Dietary Flavonoid Intake and Carotid Calcification in Patients with Ischemic Stroke.

INTRODUCTION: Owing to the antioxidant and anti-inflammatory effects, flavonoids can influence the initiation and development of atherosclerosis, but the underlying mechanisms remain largely undetermined. This study aimed to evaluate the associations between dietary flavonoids and carotid calcification in patients with ischemic stroke. METHODS: This study screened consecutive patients with ischemic stroke via Nanjing Stroke Registry Program from February 2016 to April 2021. A semiquantitative food frequency questionnaire was used to evaluate dietary consumption of flavonoids and other nutritional components. Presence and degree of carotid calcification were determined according to Agatston scores on computer tomography angiography. Logistic regression was performed to evaluate the association between dietary flavonoids (total flavonoids, flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, and isoflavones) and carotid calcification. RESULTS: Of the 601 enrolled patients, 368 (61.2%) were detected with carotid calcification. Patients with high intake of total flavonoids (the fifth quintile) had a 52% lower carotid calcification risk than those with low intake (the first quintile; odds ratio [OR] = 0.48; 95% confidence interval [CI], 0.26-0.90; p = 0.007 for trends) after adjusting for major confounders. Patients with high intake of flavan-3-ols (the fifth quintile) had a 51% lower carotid calcification risk than those with low intake (the first quintile; OR = 0.49; 95% CI, 0.25-0.97; p = 0.016 for trends). CONCLUSION: Dietary flavonoid intake is associated with carotid calcification, and, therefore, may influence the risk of stroke occurrence and recurrence.

Detecting prokaryote-specific gene and other bacterial signatures in thrombi from patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Microbial infection has been associated with thrombogenesis. This study aimed to detect bacterium-specific genes and other signatures in thrombi from patients with acute ischemic stroke and to relate these signatures to clinical characteristics. METHODS: Blood samples were collected before thrombectomy procedures, and thrombus samples were obtained during the procedure. Identification and classification of bacteria in the samples were accomplished using 16 S rRNA gene sequencing. Bacterium-specific structures were observed with transmission electron microscopy. Bacterium-specific biomarkers were detected through immunohistochemical staining. RESULTS: 16 S rRNA gene was detected in 32.1% of the thrombus samples from 81 patients. Bacillus (0.04% vs. 0.00046%, p = 0.003), Parabacteroides (0.20% vs. 0.09%, p = 0.029), Prevotella (1.57% vs. 0.38%, p = 0.010), Streptococcus (1.53% vs. 0.29%, p = 0.001), Romboutsia (0.18% vs. 0.0070%, p = 0.029), Corynebacterium (1.61% vs. 1.26%, p = 0.026) and Roseburia (0.53% vs. 0.05%, p = 0.005) exhibited significantly higher abundance in thrombi compared to arterial blood. Bacteria-like structures were observed in 22 (27.1%), while whole bacteria-like structures were observed in 7 (8.6%) thrombi under transmission electron microscopy. Immunohistochemical staining detected bacterium-specific monocyte/macrophage markers in 51 (63.0%) out of 81 thrombi. Logistic regression analysis indicated that alcohol consumption was associated with a higher bacteria burden in thrombi (odds ratio = 3.19; 95% CI, 1.10-9.27; p = 0.033). CONCLUSION: Bacterial signatures usually found in the oral cavity and digestive tract were detected in thrombi from patients with ischemic stroke. This suggests a potential involvement of bacterial infection in the development of thrombosis. Long-term alcohol consumption may potentially enhance this possibility.

The Association between Migraine and Fetal-Type Posterior Cerebral Artery in Patients with Ischemic Stroke.

OBJECTIVE: The aim of the study was to determine if migraine is associated with fetal-type posterior cerebral artery (PCA) in patients with ischemic stroke. METHOD: In this cross-sectional study, patients with acute ischemic stroke were enrolled from two hospitals. The history of migraine headache was evaluated during a face-to-face interview. The variants of fetal-type PCA were assessed with MRA, CTA, or DSA. Patients with and without migraine were compared in terms of fetal-type PCA status and other clinic characteristics. Multivariate logistic regression analyses were performed to adjust for confounders and provide risk estimates for observed associations. RESULT: In 750 patients qualified for analysis, 85 (11.3%) were determined with migraine. Patients with migraine had a higher proportion of female gender (51.8% vs. 31.0%, p < 0.001), hypertension (72.9% vs. 57.7%, p = 0.007), and fetal-type PCA (36.5% vs. 20.1%, p = 0.001), while lower proportion of current smoking (25.9% vs. 38.3%, p = 0.025) than patients without migraine. National Institutes of Health Stroke Scale (NIHSS) score (3 vs. 2, p = 0.016) was also higher in migraineurs than in non-migraineurs. After adjustment for confounders, fetal-type PCA status was independently associated with migraine (odds ratio [OR] = 2.06; 95% confidence interval [CI], 1.25-3.38; p = 0.005). Other factors associated to migraine included female gender (OR = 2.03; 95% CI, 1.13-3.62; p = 0.017), hypertension (OR = 1.97; 95% CI, 1.17-3.34; p = 0.011), and NIHSS score (OR = 1.08; 95% CI, 1.01-1.16; p = 0.018). CONCLUSION: Migraine was associated with fetal-type PCA in patients with ischemic stroke. This finding supported the hypothesis that vascular mechanisms get involved in the migraine-stroke association.

