Advances in endovascular treatment of acute ischaemic stroke from intracranial large vessel occlusions have continued in the past decade. Here, we performed a detailed review of all the new trials ...and studies that had the highest evidence, the guidelines for mechanical thrombectomy, the selection of the particular population outside the guidelines and endovascular therapeutic strategies for acute ischemic stroke from occluded intracranial arteries.
Aims
In previous studies, numerous differential microRNAs (miRNAs) in cerebral ischemic/reperfusion (I/R) injury were identified using the miRNA microarray analysis. However, the relationship between ...miRNA and cerebral I/R injury remains largely unknown. In this study, we investigated the function and explored the possible mechanism of miR‐224‐3p in cerebral I/R injury.
Methods
Oxygen glucose deprivation model in N2a cells were used to perform the cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase‐3 were measured to evaluate the function of miR‐224‐3p.
Results
Overexpression of miR‐224‐3p alleviated the apoptosis induced by oxygen glucose deprivation (OGD) and cleaved caspase‐3 was significantly reduced. We further provided the possible mechanism that miR‐224‐3p may protect cells from cerebral I/R injury by targeting FAK family‐interacting protein (FIP200). Further rescue experiment proved that overexpression of FIP200 partially blocked the effect of miR‐224‐3p.
Conclusions
We evaluated the function and mechanism of miR‐224‐3p in ischemic brain injury. miR‐224‐3p may serve as a potential target for new therapeutic intervention.
We evaluated the function and mechanism of miR‐224‐3p in ischemic brain injury. miR‐224‐3p may serve as a potential target for new therapeutic intervention.
We aimed to investigate the role of pretreatment collateral status in predicting the efficacy and safety of endovascular treatment (EVT) in acute ischaemic stroke due to cervical and/or cerebral ...arterial occlusions.
Relevant full-text articles published since 1 January 2000, investigating correlations between collateral status and any efficacy or safety outcome in patients undergoing EVT in cohort or case-control studies, or randomised clinical trials, were retrieved by PubMed and manual search. Two authors extracted data from eligible studies and assessed study quality. Risk ratios (RR) were pooled for good versus poor collaterals for outcomes based on a random-effects model. Sensitivity and subgroup analyses were conducted.
In total, 35 (3542 participants) and 23 (2652 participants) studies were included in qualitative review and quantitative meta-analysis, respectively. Overall, good pretreatment collaterals increased the rate of favourable functional outcome at 3 months (RR=1.98, 95% CI 1.64 to 2.38; p<0.001), and reduced the risks of periprocedural symptomatic intracranial haemorrhage (RR=0.59, 95% CI 0.43 to 0.81; p=0.001) and 3-month mortality (RR=0.49, 95% CI 0.38 to 0.63; p<0.001), as compared with poor collaterals, in patients with acute ischaemic stroke under EVT. No individual study could alter the estimate of overall effect of collateral status, but there were moderate to significant heterogeneities between subgroups of studies with different modes of EVT, different arterial occlusions and different collateral grading methods.
Good pretreatment collateral status is associated with higher rates of favourable functional outcome, and lower rates of symptomatic intracranial haemorrhage and mortality, in patients with acute ischaemic stroke receiving endovascular therapies.
MicroRNAs (miRNAs) are implicated in the progression of ischemic stroke (IS) and bone marrow-derived mesenchymal stem cells (BMSCs)-derived exosomes play a role in IS therapy. Herein we hypothesized ...that the BMSCs-derived exosomes containing overexpressed miR-138-5p could protect the astrocytes following IS involved with lipocalin 2 (LCN2).
The differentially expressed gene related to IS was initially identified by bioinformatics analysis. miR-138-5p was predicted to regulate LCN2. The expression of miR-138-5p and LCN2 was altered in the oxygen-glucose deprivation (OGD)-induced astrocytes. Furthermore, the cell behaviors and inflammatory responses were evaluated both in astrocytes alone and astrocytes co-cultured with exosomes derived from BMSCs overexpressing miR-138-5p to explore the involvement of miR-138-5p and LCN2 in IS. Besides, middle cerebral artery occlusion (MCAO) mouse model was established to explore the effect of BMSCs-derived exosomal miR-138-5p in IS in vivo.
LCN2 was highly expressed in IS. Besides, LCN2 was a target gene of miR-138-5p. BMSCs-derived exosomes could be endocytosed by astrocytes via co-culture. Overexpression of miR-138-5p promoted the proliferation and inhibited apoptosis of astrocytes injured by OGD, accompanied by the reduced expression of inflammatory factors, which was achieved by down-regulating LCN2. More importantly, BMSCs delivered miR-138-5p to the astrocytes via exosomes and BMSCs-derived exosomal miR-138-5p alleviated neuron injury in IS mice.
