The functions of exosomes targeting astrocytes and astrocyte-derived exosomes targeting other cell types.

Astrocytes are the most abundant glial cells in the central nervous system; they participate in crucial biological processes, maintain brain structure, and regulate nervous system function. Exosomes are cell-derived extracellular vesicles containing various bioactive molecules including proteins, peptides, nucleotides, and lipids secreted from their cellular sources. Increasing evidence shows that exosomes participate in a communication network in the nervous system, in which astrocyte-derived exosomes play important roles. In this review, we have summarized the effects of exosomes targeting astrocytes and the astrocyte-derived exosomes targeting other cell types in the central nervous system. We also discuss the potential research directions of the exosome-based communication network in the nervous system. The exosome-based intercellular communication focused on astrocytes is of great significance to the biological and/or pathological processes in different conditions in the brain. New strategies may be developed for the diagnosis and treatment of neurological disorders by focusing on astrocytes as the central cells and utilizing exosomes as communication mediators.

Antioxidants and the risk of stroke: results from NHANES and two-sample Mendelian randomization study.

BACKGROUND: Stroke is the second leading cause of death worldwide, and observational studies have suggested a correlation between antioxidants and reduced stroke risk. However, it remains unclear whether causal relationships exist. METHODS: This study first performed a cross-sectional study of the association between the Composite Dietary Antioxidant Index (CDAI) and stroke using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Second, a two-sample univariable Mendelian Randomization (MR) was performed to analyze the causal effect of circulating levels of antioxidants on different subtypes of stroke. RESULTS: The cross-sectional study included a total of 24,892 participants representing more than 200 million US non-institutionalized residents, a multivariable logistic regression model revealed that the risk of stroke decreased by 3.4% for each unit increase in CDAI (P = 0.017), with a non-linear association found, indicating a reduction in stroke risk before an inflection point of 3.078. MR analysis revealed that genetically determined levels of retinol had a suggestive protective effect on subarachnoid hemorrhage (SAH) (OR = 0.348, P = 0.025), and genetically determined levels of selenium had a suggestive protective effect against SAH (OR = 0.826, P = 0.007). However, no causal relationship was found between antioxidants and ischemic stroke or intracranial hemorrhage risk. CONCLUSIONS: Evidence suggests that diet-derived antioxidants may reduce the risk of stroke, as indicated by the protective effects of retinol and selenium against SAH. However, more research is needed to fully understand how antioxidants prevent stroke.

Reperfusion status and postoperative blood pressure in acute stroke patients after endovascular treatment.

Background and purpose: An aggressive lowering of blood pressure (BP) could lead to neurological worsening, particularly of the area that has not been reperfused in acute stroke patients with large vessel occlusion (LVO). We sought to investigate the association of reperfusion status and BP course following mechanical thrombectomy (MT) with outcomes in LVO. Materials and methods: Consecutive patients with LVO treated with MT between Jan 2020 to Jun 2021 were enrolled in a retrospective cohort study. Hourly systolic BP (SBP) and diastolic BP (DBP) were recorded for 72 h following MT and maximum SBP and DBP levels were identified. The Extended Thrombolysis in Cerebral Infarction (eTICI) scale was used to assess reperfusion extent. LVO patients were stratified in 2 groups based on reperfusion status: complete reperfusion (eTICI 3) and incomplete reperfusion (eTICI 2b/c). Three-month functional independence was defined as a modified Rankin Scale score of 0-2. Results: A total of 263 acute ischemic stroke patients with LVO were retrospectively evaluated. Complete reperfusion was achieved in 210 patients (79.8%). Post-MT maximum SBP over 160 mmHg was significantly related to worse functional outcome (38.1% vs. 55.7%, p = 0.006), higher likelihood of in-hospital mortality and 3-month mortality (19.0% vs. 6.9%, p = 0.004, 27.4% vs. 14.3%, p = 0.012). No statistical correlation was found between reperfusion status and blood pressure level (p > 0.05). In patients with complete reperfusion, patients with an average BP 120-140 mmHg tends to have worse functional outcome compared with 100-120 mmHg (OR = 1.77, 95%CI: 0.97-3.23, p = 0.061). Conclusion: High maximum SBP levels following MT are associated with an increased likelihood of 3-month functional dependence and mortality. An average BP of 100-120 mmHg tends to have better functional independence in completely reperfused patients. The effect of intensive BP control on incomplete reperfusion still warrants further investigations.