Chronic gastritis may predict risk of cerebral small vessel disease.

BACKGROUND AND PURPOSE: Chronic gastritis, especially that caused by helicobacter pylori (HP) infection, has been associated with increased risk of ischemic stroke. But the relationship between chronic gastritis and cerebral small vessel disease (CSVD) remains largely undetermined. This study aimed to determine the potential predictors for CSVD, with chronic gastritis and its proxies as alternatives. METHOD: Patients aged 18 years or older with indications for electronic gastroscopy were enrolled. Presence of CSVD was evaluated with brain magnetic resonance imaging (MRI) results. Degree of CSVD was scored according to established criteria. Logistic regression analysis was used for identifying possible risk factors for CSVD. RESULTS: Of the 1191 enrolled patients, 757 (63.6%) were identified as with, and 434 (36.4%) as without CSVD. Multivariate analysis indicated that patients with chronic atrophic gastritis had an increased risk for CSVD than those without (adjusted odds ratio = 1.58; 95% CI, 1.08-2.32; P < 0.05). CONCLUSIONS: Chronic atrophic gastritis is associated with the presence of CSVD. We should routinely screen the presence of CSVD for patients with chronic atrophic gastritis.

Extracellular vesicles carrying proinflammatory factors may spread atherosclerosis to remote locations.

Most cells involved in atherosclerosis release extracellular vesicles (EVs), which can carry bioactive substances to downstream tissues via circulation. We hypothesized that EVs derived from atherosclerotic plaques could promote atherogenesis in remote locations, a mechanism that mimics the blood metastasis of cancer. Ldlr gene knockout (Ldlr KO) rats were fed on a high cholesterol diet and underwent partial carotid ligation to induce local atherosclerosis. EVs were separated from carotid artery tissues and downstream blood of carotid ligation by centrifugation. MiRNA sequencing and qPCR were then performed to detect miRNA differences in EVs from rats with and without induced carotid atherosclerosis. Biochemical analyses demonstrated that EVs derived from atherosclerosis could increase the expression of ICAM-1, VCAM-1, and E-selectin in endothelial cells in vitro. EVs derived from atherosclerosis contained a higher level of miR-23a-3p than those derived from controls. MiR-23a-3p could promote endothelial inflammation by targeting Dusp5 and maintaining ERK1/2 phosphorylation in vitro. Inhibiting EV release could attenuate atherogenesis and reduce macrophage infiltration in vivo. Intravenously administrating atherosclerotic plaque-derived EVs could induce intimal inflammation, arterial wall thickening and lumen narrowing in the carotids of Ldlr KO rats, while simultaneous injection of miR-23a-3p antagomir could reverse this reaction. The results suggested that EVs may transfer atherosclerosis to remote locations by carrying proinflammatory factors, particularly miR-23a-3p.

Association between dietary antioxidant capacity and atherosclerotic carotid stenosis in patients with ischemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the relationship between dietary total antioxidant capacity (DTAC) and atherosclerotic carotid stenosis in patients with ischemic stroke. METHODS: Patients with acute ischemic stroke were consecutively enrolled. Daily food consumption was estimated by a semi-quantitative food frequency questionnaire (FFQ). DTAC was calculated based on classified food intake. Antioxidant potential value was measured by ferric-reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) methods. Evaluation of carotid artery stenosis was based on computed tomography angiography (CTA). Logistic regression was used to assess the relationship between DTAC and degree of carotid stenosis. RESULTS: Of the 608 enrolled, 232 patients (38.2%) had moderate or severe carotid stenosis. After adjusting for major confounding factors, FRAP (OR =0.640; 95% CI: 0.410-0.998; P =0.049) and ORAC (OR =0.625; 95% CI: 0.400-0.976; P =0.039) were associated with lower degree of carotid artery stenosis (third vs first tertile). Spearman analysis indicated that FRAP (r =-0.121, P =0.003) and ORAC (r =-0.147, P <0.001) were correlated with degree of carotid stenosis. CONCLUSIONS: DTAC may influence the initiation and development of atherosclerosis, and, therefore, the risk of ischemic stroke.

