JOURNAL/nrgr/04.03/01300535-202407000-00033/figure1/v/2026-05-11T120643Z/r/image-tiff Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier. However, the potential links between them following ischemic stroke remain largely unknown. The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway. Meanwhile, Wnt/β-catenin pathway activation by the pharmacological inhibitor, TWS119, relieved oxidative stress, increased the levels of cytochrome P450 1B1 (CYP1B1) and tight junction-associated proteins (zonula occludens-1 [ZO-1], occludin and claudin-5), as well as brain microvascular density in cerebral ischemia rats. Moreover, rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress, suppression of the Wnt/β-catenin pathway, aggravated cell apoptosis, downregulated CYP1B1 and tight junction protein levels, and inhibited cell proliferation and migration. Overexpression of β-catenin or knockdown of β-catenin and CYP1B1 genes in rat brain microvascular endothelial cells at least partly ameliorated or exacerbated these effects, respectively. In addition, small interfering RNA-mediated β-catenin silencing decreased CYP1B1 expression, whereas CYP1B1 knockdown did not change the levels of glycogen synthase kinase 3β, Wnt-3a, and β-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivation/reoxygenation. Thus, the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling, and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress, increased tight junction levels, and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

Purpose: The study aims to investigate, using anodal transcranial direct current stimulation (A-tDCS), over which site, the left lip region of primary motor cortex (M1) or the Broca's area, there would be better recovery from apraxia of speech (AoS) in patients with poststroke aphasia and to examine for altered activation in speech-related areas after tDCS with nonlinear electroencephalography (EEG). Method: Fifty-two patients with AoS were randomized into A-tDCS over the left M1 (A-tDCS-M1), Broca's area, and sham tDCS groups who underwent 10 sessions of tDCS and speech treatment for 5 days. The EEG nonlinear index of approximate entropy was calculated for 6 subjects in each group before and after treatment. Results: After treatment, the change in speech-language performance improved more significantly in the A-tDCS-M1 group than the other 2 groups ( p < .05). EEG approximate entropy indicated that both A-tDCS groups could activate the stimulated sites; the improvement in the A-tDCS-M1 group was correlated with high activation in the dorsal lateral prefrontal cortex and Broca's areas of the left hemisphere in addition to the stimulated site. Conclusion: A-tDCS over the left M1 can improve the speech function in patients with poststroke aphasia and severe AoS and excite and recruit more areas in the motor speech network.

Background: Substantial evidence suggests that immunoproteasome is implicated in the various neurological diseases such as stroke, multiple sclerosis and neurodegenerative diseases. However, whether the immunoproteasome itself deficiency causes brain disease is still unclear. Therefore, the aim of this study was to explore the contribution of the immunoproteasome subunit low molecular weight protein 2 (LMP2) in neurobehavioral functions. Methods: Male LMP2 gene completed knockout (LMP2-KO) and littermate wild type (WT) Sprague–Dawley (SD) rats aged 12-month-old were used for neurobehavioral testing and detection of proteins expression by western blotting and immunofluorescence. A battery of neurobehavioral test tools including Morris water maze (MWM), open field maze, elevated plus maze were used to evaluate the neurobehavioral changes in rats. Evans blue (EB) assay, Luxol fast blue (LFB) and Dihydroethidium (DHE) staining were applied to explore the blood–brain barrier (BBB) integrity, brain myelin damage and brain intracellular reactive oxygen species (ROS) levels, respectively. Results: We firstly found that LMP2 gene deletion did not cause significantly difference in rats’ daily feeding activity, growth and development as well as blood routine, but it led to metabolic abnormalities including higher levels of low-density lipoprotein cholesterol, uric acid and blood glucose in the LMP2-KO rats. Compared with the WT rats, LMP2-KO rats displayed obviously cognitive impairment and decreased exploratory activities, increased anxiety-like behavior and without strong effects on gross locomotor abilities. Furthermore, multiple myelin loss, increased BBB leakage, downregulation of tight junction proteins ZO-1, claudin-5 and occluding, and enhanced amyloid-β protein deposition were observed in brain regions of LMP2-KO rats. In addition, LMP2 deficiency significantly enhanced oxidative stress with elevated levels of ROS, caused the reactivation of astrocytes and microglials and markedly upregulated protein expression levels of interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), IL-6 and tumor necrosis factor-α (TNF-α) compared to the WT rats, respectively. Conclusion: These findings highlight LMP2 gene global deletion causes significant neurobehavioral dysfunctions. All these factors including metabolic abnormalities, multiple myelin loss, elevated levels of ROS, increased BBB leakage and enhanced amyloid-β protein deposition maybe work together and eventually led to chronic oxidative stress and neuroinflammation response in the brain regions of LMP2-KO rats, which contributed to the initial and progress of cognitive impairment.

To assess the diagnostic value of serum NLRP3 inflammasome and occludin levels in predicting hemorrhagic transformation (HT) and functional outcomes in acute ischemic stroke (AIS). AIS patients and matched controls were enrolled between June and November 2021. Serum biomarkers were measured and correlated with infarct volume, stroke severity, HT occurrence, and prognosis. Predictive performance was evaluated using logistic regression and ROC curves. A total of 156 AIS patients and 55 controls were included. AIS patients showed significantly elevated serum NLRP3 (56.59 pg/mL vs. 33.24 pg/mL) and occludin levels (97.42 ng/mL vs. 44.54 ng/mL) (both p <0.001). Both biomarkers correlated positively with infarction volume and NIHSS scores. HT occurred in 19.2% of patients, who exhibited markedly higher NLRP3 and occludin levels (both p<0.001). NLRP3 levels differed significantly between HI and PH subtypes (p = 0.042). Logistic regression identified infarct volume, creatinine, reperfusion therapy, and NLRP3 as independent predictors of HT. Poor functional outcomes were associated with older age, atrial fibrillation, HT, larger infarcts, higher NIHSS scores, and elevated serum biomarkers (all p <0.05). Age, NIHSS, LDL-C, and NLRP3 independently predicted prognosis. The optimal NLRP3 cut-off for predicting HT was 80.86 pg/mL (AUC 0.911), and for poor prognosis 82.75 pg/mL (AUC 0.663). Combining NLRP3 with NIHSS significantly enhanced prognostic accuracy (AUC 0.903). Elevated serum NLRP3 inflammasome levels represent a promising biomarker for predicting HT and unfavorable outcomes in AIS patients.