemorrhage in rats.

Subarachnoid hemorrhage (SAH) is a serious hemorrhagic event with high mortality and morbidity. Multiple injurious events produced by SAH can lead to a series of pathophysiologic processes in the hypothalamus that can severely impact patients' life. These pathophysiologic processes usually result in physiologic derangements and dysfunction of the brain and multiple organs. This dysfunction involved multiple dimensions of the genome and metabolome. In our study, we induced the SAH model in rats to obtain hypothalamic tissue and serum. The samples were subsequently analyzed by transcriptomics and metabolomics. Next, the functional enrichment analysis of the differentially expressed genes and metabolites were performed by GO and KEGG pathway analysis. Through transcriptomic analysis of hypothalamus samples, 263 up-regulated differential genes, and 207 down-regulated differential genes were identified in SAH groups compared to Sham groups. In the KEGG pathway analysis, a large number of differential genes were found to be enriched in IL-17 signaling pathway, PI3K-Akt signaling pathway, and bile secretion. Liquid chromatography-mass spectrometry metabolomics technology was conducted on the serum of SAH rats and identified 11 up-regulated and 26 down-regulated metabolites in positive ion model, and 1 up-regulated and 10 down-regulated metabolites in negative ion model. KEGG pathways analysis showed that differentially expressed metabolites were mainly enriched in pathways of bile secretion and primary bile acid biosynthesis. We systematically depicted the neuro- and metabolism-related biomolecular changes occurring in the hypothalamus after SAH by performing transcriptomics and metabolomics studies. These biomolecular changes may provide new insights into hypothalamus-induced metabolic changes and gene expression after SAH.

Scoring model to predict postoperative neurological deterioration in spinal schwannoma.

Background: Spinal schwannomas (SSs) are benign tumors affecting the nerve sheath, accounting for 25% of spinal nerve root tumors. Surgery represents the mainstay of treatment for SS patients. Following surgery, approximately 30% of patients experienced developed new or worsening neurological deterioration, which probably represented an inevitable complication of nerve sheath tumor surgery. The objective of this study was to identify the rates of new or worsening neurological deterioration in our center and accurately predict the neurological outcomes of patients with SS by developing a new scoring model. Methods: A total of 203 patients were retrospectively enrolled at our center. Risk factors associated with postoperative neurological deterioration were identified by multivariate logistic regression analysis. ß-coefficients for independent risk factors were used to define a numerical score to generate a scoring model. The validation cohort at our center was used to verify the accuracy and reliability of the scoring model. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the scoring model. Results: In this study, five measured variables were selected for the scoring model: duration of preoperative symptoms (1 point), radiating pain (2 points), tumor size (2 points), tumor site (1 point), and dumbbell tumor (1 point). The scoring model divided the spinal schwannoma patients into three categories: low risk (0-2 points), intermediate risk (3-5 points), and high risk (6-7 points), with predicted risks of neurological deterioration of 8.7%, 36%, and 87.5%, respectively. And the validation cohort confirmed the model with the predicted risks of 8.6%, 46.4%, and 66.6%, respectively. Conclusion: The new scoring model might intuitively and individually predict the risk of neurological deterioration and may aid individualized treatment decision-making for SS patients.

Elevated Serum CCL23 Levels at Admission Predict Delayed Cerebral Ischemia and Functional Outcome after Aneurysmal Subarachnoid Hemorrhage.

(1) Background: CC chemokine ligand 23 (CCL23) is a chemokine implicated in the inflammatory response following brain damage. The aim of this study is to identify the change in serum CCL23 levels within 24 h after aSAH and whether serum CCL23 levels are associated with initial clinical severity, delayed cerebral ischemia (DCI), and functional outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). (2) Methods: 102 patients with aSAH and 61 controls were included in this prospective observational study. All clinical data were collected prospectively, and their serum CCL23 levels were measured. Initial clinical severity was reflected by the Hunt-Hess score and mFisher score. Functional outcome was evaluated in terms of the Glasgow Outcome Scale (GOS) score at 6-month follow-up. (3) Results: Patients with aSAH had higher serum CCL23 levels than controls. The temporal profile of serum CCL23 levels and neutrophils count exhibited a sustained increase within 24 h after aSAH. Serum CCL23 levels were related to blood neutrophils count, blood CRP levels, and initial clinical severity. Serum CCL23 level was an independent predictor of DCI and 6-month poor outcome in aSAH patients. (4) Conclusions: Serum CCL23 levels emerged as an independent predictor for DCI and poor outcome in patients with aSAH.

Systemic immune responses after ischemic stroke: From the center to the periphery.