BMSCs-derived exosomal miR-138-5p reduces neurological impairment by promoting proliferation and inhibiting inflammatory responses of astrocytes following IS by targeting LCN2, which may provide a novel target for IS treatment.
There were limited studies comparing the anterior (AC) and posterior (PC) circulation acute ischemic strokes (AIS). Our study aimed to evaluate distinct features of AC and PC strokes regarding ...clinical, vascular risk, pathogenesis and outcome factors after endovascular procedures. This multicenter prospective study registered 873 patients with acute large occlusion of anterior circulation stroke (ACS) and posterior circulation stroke (PCS). Patients who underwent endovascular procedures were included in this study. The differences in ACS and PCS regarding baseline characteristics, post-operative intracranial hemorrhage and outcomes were evaluated. A total of 741 patients were included in the data analysis. Intravenous thrombolysis (31.5%), atrial fibrillation (22.7%) and stent thrombectomy (82.4%) were more frequently observed in ACS patients. While higher NIHSS score, hypertension (67.6%) and balloon angioplasty (20.7%) were more prevalent in PCS patients. Symptomatic intracranial hemorrhage was more common in ACS (7.4% vs 2.8%). However, a 3-month follow-up outcomes were better in ACS with higher functional independence and low mortality rate than PCS (46.8% vs 30.3% and 16.4% vs 33.8%, respectively,
P
< 0.01). In this large prospective study, there were significant differences in the pathogenesis of stroke and treatment procedure between ACS and PCS which influence the clinical outcome. These findings could lead to a tailored clinical procedures and treatment strategies to improve the prognosis in both groups.
Although recent trials have suggested that stenting is worse than medical therapy for patients with severe symptomatic intracranial atherosclerotic stenosis, it is not clear whether this conclusion ...applies to a subset of patients with hypoperfusion symptoms. To justify for a new trial in China, we performed a multicenter prospective registry study to evaluate the safety and efficacy of endovascular stenting within 30 days for patients with severe symptomatic intracranial atherosclerotic stenosis.
Patients with symptomatic intracranial atherosclerotic stenosis caused by 70% to 99% stenosis combined with poor collaterals were enrolled. The patients were treated either with balloon-mounted stent or with balloon predilation plus self-expanding stent as determined by the operators following a guideline. The primary outcome within 30 days is stroke, transient ischemic attack, and death after stenting. The secondary outcome is successful revascularization. The baseline characteristics and outcomes of the 2 treatment groups were compared.
From September 2013 to January 2015, among 354 consecutive patients, 300 patients (aged 58.3±9.78 years) were recruited, including 159 patients treated with balloon-mounted stent and 141 patients with balloon plus self-expanding stent. The 30-day rate of stroke, transient ischemic attack, and death was 4.3%. Successful revascularization was 97.3%. Patients treated with balloon-mounted stent were older, less likely to have middle cerebral artery lesions, more likely to have vertebral artery lesions, more likely to have Mori A lesions, less likely to have Mori C lesions, and likely to have lower degree of residual stenosis than patients treated with balloon plus self-expanding stent.
The short-term safety and efficacy of endovascular stenting for patients with severe symptomatic intracranial atherosclerotic stenosis in China is acceptable. Balloon-mounted stent may have lower degree of residual stenosis than self-expanding stent.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01968122.
Endovascular treatment (EVT) is now considered the gold standard for select patient populations with anterior circulation stroke; however, data on the treatment of posterior circulation stroke are ...less clear. This study aims to determine the characteristics and treatment outcomes of patients with acute basilar artery occlusion (BAO) and to evaluate the effectiveness and safety of EVT for patients with acute BAO in a high-volume stroke center.
This study included 187 consecutive patients with acute BAO who underwent EVT from January 2012 to July 2018 in the Beijing Tiantan Hospital. The baseline characteristics, procedure parameters, and functional outcome were assessed.
Among the 187 patients, 138 (73.8%) underwent mechanical thrombectomy with a stent retriever, 33 (17.6%) underwent direct intracranial angioplasty (balloon dilation and/or stent implantation) for underlying severe intracranial atherosclerotic disease, and 91 (48.7%) underwent combined mechanical thrombectomy and angioplasty. Successful recanalization modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b-3 was achieved in 158 patients (84.5%). Overall, the rates of functional independence modified Rankin Scale (mRS) 0-2 and favorable outcome (mRS 0-3) at 90 days were 36.4 and 49.2%, respectively, and 90-day all-cause mortality was 20.3%.
