Ischemia–reperfusion (I/R) injury induces the generation of reactive oxygen species (ROS), which results in a poor prognosis for ischemic stroke patients. This study was designed to evaluate the time course of expression of the Nox family, a major source of ROS, and whether melatonin, a potent scavenger of ROS, influences these parameters in a rat model of cerebral I/R caused by middle cerebral artery occlusion (MCAO). After 2‐hr occlusion, the filament was withdrawn to allow reperfusion. At 0, 3, 6, 12, 24, and 48 hr after reperfusion, brain tissue samples were obtained for assays. Among the Nox family, the mRNA and protein levels of Nox2 and Nox4 were increased both in the ischemic hemisphere and contralateral counterpart in the experimental I/R rats at 0 hr after reperfusion, peaked at 3 hr, and then returned to the basal level at 24 hr. Double‐immunofluorescence staining further confirmed the expressions of Nox2 and Nox4 in three major types of brain cells, including neurons, astrocytes, and endothelial cells. In addition, melatonin (5 mg/kg) or its vehicle was injected intraperitoneally at 0.5 hr before MCAO. Compared with I/R + vehicle group, melatonin pretreatment diminished the increased expression of Nox2 and Nox4, reduced ROS levels, and inhibited cell apoptosis. Our findings suggested that the inhibition of Nox2 and Nox4 expressions by melatonin may essentially contribute to its antioxidant and anti‐apoptotic effects during brain I/R.

The goal of this study was to examine NOX2 and NOX4 expression in clinical samples of patients with traumatic brain injury (TBI), and to explore the correlation of NOX2 and NOX4 expression with the severity of injury, duration of injury, and prognosis. Brain samples of 20 TBI patients within 1 cm of the contusion site were collected and grouped based on duration of injury, Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS), and immunofluorescence staining were performed to examine the expression levels of NOX2 and NOX4 in the neurons and astrocytes. We found that the expression level of NOX2 in neurons and positive rate of NOX2 expression in astrocytes peaked at 12-24 and 6-12 h after injury, respectively. The expression level of NOX4 in neurons peaked at 24-48 h, and the positive rate of NOX4 expression gradually increased with prolonged injury. We also found that the higher the GCS score, the lower the expression levels of NOX2 and NOX4 in neurons was, while higher the GCS score, the lower the positive rate of NOX4 expression in astrocytes was and the higher the GOS grade, the lower the positive rate of expression in astrocytes was. In conclusion, NOX2 and NOX4 expressions significantly increase at an early stage after TBI, and abnormal expressions of NOX2 and NOX4 are correlated to patient prognosis to certain extent.

Delayed reendothelialization and intimal hyperplasia (IH) contribute to the failure of vascular interventions. Curcumin (Cur) has been used for various types of diseases with antioxidant, antiproliferative and anti-inflammatory effects. However, investigations involving the application of Cur in inhibiting IH are limited. The aim of the present study was to evaluate the potential therapeutic effects of Cur and its underlying mechanisms on a rat model of carotid artery (CA) intimal injury. In vitro, an endothelial cell (EC) migration assay was conducted using cultured primary human umbilical vein endothelial cells (HUVECs) that were exposed to Cur. In vivo, CA angioplasty injury was used to generate a rat model of intimal injury. CAs were collected at 3 days, and 1 and 4 weeks after injury, respectively, for western blot analysis and double-immunofluorescence analyses, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, oxidative stress indicator analysis and hematoxylin and eosin staining of the neointima. In vivo, Cur significantly enhanced the migration and healing of HUVECs and simultaneously promoted microtubule-associated protein light chain 3-II (LC3-II) expression when HUVECs were subjected to an artificial scratch. In vitro, endangium from the Cur-treated rats exhibited a significantly reduced number of apoptotic ECs and oxidative stress level compared to that of the sham group. In addition, Cur treatment markedly improved quantification of the LC3-II concomitant with the downregulation of p62 in the injured CA. At 1 week following injury, sizable neointimal lesions had developed, although prominent intima thickening was not observed. At 4 weeks, apparent hemadostenosis occurred resulting from the exorbitance IH. Cur treatment markedly reduced the thickness of the neointimal lesion. It is noteworthy that high-dose Cur may have exerted more significant effects than low-dose Cur. Cur can potentially become a therapeutic drug for angiostenosis by imparting a protective effect that accelerates reendothelialization and ameliorates IH and was mediated by its pro-autophagic effect.

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We attempt to generate a definition of delayed perihematomal edema expansion (DPE) and analyze its time course, risk factors, and clinical outcomes. A multi-cohort data was derived from the Chinese Intracranial Hemorrhage Image Database (CICHID). A non-contrast computed tomography (NCCT) -based deep learning model was constructed for fully automated segmentation hematoma and perihematomal edema (PHE). Time course of hematoma and PHE evolution correlated to initial hematoma volume was volumetrically assessed. Predictive values for DPE were calculated through receiver operating characteristic curve analysis and were tested in an independent cohort. Logistic regression analysis was utilized to identify risk factors for DPE formation and poor outcomes. The test cohort’s Dice scores of lesion segmentation were 0.877 and 0.642 for hematoma and PHE, respectively. Overall, 1201 patients were enrolled for time-course analysis of ICH evolution. A total of 312 patients were further selected for DPE analysis. Time course analysis showed the growth peak of PHE approximately concentrates in 14 days after onset. The best cutoff for DPE to predict poor outcome was 3.34 mL of absolute PHE expansion from 4-7 days to 8-14 days (AUC=0.784, sensitivity=72.2%, specificity=81.2%), and 3.78 mL of absolute PHE expansion from 8-14 days to 15-21 days (AUC=0.682, sensitivity=59.3%, specificity=92.1%) in the derivation sample. Patients with DPE was associated with worse outcome (OR: 12.340, 95%CI: 6.378-23.873, P<0.01), and the larger initial hematoma volume (OR: 1.021, 95%CI: 1.000-1.043, P=0.049) was the significant risk factor for DPE formation. This study constructed a well-performance deep learning model for automatic segmentations of hematoma and PHE. A new definition of DPE was generated and is confirmed to be related to poor outcomes in ICH. Patients with larger initial hematoma volume have a higher risk of developing DPE formation.

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Background Approximately 1/3 of spontaneous intracerebral hemorrhage (sICH) patients did not know the onset time and were excluded from studies about time-dependent treatments for hyperacute sICH. Aims To help clinicians explore the benefit of time-dependent treatments for unclear-onset patients, we presented artificial intelligence models to identify onset time using non-contrast computed tomography (NCCT) based on weakly supervised multitask learning (WS-MTL) structure. Methods The patients with reliable symptom onset time (strong label) or repeat CT (weak label) were included and split into training set and test set (internal and external). The WS-MTL structure utilized strong and weak labels simultaneously to improve performance. The models included three binary classification models for classifying whether NCCT acquired within 6, 8 or 12 hours for different treatments measured by area under curve (AUC), and a regression model for determining the exact onset time measured by mean absolute error (MAE). The generalizability of models was also explored in comprehensive analysis. Results 4 004 patients with 10 780 NCCT scans were included. The performance of WS-MTL classification model showed high accuracy, and that of regression model was satisfactory in ≤ 6 hours subgroup. In comprehensive analysis, the WS-MTL showed better performance for larger hematomas and thinner scans. And the performance improved effectively as training amounts increasing and could be improved steadily through retraining. Conclusions The WS-MTL models showed good performance and generalizability. Considering the large number of unclear-onset sICH patients, it may be worth to integrate the WS-MTL model into clinical practice to identify the onset time.

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