Association between blood pressure and different antihypertensive drugs with outcome after ischemic stroke: A Mendelian randomization study.

BACKGROUND: Observational studies suggest an association between blood pressure (BP) and functional outcomes in ischemic stroke patients but whether this is causal or due to confounding is uncertain. We used Mendelian randomization (MR) to assess causality, and also explore whether particular classes of anti-hypertensives were associated with a better outcome after ischemic stroke. METHODS: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3-month dependence or death defined as a modified Rankin Scale (mRS) of 3-6. The secondary outcome was disability or death after 90 days defined as mRS 2-6. Cochran's Q statistic in the inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-single-nucleotide polymorphism (SNP)-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses. RESULTS: Genetic predisposition to higher systolic and diastolic BP was associated with disability or death after ischemic stroke in univariable IVW MR analysis (odds ratio (OR) 1.29, 95% confidence interval (CI): 1.05-1.59, p = 0.014; OR 1.27, 95% CI: 1.07-1.51, p = 0.006, respectively). Pulse pressure was associated with both dependence or death and disability or death after ischemic stroke (OR = 1.05, 95% CI: 1.02-1.08, p = 0.002; OR = 1.04, 95% CI = 1.01-1.07, p = 0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB) were significantly associated with improved functional outcomes (dependence or death, OR 0.76, 95% CI: 0.62-0.94, p = 0.009; OR 0.89, 95% CI: 0.83-0.97, p = 0.005). Proxies for ß-blockers, angiotensin receptor blockers (ARB), and thiazides failed to show associations with functional outcomes (p > 0.05). CONCLUSION: We provide evidence for an association of genetic predisposition to higher BP with a higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcomes in ischemic stroke.

Trend of research on the medical use of molecular hydrogen: a bibliometric analysis.

The medical use of molecular hydrogen, including hydrogen-rich water and hydrogen gas, has been extensively explored since 2007. This article aimed to demonstrate the trend in medical research on molecular hydrogen. A total of 1126 publications on hydrogen therapy were retrieved from the PubMed database until July 30, 2021. From 2007 to 2020, the number of publications in this field had been on an upward trend. Medical Gas Research, Scientific Report and Shock have contributed the largest number of publications on this topic. Researchers by the name of Xue-Jun Sun, Ke-Liang Xie and Yong-Hao Yu published the most studies in the field. Analysis of the co-occurrence of key words indicated that the key words "molecular hydrogen," "hydrogen-rich water," "oxidative stress," "hydrogen gas," and "inflammation" occurred most frequently in these articles. "Gut microbiota," "pyroptosis," and "COVID-19" occurred the most recently among the keywords. In summary, the therapeutic application of molecular hydrogen had attracted much attention in these years. The advance in this field could be caught up by subscribing to relevant journals or following experienced scholars. Oxidative stress and inflammation were the most important research directions currently, and gut microbiota, pyroptosis, and coronavirus disease 2019 might become hotspots in the future.

Cost-effectiveness of thrombectomy alone versus alteplase before thrombectomy in acute ischemic stroke: results from the DIRECT-MT.

