The genetic transcription pro le of brain ischemic and reperfusion injury remains elusive. To address this, we used an integrative analysis approach including differentially expressed genes (DEGs) analysis, weighted-gene co-expression network analysis (WGCNA), and pathway and biological processes analysis to analyze data from the microarray studies of nine mice and ve rats after middle cerebral artery occlusion (MCAO), and six primary cell transcriptional datasets in the Gene Expression Omnibus (GEO). We identi ed reperfusion as the main confounding factor in gene pro le changes. Our analyses of pathway and biological processes revealed upregulated functional modules involved in in ammatory disequilibrium and thrombus formation. Astrocytes, microglia, and macrophages were the main contributors of in ammation-related gene changes. Novel core hubs implicated in negative regulation of in ammation (Zfp36, Nfkbiz, and Maff) were identi ed and validated. Collectively, these results expand our knowledge of the genetic pro le involved in brain ischemia and reperfusion, highlighting the crucial role of in ammatory disequilibrium in brain ischemia.

Cerebral small vessel disease (CSVD) is a slowly progressive disease, often accompanied by stroke, and results in dementia, depression, and cognitive impairment. It was already known that calcium and phosphorus metabolism (CPM) disorders were associated with vascular-related adverse events. The risk factors of CSVD and the relationship between serum calcium (Ca), phosphorus (P), calcium-phosphate product (Ca × P), and CSVD in patients with stroke without CPM disorders are still obscure. In our study, 528 patients with stroke without CPM disorders were enrolled in a cohort from a consecutive hospital-based stroke registry, with 488 patients with CSVD as cases and 140 without CSVD as controls. The patients with CSVD were further sub-grouped into lacunes, white matter hyperintensities (WMHs), and cerebral microbleeds (CMBs). By applying univariate and multivariate logistic regression analysis, the following novel findings were obtained: (i) up to 76.19% of patients with stroke had signs of CSVD, and lacunes are the most common subtype. Notably, 22.96% of patients with CSVD had multiple subtypes coexisted. (ii) Compared with patients without CSVD, patients with CSVD had higher levels of age, rate of hypertension or diabetes, serum Ca, P, Ca × P, and lower levels of white blood cell (WBC) and hemoglobin (HB). (iii) We developed 2 predictive models and nomograms for predicting CSVD, in addition to the known factors (age and hypertension). The levels of P and Ca × P were positively correlated with the risk of CSVD (P: OR = 3,720.401, 95% CI (646.665–21,404.249); Ca × P: OR = 1.294, 95% CI (1.222–1.370)). (iv) The models were further validated in subtypes of CSVD, including lacunes, WMHs, and CMBs, and the results were still valid among the subtypes. In summary, CSVD was highly prevalent in patients with stroke, and high serum P and Ca × P are potential risk factors of CSVD and all subtypes including lacunes, WMHs, and CMBs.

Cerebral small vessel disease (CSVD) is a slowly progress disease, often accompanied by stroke, and result in dementia, depression, cognitive impairment, etc. It had already known that calcium and phosphorus metabolism (CPM) disorders were associated with vascular related adverse events. Serum Ca, P, Ca×P are the most commonly used indicators of CPM in clinical. The risk factors of CSVD and the relationship of serum Ca, P, Ca×P and CSVD in stroke patients who do not have CPM disorders are still obscure. We enrolled 488 CSVD patients in a cohort from a consecutive hospital-based stroke registry, and further sub-grouped them into lacunes, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and matched them to 140 stroke patients without CSVD as controls. CSVD patients had higher levels of serum Ca, P, Ca×P. We developed 2 predictive models and nomograms (incorporating age, hypertension, P or Ca×P, respectively) for CSVD patients. The prediction and calibration power were good. Area under the curve (AUC) was 0.855, 0.851, respectively. P value of Hosmer-Lemeshow goodness of fit (H-L) test was 0.689, 0.698, respectively. P and Ca×P were positive correlated with CSVD, with OR 3720.401 (646.665-21404.249), 1.294 (1.222-1.370), respectively. We further validated the models in lacunes, WMHs, and CMBs, and found models were still valid in these 3 subtypes. In summary, a high serum P or Ca×P are associated with an increased risk of CSVD in stroke patients who without CPM disorders.

The genetic transcription profile of brain ischemic and reperfusion injury remains elusive. To address this, we used an integrative analysis approach including differentially expressed genes (DEGs) analysis, weighted-gene co-expression network analysis (WGCNA), and pathway and biological processes analysis to analyze data from the microarray studies of nine mice and five rats after middle cerebral artery occlusion (MCAO), and six primary cell transcriptional datasets in the Gene Expression Omnibus (GEO). We identified reperfusion as the main confounding factor in gene profile changes. Our analyses of pathway and biological processes revealed upregulated functional modules involved in inflammatory disequilibrium and thrombus formation. Astrocytes, microglia, and macrophages were the main contributors of inflammation-related gene changes. Novel core hubs implicated in negative regulation of inflammation (Zfp36, Nfkbiz, and Maff) were identified and validated. Collectively, these results expand our knowledge of the genetic profile involved in brain ischemia and reperfusion, highlighting the crucial role of inflammatory disequilibrium in brain ischemia.

Cerebral small vessel disease (CSVD) is a slowly progress disease, often accompanied by stroke, and result in dementia, depression, cognitive impairment, etc. It had already known that calcium and phosphorus metabolism (CPM) disorders were associated with vascular related adverse events. Serum Ca, P, Ca×P are the most commonly used indicators of CPM in clinical. The risk factors of CSVD and the relationship of serum Ca, P, Ca×P and CSVD in stroke patients who do not have CPM disorders are still obscure. We enrolled 488 CSVD patients in a cohort from a consecutive hospital-based stroke registry, and further subgrouped them into lacunes, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and matched them to 140 stroke patients without CSVD as controls. CSVD patients had higher levels of serum Ca, P, Ca×P. We developed 2 predictive models and nomograms (incorporating age, hypertension, P or Ca×P, respectively) for CSVD patients. The prediction and calibration power were good. Area under the curve (AUC) was 0.855, 0.851, respectively. P value of Hosmer-Lemeshow goodness of t (H-L) test was 0.689, 0.698, respectively. P and Ca×P were positive correlated with CSVD, with OR 3720.401 (646.665-21404.249), 1.294 (1.222-1.370), respectively. We further validated the models in lacunes, WMHs, and CMBs, and found models were still valid in these 3 subtypes. In summary, a high serum P or Ca×P are associated with an increased risk of CSVD in stroke patients who without CPM disorders.