High-frequency repetitive transcranial magnetic stimulation (rTMS) protects against ischemic stroke by inhibiting M1 microglia polarization through let-7b-5p/HMGA2/NF-κB signaling pathway.

BACKGROUND: Microglia assume opposite phenotypes in response to ischemic brain injury, exerting neurotoxic and neuroprotective effects under different ischemic stages. Modulating M1/M2 polarization is a potential therapy for treating ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) held the capacity to regulate neuroinflammation and astrocytic polarization, but little is known about rTMS effects on microglia. Therefore, the present study aimed to examine the rTMS influence on microglia polarization and the underlying possible molecular mechanisms in ischemic stroke models. METHODS: Previously reported 10 Hz rTMS protocol that regulated astrocytic polarization was used to stimulate transient middle cerebral artery occlusion (MCAO) rats and oxygen and glucose deprivation/reoxygenation (OGD/R) injured BV2 cells. Specific expression levels of M1 marker iNOS and M2 marker CD206 were measured by western blotting and immunofluorescence. MicroRNA expression changes detected by high-throughput second-generation sequencing were validated by RT-PCR and fluorescence in situ hybridization (FISH) analysis. Dual-luciferase report assay and miRNA knock-down were applied to verify the possible mechanisms regulated by rTMS. Microglia culture medium (MCM) from different groups were collected to measure the TNF-α and IL-10 concentrations, and detect the influence on neuronal survival. Finally, TTC staining and modified Neurological Severity Score (mNSS) were used to determine the effects of MCM on ischemic stroke volume and neurological functions. RESULTS: The 10 Hz rTMS inhibited ischemia/reperfusion induced M1 microglia and significantly increased let-7b-5p level in microglia. HMGA2 was predicted and proved to be the target protein of let-7b-5p. HMGA2 and its downstream NF-κB signaling pathway were inhibited by rTMS. Microglia culture medium (MCM) collected from rTMS treated microglia contained lower TNF-α concentration but higher IL-10 concentration than no rTMS treated MCM, reducing ischemic volumes and neurological deficits of MCAO mice. However, knockdown of let-7b-5p by antagomir reversed rTMS effects on microglia phenotype and associated HMGA/NF-κB activation and neurological recovery. CONCLUSION: High-frequency rTMS could alleviate ischemic stroke injury through inhibiting M1 microglia polarization via regulating let-7b-5p/HMGA2/NF-κB signaling pathway in MCAO models.

Delayed Stroke Treatment during COVID-19 Pandemic in China.

BACKGROUND: Social distance, quarantine, pathogen testing, and other preventive strategies implemented during CO-VID-19 pandemic may negatively influence the management of acute ischemic stroke (AIS). OBJECTIVE: The current study aimed to evaluate the impacts of COVID-19 pandemic on treatment delay of AIS in China. METHODS: This study included patients with AIS admitted in 2 hospitals in Jiangsu, China. Patients admitted before and after the COVID-19 pandemic outbreak (January 31, 2020, as officially announced by the Chinese government) were screened to collect sociodemographic data, medical history information, and symptom onset status from clinical medical records and compared for pre- (measured as onset-to-door time [ODT]) and posthospital delay (measured as door-to-needle time [DNT]). The influencing factors for delayed treatment (indicated as onset-to-needle time >4.5 h) were analyzed with multivariate logistic regression analysis. RESULTS: A total of 252 patients were included, of which 153 (60.7%) were enrolled before and 99 (39.3%) after the COVID-19 pandemic. ODT increased from 202 min (interquartile range [IQR] 65-492) before to 317 min (IQR 75-790) after the COVID-19 pandemic (p = 0.001). DNT increased from 50 min (IQR 40-75) before to 65 min (IQR 48-84) after the COVID-19 pandemic (p = 0.048). The proportion of patients with intravenous thrombolysis in those with AIS was decreased significantly after the pandemic (15.4% vs. 20.1%; p = 0.030). Multivariate logistic regression analysis indicated that patients after COVID-19 pandemic, lower educational level, rural residency, mild symptoms, small artery occlusion, and transported by other means than ambulance were associated with delayed treatment. CONCLUSIONS: COVID-19 pandemic has remarkable impacts on the management of AIS. Both pre- and posthospital delays were prolonged significantly, and proportion of patients arrived within the 4.5-h time window for intravenous thrombolysis treatment was decreased. Given that anti-COVID-19 measures are becoming medical routines, efforts are warranted to shorten the delay so that the outcomes of stroke could be improved.