OBJECTIVE: The use of thrombectomy alone (endovascular thrombectomy [EVT]) was found to be noninferior to combination therapy (EVT plus intravenous thrombolysis [IVT] with alteplase before thrombectomy [EVT+IVT]) in the DIRECT-MT (Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: A Multicenter Randomized Clinical Trial), yet the economic value of omitting alteplase was unclear. Thus, in this paper the authors assessed the cost-effectiveness of EVT alone versus EVT+IVT in the DIRECT-MT. METHODS: In the context of the Chinese healthcare system, the authors conducted a post hoc economic analysis of the DIRECT-MT based on an intention-to-treat approach. Index stroke costs were collected at the individual level, while costs after discharge were complemented with published literature and government websites. Utility weights assessed at 90 days using the 5-Level EQ-5D questionnaire were prospectively collected. For long-term modeled cost-effectiveness analysis, a Markov model with 7 health states corresponding to the 7 modified Rankin Scale scores was used. Deterministic and probabilistic sensitivity analyses were performed. All costs are expressed in 2019 US dollars, discounted using the annual Consumer Price Index in China. RESULTS: During the index hospitalization, the mean medication cost in the EVT-alone group was $487 lower than that in the EVT+IVT group ($2453 [95% CI $2205-$2701] vs $2940 [95% CI $2703-$3178], p = 0.01), but the mean overall costs were similar between the groups ($15,565 [95% CI $14,876-$16,254] vs $15,472 [95% CI $14,714-$16,230], p = 0.73). Within 90 days of the trial, there were no significant differences in total costs (difference -$222 [95% CI -$603 to $161], p = 0.06, bootstrapping) or utility values (median 0.84 [IQR 0.48-0.95] vs median 0.85 [IQR 0.26-1.00]; beta coefficient < 0.01 [95% CI -0.06 to 0.07]) between EVT alone and EVT+IVT. Over the lifetime horizon, EVT alone and EVT+IVT yielded comparable lifetime QALYs (2.02 QALYs [95% CI -0.07 to 4.55 QALYs] vs 1.90 QALYs [95% CI -0.09 to 4.55 QALYs]) and costs ($26,795 [95% CI $15,281-$54,463] vs $27,632 [95% CI $14,558-$52,251]). CONCLUSIONS: In this economic analysis based on a trial conducted in China, the authors found that EVT alone was not associated with economic dominance over EVT+IVT in patients with anterior circulation large-vessel occlusion.

Novel predictors and a predictive model of cerebrovascular atherosclerotic ischemic stroke based on clinical databases.

BACKGROUND AND PURPOSE: Early identification of cerebrovascular atherosclerotic ischemic stroke is necessary for accurate treatment and clinical research. AIMS: To identify novel predictors and build a predictive model of ischemic strokes due to cerebrovascular atherosclerosis. METHOD: MIMIC-IV database was used to search for clinical data of patients with ischemic stroke. Included patients were divided into two groups according to their etiologies. Univariate and multivariate logistic regressions were used to build the predictive model, and the model reliability parameters were calculated. The cut-off value for the model was selected according to the Youden index. Clinical data from the Neurovascular Center of Changhai Hospital were used to verify the predictive model. RESULTS: Logistical regressions showed a positive correlation between advanced age, peripheral atherosclerosis, history of transient ischemia, and the diagnosis of ischemic strokes due to cerebrovascular atherosclerosis. The history of atrial fibrillation, levels of the National Institutes of Health Stroke Scale, serum potassium, and activated partial thromboplastin time were negatively correlated to the diagnosis of cerebrovascular atherosclerotic ischemic stroke. The predictive model was constructed from logistic regression results, and the area under the curve was 0.764. The cut-off value for the model was set at 0.089 to achieve the highest Youden index, with sensitivity and specificity of 75.9% and 64.1%. Clinical verification of the model revealed that the sensitivity and specificity of the model were 52.5% and 93.0% respectively. CONCLUSION: The efficacy of the predictive model was acceptable as an aid in predicting cerebrovascular atherosclerotic ischemic stroke.

Preliminary experience with recanalization of large vessel occlusion due to underlying long-segment dissection using a standby microwire technique.

Purpose: This study aimed at investigating a novel standby microwire technique to facilitate revascularization of large vessel occlusion due to underlying long-segment dissection. Methods: Patients with acute ischemic stroke with emergent large vessel occlusion (ELVO) due to underlying long-segment dissection were screened from the prospectively established database between January 2021 and May 2022. The clinical and radiological data of eligible patients who underwent endovascular treatment by using a standby microwire technique were investigated. Results: Of the 165 acute ischemic stroke patients who underwent mechanical thrombectomy, the standby microwire technique was used in five patients aged 33-55 years old with occlusion due to underlying long-segment dissection. Of them, three patients were diagnosed with tandem lesions and three were located at the anterior circulation. A 300 cm exchange microwire was used as the standby microwire. Stent deployment was performed in all five patients. Groin puncture to reperfusion time ranged from 10-68 min. Technical success and favorable clinical outcomes were achieved in all five patients (100%). No technique-related complication was observed. Conclusion: Our preliminary experience showed that the standby microwire technique was a useful ancillary approach to facilitate the revascularization of large vessel occlusion due to underlying long-segment dissection.