Ischemic stroke is a leading cause of disability and death. It imposes a heavy economic burden on individuals, families and society. The mortality rate of ischemic stroke has decreased with the help of thrombolytic drug therapy and intravascular intervention. However, the nerve damage caused by ischemia-reperfusion is long-lasting and followed by multiple organ dysfunction. In this process, the immune responses manifested by systemic inflammatory responses play an important role. It begins with neuroinflammation following ischemic stroke. The large number of inflammatory cells released after activation of immune cells in the lesion area, along with the deactivated neuroendocrine and autonomic nervous systems, link the center with the periphery. With the activation of systemic immunity and the emergence of immunosuppression, peripheral organs become the second "battlefield" of the immune response after ischemic stroke and gradually become dysfunctional and lead to an adverse prognosis. The purpose of this review was to describe the systemic immune responses after ischemic stroke. We hope to provide new ideas for future research and clinical treatments to improve patient outcomes and quality of life.

Serum CCL23 emerges as a biomarker for poor prognosis in patients with intracerebral hemorrhage.

BACKGROUND: CCL23 is involved in the inflammatory response and associated with the progression of brain injury. Herein, we assessed the relationship between serum CCL23 levels and inflammation, hematoma severity, and unfavorable outcome after intracerebral hemorrhage (ICH). METHODS: In this prospective observational study of 94 ICH patients and 47 controls, serum CCL23 levels were measured. Hemorrhage severity was reflected by the National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume. An unfavorable outcome was defined as a modified Rankin Scale > 2 at 6 months after ICH. Its association with clinical outcome was confirmed using the binary logistic regression analysis. Predictive efficiency was verified under receiver operating characteristic (ROC) curve. RESULTS: Significantly increased serum CCL23 levels were observed in ICH patients, as compared to controls. Serum CCL23 levels were highly related to NIHSS score, hematoma volume, ICH score, Glasgow coma scale score, serum C-reactive protein levels, blood leucocyte count, and neutrophil count. CCL23 ≥ 62.95 pg/ml served as an independent predictor of 6-month unfavorable outcome and death, and its validity was confirmed by ROC analysis. CONCLUSION: CCL23 may be implicated in the inflammatory response and serve as a potential marker for predicting the prognosis of patients with ICH.

Association between systemic inflammatory response syndrome and hematoma expansion in intracerebral hemorrhage.

BACKGROUND: Hematoma expansion (HE) is a relatively common complication after intracerebral hemorrhage. OBJECTIVES: To explore the association between systemic inflammatory response syndrome (SIRS) and HE in patients with intracerebral hemorrhage (ICH). MATERIAL AND METHODS: From June 2013 to October 2020, the sociodemographic data and clinical data of 780 ICH patients were collected. The logistic regression analysis with odd ratios (ORs) and 95% confidence intervals (95% CIs) was performed to analyze the risk factors for HE in patients with ICH. RESULTS: Hematoma expansion occurred in 151 (19.36%) patients with ICH. Significant differences were presented between SIRS and HE (OR = 2.549, 95% CI: [1.497; 4.342], p = 0.0006). After adjusting the covariates, a further analysis showed that the respiratory rate >20 beats/min (OR = 3.436, 95% CI: [1.981; 5.960], p < 0.0001), white blood cell (WBC) > 12×109/L or WBC ≤ 4×109/L (OR = 2.489, 95% CI: [1.494; 4.149], p = 0.0005) increased the risk for HE in ICH patients. Our study also found that the significant differences between HE and non-HE patients in proportion of patients with history of diabetes mellitus, basal ganglia hemorrhage, hypothalamus hemorrhage and fasting blood glucose (all p < 0.05) (OR = 2.076, 95% CI: [1.274; 3.381], p = 0.0034), basal ganglia hemorrhage (OR = 2.512, 95% CI: [1.496; 4.218], p = 0.0005), hypothalamus hemorrhage (OR = 2.121, 95% CI: [1.007; 4.466], p = 0.0479), high C-reactive protein (CRP) (OR = 1.013, 95% CI: [1.002; 1.024], p = 0.0184), and hyperglycemia (OR = 1.099, 95% CI: [1.026; 1.178], p = 0.0074) were associated with an increased risk of HE in ICH patients. CONCLUSIONS: The SIRS is closely associated with the risk of HE. Respiratory rate >20 beats/min and WBC count >12(109/L) or ≤4(109/L) increased the risk for HE in ICH patients. These findings can help to achieve the early prevention of HE and improve the prognosis of ICH patients.

Inflammation and Oxidative Stress: Potential Targets for Improving Prognosis After Subarachnoid Hemorrhage.

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.

Scoring Model to Predict Functional Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

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 ß 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.