Impacts of in-hospital workflow on functional outcome in stroke patients treated with endovascular thrombectomy.

High-performance in-hospital workflow may save time and improve the efficacy of thrombectomy in patients with acute ischemic stroke. However, the optimal in-hospital workflow is far from being formulated, and the current models varied distinctly among centers. This study aimed to evaluate the impacts of in-hospital workflow on functional outcomes after thrombectomy. Patients were enrolled from a multi-center registry program in China. Based on in-hospital managing procedure and personnel involved, two workflow models, neurologist-dominant and non-neurologist-dominant, were identified in the participating centers. Favorable outcome was defined as a mRS score of ≤ 2 at 90 days of stroke onset. After patients being matched with propensity score matching (PSM) method, ratios of favorable outcomes and symptomatic intracerebral hemorrhage (sICH) were compared between patients with different workflow models. Of the 632 enrolled patients, 543 (85.9%) were treated with neurologist-dominant and 89 (14.1%) with non-neurologist-dominant model. 88 patients with neurologist-dominant model and 88 patients with non-neurologist-dominant model were matched with PSM. For the matched patients, no significant differences concerning the ratios of successful recanalization (92.0% vs 87.5%, P = 0.45), sICH (17.0% vs 14.8%, P = 0.85), favorable outcome (42.0% vs 42.0%, P = 1.00) were detected between patients with neurologist-dominant model and those with non-neurologist-dominant model. Patients with neurologist-dominant model had shorter door to puncture time (124 (86-172) vs 156 (120-215), P = 0.005), fewer passes of retriever (2 (1-3) vs 2 (1-4), P = 0.04), lower rate of > 3 passes (11.4% vs 28.4%, P = 0.004), and lower incidence of asymptomatic intracerebral hemorrhage rate (27.3% vs 43.2%, P = 0.045). Although the neurologist-dominant model may decrease in-hospital delay and risk of asymptomatic intracerebral hemorrhage, workflow models may not influence the functional outcome significantly after thrombectomy in patients with acute ischemic stroke.

Early Neurological Deterioration and Hypoperfusion Volume Ratio on Arterial Spin Labeling in Patients with Acute Ischemic Stroke.

BACKGROUND: Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used to quantify cerebral blood perfusion by labeling blood water as it flows throughout the brain. Hypoperfusion volume ratio (HVR) can be calculated using proportional hypoperfusion volume on ASL-based cerebral blood flow (CBF). This study aimed to explore the relation between HVR and early neurological deterioration (END) in AIS patients. SUBJECTS AND METHODS: Patients with AIS were recruited consecutively, and ASL and regular MRI scans were performed. HVR was calculated from 1.5 and 2.5s post labeling delay (PLD) ASL-CBF maps. END was defined as ≥2 points increment of NIHSS within 72 hours of stroke onset. Univariate and multivariate analysis were used to evaluate the relation between HVR and END. Receiver operating characteristic (ROC) curves were used to determine the ability of HVR in predicting END. RESULTS: Of the 52 enrolled patients, 18 (34.5%) were determined with END. In patients with END, the median hypoperfusion volume was 20 mL [Inter Quartile Range)IQR, 6-72.5 mL] at 1.5s PLD, and 11.2 mL (IQR, 5.3-26 mL) at 2.5s PLD; Sixteen (88.9%) patients had HVR ≥50%, and 13 (72.2%) patients hypoperfusion volume at 2.5s PLD ASL were greater than diffusion-weighted imaging (DWI) infarct volume. In patients without END, median hypoperfusion volume was 7 mL (IQR, 4-30 mL) at 1.5s PLD, and 4 mL (IQR, 1.5-8.5 mL) at 2.5s; Eleven (32.4%) patients had HVR ≥50%, and 10 (29.4%) patients hypoperfusion volume at 2.5s PLD ASL were greater than DWI infarct volume. The proportion of HVR ≥50% and hypoperfusion volume >DWI infarct volume were more frequent in patients with END than patients without (all P<0.001). After adjusted for age, admission NIHSS, proportion of hypoperfusion volume > DWI infarct and arterial transit artifact (ATA) by logistic regression analysis, HVR ≥50% (OR=13.1, P=0.003) was an independent risk factor for END. ROC analysis demonstrated that the HVR could predict END with an area under the curve of 0.794 (P=0.001). CONCLUSIONS: HVR obtained from the 1.5 and 2.5s PLD ASL may be a useful predictor of END in AIS. The value of HVR may be a marker for hemodynamic impairments.