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. METHODS: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140-180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. FINDINGS: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07-1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18-1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47-2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. INTERPRETATION: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. FUNDING: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.

Case Report: Fenestration embedded in large vessel occlusion at non-branching site: A catastrophic trap for mechanical thrombectomy.

Fenestrations are rare anatomical variants characterized by division of an artery into two channels which join distally to form a single lumen. We here present two acute ischemic stroke patients with occlusion in an arterial segment with fenestration. Both occlusion sites were located at the non-branching site: one in the mid-basilar trunk and one middle cerebral artery trunk. Successful reperfusion was achieved in both patients, but angioplasty was avoided during thrombectomy procedure. The two cases establish that fenestration may be embedded in non-branching site occlusion. Surgeons should take this abnormality into account to prevent angioplasty from causing vessel rupture in the setting of fenestration.

Single-Cell RNA-Sequencing Analyses Revealed Heterogeneity and Dynamic Changes of Metabolic Pathways in Astrocytes at the Acute Phase of Ischemic Stroke.

Astrocyte plays important roles in the pathogenesis of ischemic stroke and reperfusion injury. They intensively participate in the energy metabolism of the brain, while their heterogeneity and function after ischemic stroke remain controversial. By employing single-cell sequencing of mice cortex at 12 h after transient middle cerebral artery occlusion (tMCAO) and comparing with the similar published datasets of 24h after tMCAO, we uncover the cellular phenotypes and dynamic change of astrocytes at the acute phase of ischemic stroke. In this study, we separately identified 3 major subtypes of astrocytes at the 12 h-tMCAO-system and 24 h-tMCAO-system, indicated the significant differences in the expression of genes and metabolic pathways in the astrocytes between the two time nodes after ischemic stroke, and detected the major change in the energy metabolism. These results provided a comprehensive understanding of the characteristic changes of astrocytes after ischemic stroke and explored the potential astrocytic targets for neuroprotection.

AKG Attenuates Cerebral Ischemia-Reperfusion Injury through c-Fos/IL-10/Stat3 Signaling Pathway.

Inflammation is dominant in the pathogenesis of ischemic stroke (IS). Alpha-ketoglutarate (AKG), according to previous studies, has demonstrated a variety of pharmacological effects such as antioxidation and inhibitive inflammation activities. However, whether AKG ameliorates cerebral ischemic injury, as well as the underlying molecular events, is still unclear. Therefore, the effect and underlying mechanisms of AKG on ischemic brain injury should be identified. The study established a cerebral ischemia-reperfusion (I/R) model in mice as well as an oxygen-glucose deprivation/reperfusion (OGD/R) model in SH-SY5Y cells, respectively. It was observed that AKG markedly suppressed infarction volume and neuronal injuries and improved the neurological score in vivo. Moreover, AKG reduced the inflammatory response and lowered the expression of proinflammatory cytokines. In vitro, AKG treatment strongly inhibited OGD/R-induced neuronal injury and the proinflammatory factors. It was also found that the increased SOD and GSH levels, as well as the lower ROS levels, showed that AKG reduced oxidative stress in OGD/R-treated SY-SY5Y cells. Mechanistically, AKG largely promoted IL-10 expression in ischemic brain injury and OGD/R-induced neuronal injury. Furthermore, IL-10 silencing neutralized the protective effect of AKG on inflammation. Notably, it was discovered that AKG could upregulate IL-10 expression by promoting the translocation of c-Fos from the cytoplasm to the nucleus. The results indicated that AKG demonstrated neuroprotection on cerebral ischemia while inhibiting inflammation through c-Fos/IL-10/stat3 pathway.

The 8-year single-center experience of telescoping flow diverter for complex intracranial aneurysms treatment.

