Background: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Prediction of penumbra existence after AIS is crucial for making decision on reperfusion therapy. Yet a fast, inexpensive, simple, and noninvasive predictive biomarker for the poststroke penumbra with clinical translational potential is still lacking. We aim to investigate whether the CircOGDH (circular RNA derived from oxoglutarate dehydrogenase) is a potential biomarker for penumbra in patients with AIS and its role in ischemic neuronal damage. Methods: CircOGDH was screened from penumbra of middle cerebral artery occlusion mice and was assessed in plasma of patients with AIS by quantitative polymerase chain reaction. Magnetic resonance imaging was used to examine the penumbra volumes. CircOGDH interacted with miR-5112 (microRNA-5112) in primary cortical neurons was detected by fluorescence in situ hybridization, RNA immunoprecipitation, and luciferase reporter assay. Adenovirus-mediated CircOGDH knockdown ameliorated neuronal apoptosis induced by COL4A4 (Gallus collagen, type IV, alpha IV) overexpression. Transmission electron microscope, nanoparticle tracking analysis, and Western blot were performed to confirm exosomes. Results: CircOGDH expression was dramatically and selectively upregulated in the penumbra tissue of middle cerebral artery occlusion mice and in the plasma of 45 patients with AIS showing a 54-fold enhancement versus noncerebrovascular disease controls. Partial regression analysis revealed that CircOGDH expression was positively correlated with the size of penumbra in patients with AIS. Sequestering of miR-5112 by CircOGDH enhanced COL4A4 expression to elevate neuron damage. Additionally, knockdown of CircOGDH significantly enhanced neuronal cell viability under ischemic conditions. Furthermore, the expression of CircOGDH in brain tissue was closely related to that in the serum of middle cerebral artery occlusion mice. Finally, we found that CircOGDH was highly expressed in plasma exosomes of patients with AIS compared with those in noncerebrovascular disease individuals. Conclusions: These results demonstrate that CircOGDH is a potential therapeutic target for regulating ischemic neuronal viability, and is enriched in neuron-derived exosomes in the peripheral blood, serving as a predictive biomarker of penumbra in patients with AIS.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and communication between the gut and brain (the gut-brain axis) has been found to be essential in behavior and cognitive function. However, the exact mechanisms underlying microbiota dysbiosis in PD progression have not yet been elucidated. Our study aimed to investigate the correlation between gut microbiota disturbances and feces metabolic disorders in PD. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD models and observed mice's motor symptoms, dopaminergic (DA) neuron death, and gastrointestinal dysfunction. To identify alterations in microbiota and metabolome, feces were collected from mice and analyzed using 16 S ribosomal RNA sequencing feces metabolomics. Pearson analysis was utilized to investigate correlations between the abundances of gut microbiota components and the levels of gut microbiota metabolites, displaying their interaction networks. Our findings revealed a significant increase in Desulfobacterota in the PD mouse model and 151 differentially expressed fecal metabolites between PD and vehicle mice. Moreover, Pearson correlation analysis suggested that the protective factor N-acetyl-L-leucine (NALL) may be associated with neuroinflammation in the striatum and substantia nigra, which also had a negative relationship with the concentration of Desulfobacterota. Additionally, we found that oral administration of NALL alleviated MPTP-induced Motor Impairments and DA neuronal deficits. All in all, we concluded that the decrease of NALL might lead to a significant increase of Desulfobacterota in the MPTP model mouse and subsequently result in the damage of DA neurons via the gut-brain aix pathway.

Background and Purpose: Modified Thrombolysis in Cerebral Infarction score (mTICI) ≥2b is defined as successful reperfusion. However, mTICI has rarely been correlated with dynamic perfusion imaging postendovascular therapy for acute stroke. We aimed to study the proportion of tissue optimal reperfusion (TOR) postendovascular therapy across different grades of mTICI. Methods: We conducted a single-center retrospective analysis of patients with acute ischemic strokes who had endovascular therapy between 2018 and 2019. Computer tomography perfusion or magnetic resonance perfusion was performed before and after endovascular therapy. Tmax+6 volume reduction of >90% was defined as TOR. Comparisons of proportions of TOR in different grades of mTICI were performed. In the present study, the requirement for informed consents was waived. Results: Eighty-two patients were included. The difference in the proportion of TOR for TICI categories was statistically significant (mTICI score 0, 0%, mTICI score 2A, 0%, mTICI score 2b, 50.0%, mTICI score 2c, 80.0%, mTICI score 3, 81.3%, χ ² =14.035, P =0.003). Multivariable logistic regression showed that lower age (odds ratio, 0.932, P =0.017), onset-to-tissue-type plasminogen activator time (odds ratio, 0.980, P =0.005) and TOR (odds ratio, 8.764, P =0.031) were associated with favorable functional outcome. Conclusions: The proportion of TOR achieved by mTICI score of 2b was significantly lower than mTICI score of 2c and mTICI score of 3. TOR was associated with favorable functional outcome, and the degree of reperfusion was more strongly correlated with outcomes than the mTICI scores.