Intravenous Thrombolysis before Thrombectomy may Increase the Incidence of Intracranial Hemorrhage inTreating Carotid T Occlusion.

BACKGROUND AND PURPOSE: Current evidence does not agree on the merits of direct and bridging thrombectomy. This study aimed to compare the safety and efficacy of direct thrombectomy (DT) and bridging thrombectomy (BT) in treating patients with acute ischaemic stroke due to carotid T occlusion. METHODS: Patients with stroke due to carotid T occlusion who were treated with DT or BT were retrospectively collected from four advanced stroke centres. Baseline characteristics and clinical outcomes were compared between the groups. Successful recanalization was defined by a modified thrombolysis in cerebral infarction (mTICI) score of 2b or 3. A favourable outcome was defined by a modified Rankin Scale (mRS) score of 0-2 at 90 days after stroke onset. Multivariable analysis was performed to control for potential confounders. RESULTS: Of the 111 enrolled patients, 57 (51.4%) patients were treated with DT, and 54 (48.6%) were treated with BT. Patients treated with DT had a shorter imaging to puncture (ITP) time (53 min versus 92 min, P<0.001) and symptom onset to puncture (OTP) time (198 min versus 218 min, P=0.045) than patients treated with BT. No significant difference was detected concerning the rate of successful recanalization (80.7% versus 77.8%, P=0.704) or a favourable outcome between patients treated with DT and BT (35.1% versus 33.3%, P=0.846). Patients treated with DT had a lower intracranial haemorrhage (ICH) rate (40.4% versus 59.3%, P=0.046), but the difference was not significant for symptomatic ICH (sICH, 12.3% versus 16.7%, P=0.511) or asymptomatic ICH (aICH, 28.1% versus 42.6%, P=0.109). After adjusting for potential confounding factors, the ratio of favorable prognosis, successful reperfusion, sICH and mortality did not differ between the two groups. However, there was a higher rate of ICH (OR=2.492, 95% CI 1.005 to 6.180, p=0.049) in the BT group as compared with the DT group. CONCLUSIONS: DT seems equivalent to BT in treating stroke due to carotid T occlusion in favorable outcome, successful recanalization, 90-day morality and sICH. However, BT may increase the incidence of ICH in this specific type stroke.

High Dietary Inflammatory Index Is Associated With Increased Plaque Vulnerability of Carotid in Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: Long-term dietary patterns can influence the intensity of systemic inflammation and, therefore, the development of atherosclerosis. This study aimed to evaluate the association between dietary inflammatory index (DII) and vulnerability characteristics of carotid atherosclerotic plaques in patients with ischemic stroke. METHODS: Patients with ischemic stroke within 7 days of onset were enrolled. DII was calculated from 32 food components with the help of a food frequency questionnaire. Vulnerable plaque was defined as presence of artery positive remodeling (remodeling index >1.1) and low CT attenuation plaques (<35 HU) on carotid arteries by computed tomography angiography. RESULTS: Of the 398 enrolled patients, 144 (36.2%) were detected with vulnerable plaque. Their DII ranged from -4.58 to 4.18. Patients with vulnerable plaques consumed less nutrients with anti-inflammatory properties, less fruits and vegetables (85.6±64.3 versus 94.6±74.4 g/d, P=0.027), and less nuts (5.66±7.14 versus 8.84±15.9 g/d, P=0.024) than patients without vulnerable plaques. Patients with vulnerable plaque had higher DII than patients without vulnerable plaque (-0.26±1.54 versus -0.64±1.53, P=0.018). Logistic regression analysis revealed that DII was associated with vulnerable plaques after adjusted for major confounding factors (odds ratio=1.307; 95% CI, 1.113-1.533). CONCLUSIONS: DII is associated with the vulnerability of carotid plaques in patients with ischemic stroke. Considering a possible causal relationship, the mechanisms underlying the association between diet and atherosclerosis warrant further study.

A Nomogram for Predicting Stroke Recurrence Among Young Adults.