OBJECTIVE: Treatment of complex intracranial aneurysms (IAs) is still a challenging thing and this study aims to summarize the experience of telescoping flow diverters (FDs) in treating complex intracranial aneurysms. METHOD: Between April 2013 to November 2020, 381 IA cases treated by flow diverters (FD) were retrieved from the database of 4988 IA cases, and finally 20 cases treated by telescoping FDs were enrolled for further analysis. RESULT: Among 20 patients, 15 patients (75.0%) received Tubridge telescoping while 5 patients (25.0%) received PED telescoping. The technical success rate was 100%. The immediate occlusion results were: 7 cases of OKM grade A (35.0%), 11 cases of OKM grade B (55.0%), and 2 cases of OKM grade C (10.0%). No perioperative complications occurred. The clinical follow-up was available in 20 patients (100%) and the follow-up time was 6-96 months. One patient developed massive infarction and the other 19 patients were range between 0 and 2. The angiographic follow-up was available in 17 patients (85%) and the follow-up time was 6-27 months. The occlusion results were: 1 case of OKM grade B (5.9%), 6 cases of OKM grade C (35, 0.3%), and 10 cases of OKM grade D (58.8%). 2 patients (11.8%) developed occlusion of the patent artery. CONCLUSION: Telescoping flow diverters showed low perioperative complications and high IA occlusion rate when treating complex intracranial aneurysms in follow-up time, which provides an alternative manner beyond conventional strategy for neurosurgeons.

Endovascular Treatment for Acute Basilar Artery Occlusion: A Comparison of Arteriosclerotic, Embolic and Tandem Lesions.

PURPOSE: To evaluate the safety and efficacy of endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to intracranial atherosclerosis-related basilar artery occlusion (ICAS-related BAO) by comparison with embolic and tandem occlusion. METHODS: We retrospectively reviewed consecutive patients with AIS due to BAO who underwent EVT. Patients were assigned to the ICAS-related group and embolic group, and tandem group based on the etiology. Baseline data, procedural details, and clinical outcomes were compared between the three groups. RESULTS: A total of 100 patients (ICAS-related group: 31; embolic group: 41; tandem group: 28) were included. No significant difference was observed in the successful reperfusion (mTICI 2b or 3), but the procedural time differed significantly (60 min vs. 43 min vs. 60 min, P = 0.010). There were no differences in the different intracranial hemorrhage grades among the three groups (P = 0.134). After adjusting for baseline differences, there was no significant difference in pairwise comparisons regarding favorable outcome (mRS 0-2), moderate outcome (mRS 0-3), and mortality. CONCLUSIONS: Endovascular treatment for patients with acute ICAS-related BAO had equal efficacy and safety compared with embolic BAO and tandem BAO. Primary endovascular treatment and rescue modalities were effective treatments for acute ICAS-related BAO.

Efficacy and Safety of a Novel Thrombectomy Device in Patients With Acute Ischemic Stroke: A Randomized Controlled Trial.

Purpose: The Tonbridge stent is a novel retriever with several design improvements which aim to achieve promising flow reperfusion in the treatment of acute ischemic stroke (AIS). We conducted a randomized controlled, multicenter, non-inferiority trial to compare the safety and efficacy of the Tonbridge stent with the Solitaire FR. Methods: AIS patients aged 18-85 years with large vessel occlusion in anterior circulation who could undergo puncture within 6 h of symptom onset were included. Randomization was performed on a 1:1 ratio to thrombectomy with either the Tonbridge stent or the Solitaire FR. The primary efficacy endpoint was successful reperfusion using a modified thrombolysis in cerebral infarction score (mTICI) of 2b/3. Safety outcomes were symptomatic intracranial hemorrhage (sICH) within 24 ± 6 h and all-cause mortality within 90 days. A clinically relevant non-inferiority margin of 12% was chosen as the acceptable difference between groups. Secondary endpoints included time from groin puncture to reperfusion, National Institutes of Health Stroke Scale (NIHSS) score at 24 h and at 7 days, and a modified Rankin Scale (mRS) score of 0-2 at 90 days. Results: A total of 220 patients were enrolled; 104 patients underwent thrombectomy with the Tonbridge stent and 104 were treated with the Solitaire FR. In all test group patients, the Tonbridge was used as a single retriever without rescuing by other thrombectomy devices. Angioplasty with balloon and/or stent was performed in 26 patients in the Tonbridge group and 16 patients in the Solitaire group (p = 0.084). Before angioplasty, 86.5% of those in the Tonbridge group and 81.7% of those in the Solitaire group reached successful reperfusion (p = 0.343). Finally, more patients in the Tonbridge group achieved successful reperfusion (92.3 vs. 84.6%, 95% CI of difference value 0.9-16.7%, p < 0.0001). There were no significant differences on sICH within 24 ± 6 h between the two groups. All-cause mortality within 90 days was 13.5% in the Tonbridge group and 16.3% in the Solitaire group (p = 0.559). We noted no significant differences between groups on the NIHSS at either 24 h or 7 days and the mRS of 0-2 at 90 days. Conclusion: The trial indicated that the Tonbridge stent was non-inferior to the Solitaire FR within 6 h of symptom onset in cases of large vessel occlusion stroke. Clinical Trial Registration:ClinicalTrials.gov, number: NCT03210623.

