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.

Predicting postacute phase anaemia after aneurysmal subarachnoid haemorrhage: nomogram development and validation.

BACKGROUND: Anaemia is a severe and common complication in patients with aneurysmal subarachnoid haemorrhage (aSAH). Early intervention for at-risk patients before anaemia occurs is indicated as potentially beneficial, but no validated method synthesises patients' complicated clinical features into an instrument. The purpose of the current study was to develop and externally validate a nomogram that predicted postacute phase anaemia after aSAH. METHODS: We developed a novel nomogram for aSAH patients to predict postacute phase anaemia (3 days after occurrence of aSAH, prior to discharge) on the basis of demographic information, imaging, type of treatment, aneurysm features, blood tests and clinical characteristics. We designed the model from a development cohort and tested the nomogram in external and prospective validation cohorts. We included 456 aSAH patients from The First Affiliated Hospital for the development, 220 from Sanmen People's Hospital for external validation and a prospective validation cohort that included 13 patients from Hangzhou Red Cross Hospital. We assessed the performance of the nomogram via concordance statistics and evaluated the calibration of predicted anaemia outcome with observed anaemia occurrence. RESULTS: Variables included in the nomogram were age, treatment method (open surgery or endovascular therapy), baseline haemoglobin level, fasting blood glucose level, systemic inflammatory response syndrome score on admission, Glasgow Coma Scale score, aneurysm size, prothrombin time and heart rate. In the validation cohort, the model for prediction of postacute phase anaemia had a c-statistic of 0.910, with satisfactory calibration (judged by eye) for the predicted and reported anaemia outcome. Among forward-looking forecasts, our predictive model achieved an 84% success rate, which showed that it has some clinical practicability. CONCLUSIONS: The developed and validated nomogram can be used to calculate individualised anaemia risk and has the potential to serve as a practical tool for clinicians in devising improved treatment strategies for aSAH.