Background and Purpose- This study aimed to develop and validate a nomogram for predicting the risk of stroke recurrence among young adults after ischemic stroke. Methods- Patients aged between 18 and 49 years with first-ever ischemic stroke were selected from the Nanjing Stroke Registry Program. A stepwise Cox proportional hazards regression model was employed to develop the best-fit nomogram. The discrimination and calibration in the training and validation cohorts were used to evaluate the nomogram. All patients were classified into low-, intermediate-, and high-risk groups based on the risk scores generated from the nomogram. Results- A total of 604 patients were enrolled in this study. Hypertension (hazard ratio [HR], 2.038 [95% CI, 1.504-3.942]; P=0.034), diabetes mellitus (HR, 3.224 [95% CI, 1.848-5.624]; P<0.001), smoking status (current smokers versus nonsmokers; HR, 2.491 [95% CI, 1.304-4.759]; P=0.006), and stroke cause (small-vessel occlusion versus large-artery atherosclerosis; HR, 0.325 [95% CI, 0.109-0.976]; P=0.045) were associated with recurrent stroke. Educational years (>12 versus 0-6; HR, 0.070 [95% CI, 0.015-0.319]; P=0.001) were inversely correlated with recurrent stroke. The nomogram was composed of these factors, and successfully stratified patients into low-, intermediate-, and high-risk groups (P<0.001). Conclusions- The nomogram composed of hypertension, diabetes mellitus, smoking status, stroke cause, and education years may predict the risk of stroke recurrence among young adults after ischemic stroke.

Symptomatic Intracranial Hemorrhage After Mechanical Thrombectomy in Chinese Ischemic Stroke Patients: The ASIAN Score.

BACKGROUND AND PURPOSE: Symptomatic intracranial hemorrhage (sICH), potentially associated with poor prognosis, is a major complication of endovascular thrombectomy (EVT) for ischemic stroke patients. We aimed to develop and validate a risk model for predicting sICH after EVT in Chinese patients due to large-artery occlusions in the anterior circulation. METHODS: The derivation cohort recruited patients with EVT from the Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke Registry in China. sICH was diagnosed according to the Heidelberg Bleeding Classification within 24 hours of EVT. Stepwise logistic regression was performed to derive the predictive model. The discrimination and calibration of the risk model were assessed using the C index and the calibration plot. An additional cohort of 503 patients from 2 stroke centers was prospectively enrolled to validate the new model. RESULTS: We enrolled 629 patients who underwent EVT as the derivation cohort, among whom 87 developed sICH (13.8%). In the multivariate adjustment, Alberta Stroke Program Early CT Score (odds ratio [OR], 0.85; P=0.005), baseline glucose (OR, 1.13; P=0.001), poor collateral circulation (OR, 3.06; P=0.001), passes with retriever (OR, 1.52; P=0.001), and onset-to-groin puncture time (OR, 1.79; P=0.024) were independent factors of sICH and were incorporated as the Alberta Stroke Program Early CT Score, Baseline Glucose, Poor Collateral Circulation, Passes With Retriever, and Onset-to-Groin Puncture Time (ASIAN) score. The ASIAN score demonstrated good discrimination in the derivation cohort (C index, 0.771 [95% CI, 0.716-0.826]), as well as the validation cohort (C index, 0.758 [95% CI, 0.691-0.825]). CONCLUSIONS: The ASIAN score reliably predicts the risk of sICH in Chinese ischemic stroke patients treated by EVT.

High-frequency repetitive transcranial magnetic stimulation improves functional recovery by inhibiting neurotoxic polarization of astrocytes in ischemic rats.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment for ischemic stroke. Astrocytes regulation has been suggested as one mechanism for rTMS effectiveness. But how rTMS regulates astrocytes remains largely undetermined. There were neurotoxic and neuroprotective phenotypes of astrocytes (also denoted as classically and alternatively activated astrocytes or A1 and A2 astrocytes) pertaining to pro- or anti-inflammatory gene expression. Pro-inflammatory or neurotoxic polarized astrocytes were induced during cerebral ischemic stroke. The present study aimed to investigate the effects of rTMS on astrocytic polarization during cerebral ischemic/reperfusion injury. METHODS: Three rTMS protocols were applied to primary astrocytes under normal and oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Cell survival, proliferation, and phenotypic changes were assessed after 2-day treatment. Astrocytes culture medium (ACM) from control, OGD/R, and OGD/R + rTMS groups were mixed with neuronal medium to culture neurons for 48 h and 7 days, in order to explore the influence on neuronal survival and synaptic plasticity. In vivo, rats were subjected to middle cerebral artery occlusion (MCAO), and received posterior orbital intravenous injection of ACM collected from different groups at reperfusion, and at 3 days post reperfusion. The apoptosis in the ischemic penumbra, infarct volumes, and the modified Neurological Severity Score (mNSS) were evaluated at 1 week after reperfusion, and cognitive functions were evaluated using the Morris Water Maze (MWM) tests. Finally, the 10 Hz rTMS was directly applied to MCAO rats to verify the rTMS effects on astrocytic polarization. RESULTS: Among these three frequencies, the 10 Hz protocol exerted the greatest potential to modulate astrocytic polarization after OGD/R injury. Classically activated and A1 markers were significantly inhibited by rTMS treatment. In OGD/R model, the concentration of pro-inflammatory mediator TNF-α decreased from 57.7 to 23.0 Ñ€g/mL, while anti-inflammatory mediator IL-10 increased from 99.0 to 555.1 Ñ€g/mL in the ACM after rTMS treatment. The ACM collected from rTMS-treated astrocytes significantly alleviated neuronal apoptosis induced by OGD/R injury, and promoted neuronal plasticity. In MCAO rat model, the ACM collected from rTMS treatment decreased neuronal apoptosis and infarct volumes, and improved cognitive functions. The neurotoxic astrocytes were simultaneously inhibited after rTMS treatment. CONCLUSION: Inhibition of neurotoxic astrocytic polarization is a potential mechanism for the effectiveness of high-frequency rTMS in cerebral ischemic stroke.