Background: In patients with acute stroke who undergo endovascular thrombectomy, the relative prognostic power of computed tomography perfusion (CTP) parameters compared with multiphase CT angiogram (mCTA) is unknown. We aimed to compare the predictive accuracy of mCTA and CTP parameters on clinical outcomes. Methods: We included patients with acute ischemic stroke who had anterior circulation large vessel occlusion within 24 hours of onset in Melbourne Brain Centre at the Royal Melbourne Hospital. All patients underwent CTP for endovascular thrombectomy, and the mCTA collateral score was determined using CTP-reconstructed mCTA images. The primary outcome was 90-day functional outcomes defined by modified Rankin Scale. Multivariable logistic regression models analyzed associations between mCTA and CTP parameters and 90-day functional outcomes. The ability to discriminate 90 days-functional outcomes was compared between mCTA collateral score and CTP parameters using receiver operating curve analysis and C statistics. Results: One hundred and twenty patients were included. The median age was 69 years (interquartile range, 60–79), the median baseline National Institutes of Health Stroke Scale score was 14 (interquartile range, 9–19). The baseline ischemic core volume, defined by CTP-based relative cerebral blood flow <30%, was associated with excellent functional outcome (modified Rankin Scale score 0–1; odds ratio, 0.942 [−0.897 to −0.989]; P =0.015) and poor functional outcome (modified Rankin Scale score 5–6; odds ratio, 1.032 [1.007–1.056]; P =0.010) at 90 days in the analysis of multivariable regression. There was no significant association between the mCTA score and excellent functional outcome ( P =0.58) or poor functional outcome ( P =0.155). The relative cerebral blood flow <30%-based regression model best fit the data for the 90-day poor functional outcome (C statistic, 0.834). Conclusions: The CTP-based ischemic core volume may provide better discrimination for 90-day functional outcomes for patients with acute stroke undergoing endovascular thrombectomy than the mCTA collateral score.

Symtomatic hemorrhagic transformation(sHT) was defined as any intracerebral hemorrhage that combined with clinical deterioration. While recent studies showed low rates of sHT in large core ischemic strokes treated with endovascular thrombectomy (EVT), the specific impact of core size on overall hemorrhagic transformation (HT) remains unclear. We aim to investigate the relationship between ischemic core size and development of HT post thrombectomy. This prospective study enrolled acute ischemic stroke (AIS) patients with anterior large vessel occlusion undergoing EVT who had baseline MRI from 2017 to 2019. Pre-EVT Arterial Spin Labeling (ASL) and Diffusion-Weighted Imaging (DWI) scans were performed for volume calculations. Primary outcome was HT assessed within 72 h post EVT. Multivariable logistic regression was used to analyze the associations between baseline DWI and ASL volumes and HT occurrence. Discriminative ability for HT was compared using receiver operating curve analysis (c-statistic). We included 101 patients (median age: 64 [IQR 56-74] years, baseline NIHSS 13 [IQR 9-16]). Median DWI and ASL volume were 21.0 ml [IQR 8.3-47.2] and 105 ml [59.5-172.9], respectively. 16.8 % recieved intravenous thrombolysis before EVT. HT occurred in 36.6 % of patients, including 16.8 % with sHT. Baseline DWI volume was independently associated with HT (OR = 1.030, 95 % CI 1.008 to 1.053, P = 0.009), while ASL volume wasn't statistically significant(P = 0.330). The DWI model was superior to ASL model in predicting HT within 72 h (c-statistic, 0.787).Neither DWI (P = 0.149) nor ASL volume (P = 0.834) effectively indicated sHT. DWI-based ischemic core volume correlates significantly with HT within 72 h post successful thrombectomy. This highlights the potential clinical utility of DWI in guiding treatment decisions for this population.

Background: Intracranial atherosclerotic stenosis is a leading cause of ischemic stroke and recurrent events due to plaque instability. High‐resolution magnetic resonance imaging identifies plaque enhancement as a key marker of instability. This study evaluated the efficacy of combined high‐intensity statins and proprotein convertase subtilisin/kexin type 9 inhibitors in plaque stabilization. Methods: In this prospective, single‐arm study, patients with acute stroke and intracranial atherosclerotic stroke in the M1 segment of the middle cerebral artery or basilar artery were enrolled. After 24 weeks of intensive statin and evolocumab therapy, high‐resolution magnetic resonance imaging assessments of intracranial vessels were conducted at baseline and follow‐up. The primary end point was the change in stenosis degree; secondary end points included changes in plaque enhancement (contrast ratio) and plaque burden. Results: Thirty‐six patients (median age, 58 years) participated. After therapy, stenosis decreased from 75.9% (interquartile range, 69.5%–84.8%) to 65.3% (interquartile range, 53.8%–75.0%; P <0.001). Contrast ratio grades and contrast volume decreased significantly ( P <0.001), and lumen area increased (from 1.03 mm ² [interquartile range, 0.59–1.72 mm ² ] to 2.08 mm ² [interquartile range, 1.00–3.10 mm ² ]; P <0.001). No significant changes were observed in wall area, wall area index, or remodeling index. A notable correlation between the decrease in low‐density lipoprotein cholesterol/apolipoprotein B ratio and reduction in contrast volume was observed. Conclusions: Combining proprotein convertase subtilisin/kexin type 9 inhibitors with high‐intensity statins may improve plaque stability and reduce lumen stenosis in patients with intracranial atherosclerotic stenosis. Larger randomized controlled trials are needed to confirm these findings. Registration: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR2200058029.