Exosomes containing miR-451a is involved in the protective effect of cerebral ischemic preconditioning against cerebral ischemia and reperfusion injury.

AIM: To study the role of exosomes in the protective effect of cerebral ischemic preconditioning (cerebral-IPC) against cerebral I/R injury. METHOD: Mouse models of cerebral-IPC and MCAO/R were established as described previously, and their behavioral, pathological, and proteomic changes were analyzed. Neuro-2a subjected to OGD/R were treated with exosomes isolated from the plasma of sham-operated and cerebral-IPC mice. The differentially expressed miRNAs between exosomes derived from sham-operated (S-exosomes) and preconditioned (IPC-exosomes) mice were identified through miRNA array, and their targets were identified through database search. The control and OGD/R cells were treated with the IPC-exosomes, miRNA mimic or target protein inhibitor, and their viability, oxidative, stress and apoptosis rates were measured. The activated pathways were identified by analyzing the levels of relevant proteins. RESULTS: Cerebral-IPC mitigated the cerebral injury following ischemia and reperfusion, and increased the number of plasma exosomes. IPC-exosomes increased the survival of Neuro-2a cells after OGD/R. The miR-451a targeting Rac1 was upregulated in the IPC-exosomes relative to S-exosomes. The miR-451a mimic and the Rac1 inhibitor NSC23766 reversed OGD/R-mediated activation of Rac1 and its downstream pathways. CONCLUSION: Cerebral-IPC ameliorated cerebral I/R injury by inducing the release of exosomes containing miR-451a.

Rescue permanent LVIS stenting with post-stenting angioplasty after failed mechanical thrombectomy for refractory internal carotid artery occlusion at the paraclinoid segment: two-case report.

BACKGROUND: Previous studies indicated the effectiveness of permanent stenting when dealing with retriever-failed refractory large vascular occlusion (LVO). Variety types of stents were implanted permanently to achieve recanalization. Low-profile visualized intraluminal support (LVIS) is generally used as a supportive device for embolization of intracranial aneurysm. Its specific structural and functional characteristics contribute to its potential of treating LVO. CASES PRESENTATION: A 51-year-old male was transferred to our stroke center because of conscious disturbance with the weakness of the left upper limb. The National Institute of Health Stroke Scale (NIHSS) was 24; the Glasgow Coma Scale (GCS) was 10. Digital subtraction angiography (DSA) showed that his paraclinoid segment of R-ICA was occluded due to hard clot embolization. Thrombectomy was performed 6 times, but the occlusion remained. Finally, LVIS was implanted permanently and post-dilation was performed, which successfully recanalized the artery (eTICI 2c). The post-operative NIHSS and GCS were 20 and 11, respectively, which were 10 and 14 when discharged. Another patient was a 71-year-old male who suffered weakness of left limbs. NIHSS was 15; GCS was 11. DSA confirmed that the paraclinoid segment of his R-ICA was occluded due to hard clot embolization. Totally 6 times of mechanical thrombectomy, angioplasty, and tirofiban infusion were performed, which failed to recanalize the artery. In the end, LVIS implantation with post-dilation was performed, and full recanalization was achieved (mTICI 3). The post-operative NIHSS and GCS were 9 and 15, respectively, which were 3 and 15 when discharged. CONCLUSIONS: These 2 cases invited LVIS into the treatment of refractory occlusion due to hard clot embolization at the paraclinoid segment, and the outcomes were preferable because of the higher visibility, higher flexibility, and lower cell size of LVIS.

Differences in Safety and Efficacy of Endovascular Treatment for Acute Ischemic Stroke : A Propensity Score Analysis of Intracranial Atherosclerosis-Related Occlusion versus Embolism.