Lipocalin-2 may produce damaging effect after cerebral ischemia by inducing astrocytes classical activation.

BACKGROUND: Functions of astrocytes in the rehabilitation after ischemic stroke, especially their impacts on inflammatory processes, remain controversial. This study uncovered two phenotypes of astrocytes, of which one was helpful, and the other harmful to anoxic neurons after brain ischemia. METHODS: We tested the levels of inflammatory factors including TNF-a, IL-6, IL-10, iNOS, IL-1beta, and CXCL10 in primary astrocytes at 0 h, 6 h, 12 h, 24 h, and 48 h after OGD, grouped the hypoxia astrocytes into iNOS-positive (iNOS(+)) and iNOS-negative (iNOS(-)) by magnetic bead sorting, and then co-cultured the two groups of cells with OGD-treated neurons for 24 h. We further verified the polarization of astrocytes in vivo by detecting the co-localization of iNOS, GFAP, and Iba-1 on MCAO brain sections. Lentivirus overexpressing LCN2 and LCN2 knockout mice (#024630. JAX, USA) were used to explore the role of LCN2 in the functional polarization of astrocytes. 7.0-T MRI scanning and the modified Neurological Severity Score (mNSS) were used to evaluate the neurological outcomes of the mice. RESULTS: After oxygen-glucose deprivation (OGD), iNOS mRNA expression increased to the peak at 6 h in primary astrocytes, but keep baseline expression in LCN2-knockout astrocytes. In mice with transient middle cerebral artery occlusion (tMCAO), LCN2 was proved necessary for astrocyte classical activation. In LCN2 knockout mice with MCAO, no classically activated astrocytes were detected, and smaller infarct volumes and better neurological functions were observed. CONCLUSIONS: The results indicated a novel pattern of astrocyte activation after ischemic stroke and lipocalin-2 (LCN2) plays a key role in polarizing and activating astrocytes.

Socioeconomic Status and the Risk of Stroke Recurrence in Chinese Patients.

BACKGROUND: The association between socioeconomic status (SES) and the risk of stroke recurrence has been rarely studied, especially in a developing country. OBJECTIVE: This study aimed to evaluate the association between SES and the risk of stroke recurrence in Chinese stroke patients. METHODS: Patients with first-ever ischemic stroke registered in the Nanjing Stroke Registry Program from 2013 to 2015 were enrolled and followed in this study. Information about SES, measured by disposable income and educational level, was collected at baseline. The primary endpoint was defined as fatal or nonfatal recurrent stroke after 7 days of the index stroke. The association between SES and the risk of stroke recurrence was analyzed with multivariate Cox regression model. RESULTS: A total of 2,294 patients with first-ever stroke were included in the study. During a mean follow-up of 2.8 ± 1.2 years, 298 (13.0%) patients had stroke recurrence. After adjusting for potential confounding factors, compared with patients with a monthly family income of USD ≥1,539, those with an income of USD 769-1,538, USD 462-768, and USD 1-461 had an adjusted hazard ratio (HR) of 1.87 (95% CI 1.11-3.17), 2.40 (95% CI 1.43-4.03), and 2.79 (95% CI 1.65-4.69) for recurrence, respectively. Compared with those with an educational level of ≥13 years, patients with an educational level of 7-12 years and 0-6 years had adjusted HRs of 1.21 (95% CI 0.79-1.86) and 1.73 (95% CI 1.11-2.70), respectively. CONCLUSIONS: Chinese stroke patients with lower SES bear higher recurrent risk. These results are suggestive for secondary stroke prevention in Chinese patients.