PURPOSE: The prognosis after endovascular treatment (EVT) of acute arterial occlusions due to intracranial atherosclerotic disease (ICAD) may differ from those due to embolism. The aim was to evaluate whether safety and efficacy of EVT differ among patients with middle cerebral artery (MCA) M1 occlusion from ICAD or embolism. METHODS: A database review was conducted to identify EVT patients with acute MCA M1 occlusion from November 2013 to December 2018.The patients were divided into the ICAD group and embolic group according to the etiology of occlusion. Using propensity score analysis, patients with ICAD-related occlusion and embolism underwent 1:1 matching. Angiographic results, complications, and clinical outcomes were compared. RESULTS: A total of 217 patients (ICAD: 51; embolism: 166) were identified. After propensity score matching, 45 patients with ICAD-related occlusion and 45 with embolism were matched. All baseline covariates except atrial fibrillation were statistically indistinguishable. The rate of successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] 2b-3) was similar between the two groups, while the rate of mTICI 3 in the ICAD group was higher. No statistical difference was observed in the rate of postprocedural intracranial hemorrhage. The rate of favorable outcome (modified Rankin Scale [mRS] ≤2) and mortality at 90 days was comparable. CONCLUSION: This propensity score analysis demonstrated that the EVT patients with acute ICAD-related MCA M1 occlusion had similar angiographic and clinical outcomes compared to those with M1 embolism on a similar baseline condition.

Higher Baseline Cortical Score Predicts Good Outcome in Patients With Low Alberta Stroke Program Early Computed Tomography Score Treated with Endovascular Treatment.

BACKGROUND: Patients with large vessel occlusion and noncontrast computed tomography (CT) Alberta Stroke Program Early CT Score (ASPECTS) <6 may benefit from endovascular treatment (EVT). There is uncertainty about who will benefit from it. OBJECTIVE: To explore the predicting factors for good outcome in patients with ASPECTS <6 treated with EVT. METHODS: We retrospectively reviewed 60 patients with ASPECTS <6 treated with EVT in our center between March 2018 and June 2019. Patients were divided into 2 groups because of the modified Rankin Score (mRS) at 90 d: good outcome group (mRS 0-2) and poor outcome group (mRS ≥3). Baseline and procedural characteristics were collected for unilateral variate and multivariate regression analyses to explore the influent variates for good outcome. RESULTS: Good outcome (mRS 0-2) was achieved in 24 (40%) patients after EVT and mortality was 20% for 90 d. Compared with the poor outcome group, higher baseline cortical ASPECTS (c-ASPECTS), lower intracranial hemorrhage, and malignant brain edema after thrombectomy were noted in the good outcome group (all P < .01). Multivariate logistic regression showed that only baseline c-ASPECTS (≥3) was positive factor for good outcome (odds ratio = 4.29; 95% CI, 1.21-15.20; P = .024). The receiver operating characteristics curve indicated a moderate value of c-ASPECTS for predicting good outcome, with the area under receiver operating characteristics curve 0.70 (95% CI, 0.56-0.83; P = .011). CONCLUSION: Higher baseline c-ASPECTS was a predictor for good clinical outcome in patients with ASPECTS <6 treated with EVT, which could be helpful to treatment decision.

Current knowledge of large vascular occlusion due to intracranial atherosclerosis: focusing on early diagnosis.

Intracranial atherosclerosis (ICAS)-related large vascular occlusion (LVO) was an intractable subtype of acute ischemic stroke (AIS), which always needed rescue angioplasty and stenting and complicated the procedure of endovascular recanalization. Diagnosing ICAS-LVO accurately and early was helpful for both clinical treatment and trials. Digital subtraction angiography (DSA) was unable to provide an early and rapid diagnosis of ICAS-LVO based on current studies. A variety of pre-DSA methods had been used to distinguish ICAS-LVO with other subtypes of ischemic stroke, such as medical histories, clinical presentations, computed tomography or angiography (CT/CTA), and magnetic resonance imaging (MRI/MRA). This article briefly reviewed the status quo of the diagnosis and treatment of ICAS-LVO and summarized early diagnostic methods of ICAS-LVO from different aspects.