Safety of Intra-Arterial Tirofiban Administration in Ischemic Stroke Patients after Unsuccessful Mechanical Thrombectomy.

PURPOSE: To assess the safety of low-dose intra-arterial (IA) tirofiban bolus after unsuccessful mechanical thrombectomy in patients with ischemic stroke due to large artery occlusion in anterior cerebral circulation. MATERIALS AND METHODS: Patients with ischemic stroke who were treated with mechanical thrombectomy were enrolled in a multicenter registry. Low-dose tirofiban was injected into the residual arterial thrombus in patients after unsuccessful mechanical thrombectomy. The major safety measurement was defined as symptomatic intracranial hemorrhage (SICH). The functional outcome at 90 days was assessed with the modified Rankin Scale, and a score of 0-2 was defined as favorable. RESULTS: Of the 632 enrolled patients, 154 (24.4%) received IA tirofiban treatment. The SICH rate was 13.6% (21/154) in patients with tirofiban and 16.7% (80/478) in patients without tirofiban (P = .361). IA tirofiban was not associated with increased risk of SICH (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.36-1.31; P = .26). IA tirofiban treatment did not increase the risk of mortality at 90 days of the index stroke (OR, 0.66; 95% CI, 0.36-1.31; P = .15). Patients with large artery atherosclerosis stroke who were treated with tirofiban were associated with decreased risk of death (OR, 11.3% vs 23.4%; P = .042) compared to patients who were not treated with tirofiban. CONCLUSIONS: Low-dose IA tirofiban administration may be relatively safe in patients with ischemic stroke after unsuccessful recanalization.

Recurrent risk of ischemic stroke due to Vertebrobasilar Dolichoectasia.

BACKGROUND: Patients with vertebrobasilar dolichoectasia usually have persistent hemodynamic abnormalities, and therefore, may bear an increased risk of stroke. This study aimed to identify risk factors for stroke recurrence in patients with vertebrobasilar dolichoectasia. METHODS: Patients with acute ischemic stroke were screened and evaluated for eligibility. Enrolled patients were followed via scheduled clinical visits or telephone interviews. Ischemic stroke recurrence was proposed with clinical symptoms and confirmed with cranial Magnetic Resonance Imaging or Computerized Tomography scans. Baseline characteristics and vascular geometry were compared between patients with and without stroke recurrence. Significant parameters were introduced into COX proportional hazard model to detect possible predictors of stroke recurrence. RESULTS: A total of 115 stroke patients with vertebrobasilar dolichoectasia were enrolled, of which 22 (19.1%) had recurrence during 22 ± 6 months follow-up. Basilar artery diameter ≥ 5.3 mm (HR = 4.744; 95% CI, 1.718-13.097; P = 0.003), diffuse intracranial dolichoectasia (HR = 3.603; 95% CI, 1.367-9.496; P = 0.010) and ischemic heart disease history (HR = 4.095; 95% CI, 1.221-13.740; P = 0.022) had increased risk of recurrence. CONCLUSIONS: Stroke patients with vertebrobasilar dolichoectasia may have a high risk of recurrence. Larger basilar artery diameter or diffuse intracranial dolichoectasia may increase the risk of recurrence.

Carotid Geometry as a Predictor of In-Stent Neointimal Hyperplasia　- A Computational Fluid Dynamics Study.

BACKGROUND: Carotid angioplasty and stenting (CAS) is emerging as an alternative treatment for carotid stenosis, but neointimal hyperplasia (NIH) remains a drawback of this treatment strategy. This study aimed to evaluate the effect of variations of carotid bifurcation geometry on local hemodynamics and NIH.Methods and Results:Hemodynamic and geometric effects on NIH were compared between 2 groups, by performing computational fluid dynamics (CFD) simulations both on synthetic models and patient-specific models. In the idealized models, multiple regression analysis revealed a significant negative relationship between internal carotid artery (ICA) angle and the local hemodynamics. In the patient-derived models, which were reconstructed from digital subtraction angiography (DSA) of 25 patients with bilateral CAS, a low time-average wall shear stress (TAWSS) and a high oscillatory shear index (OSI) were often found at the location of NIH. Larger difference values of the OSI percentage area (10.56±20.798% vs. -5.87±18.259%, P=0.048) and ECA/CCA diameter ratio (5.64±12.751% vs. -3.59±8.697%, P=0.047) were detected in the NIH-asymmetric group than in the NIH-symmetric group. CONCLUSIONS: Changes in carotid bifurcation geometry can make apparent differences in hemodynamic distribution and lead to bilateral NIH asymmetry. It may therefore be reasonable to consider certain geometric variations as potential local risk factors for NIH.