EVT was effective and safe for treating patients with acute BAO.
Three-dimensional pseudocontinuous arterial spin labeling with multiple postlabeling delays has been used to assess cerebral blood flow (CBF). We used this modality to estimate antegrade and ...collateral flow in patients with unilateral middle cerebral artery stenosis.
Consecutive patients with unilateral middle cerebral artery 50% to 99% stenosis at 2 centers underwent pseudocontinuous arterial spin labeling with a postlabeling delays of 1.5 and 2.5 s. Mean CBF of bilateral middle cerebral artery territory at the postlabeling delays 1.5 and 2.5 s was measured. Early-arriving flow proportion was defined as (CBF 1.5 s at lesion side/CBF 2.5 s at normal side)×100%. Late-arriving retrograde flow proportion was defined as (CBF 2.5 s-CBF 1.5 s at lesion side-CBF 2.5 s-CBF 1.5 s at normal side)/CBF 2.5 s at normal side×100%. Antegrade and collateral scales were evaluated in patients with conventional angiography. Spearman correlation coefficients were calculated between early-arriving flow and late-arriving retrograde flow proportions on arterial spin labeling and antegrade and collateral scales on conventional angiography, respectively.
Forty-one patients (46.0±12.0 years) were enrolled. The mean early-arriving flow proportion was 78.3±14.9%. The mean late-arriving retrograde flow proportion was 16.1±10.2%. In 21 patients with conventional angiography, Spearman correlation coefficient was 0.53 (95% confidence interval, 0.11-0.79) between antegrade grade and early-arriving flow proportion (P=0.01) and 0.81 (95% confidence interval, 0.56-0.92) between collateral grade and late-arriving retrograde flow proportion (P<0.0001).
Three-dimensional pseudocontinuous arterial spin labeling with 2 postlabeling delays may provide an empirical approach for estimating antegrade and collateral flow in patients with unilateral middle cerebral artery stenosis.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02479243.
Aim: The impact of international normalized ratio (INR) on prognosis after acute ischemic stroke without anticoagulation therapy is unclear. Herein, the association between baseline INR and stroke ...outcomes in patients without anticoagulation therapy was investigated.Methods: A total of 14,782 ischemic stroke patients from the China National Stroke Registry Ⅱ were included in this analysis. The period of follow-up was 1 year after stroke onset. Multivariate logistic regression models were used to estimate the relationship between INR and stroke outcomes including all-cause death, recurrent stroke, composite end point, and poor functional outcome.Results: Of 14,782 patients with stroke, all-cause death occurred in 1080 (7.3%), recurrence stroke in 538 (3.9%), combined end point in 1319 (8.9%), and poor functional outcome in 3001 (20.3%). Compared with the medium INR group (0.9–1.1), the odds ratios with confidence intervals of 95% for the high INR group (＞1.1) were 1.58 (1.32–1.98) for all-cause death, 1.40 (1.10–1.79) for stroke recurrence, 1.52 (1.29–1.79) for combined end point, and 1.21 (1.06–1.39) for poor functional outcome. No association between low INR (＜0.9) and any stroke outcomes was found compared with the medium group.Conclusions: Increased admission INR was associated with adverse stroke outcomes among acute ischemic stroke patients without atrial fibrillation or anticoagulation therapy.
Pre-treatment collateral status may be associated with the rates of successful revascularization in acute ischemic stroke patients receiving endovascular treatment (EVT). We conducted a systematic ...review and meta-analysis to synthesize relevant evidence currently available.
Relevant full-text articles published in English since January 1, 2000, reporting associations between collateral status and successful reperfusion and/or recanalization in acute ischemic stroke patients receiving EVT in cohort or case-control studies, or randomized clinical trials, were retrieved through search of PubMed. Study selection, data extraction and study quality assessment were carried out by 2 investigators. Risk ratios (RR) were pooled for good vs. poor collaterals for the outcomes of successful reperfusion and recanalization, based on random-effects models. Subgroup analyses were conducted to explore for potential factors that might interfere with the effects of pre-treatment collateral status on reperfusion by EVT.
In total, 27 studies (2,366 subjects) were included in qualitative analysis, among which 24 studies (2,239 subjects) were quantitatively analyzed. Overall, good pre-treatment collaterals significantly increased the rate of both successful reperfusion (RR 1.28, 95% CI 1.17-1.40; p < 0.001) and recanalization (RR 1.23, 95% CI 1.06-1.42; p = 0.006), as compared with poor collaterals. Subgroup analyses revealed that the effects of collateral status on successful reperfusion by EVT might be different between populations with different ethnicities.
Good pre-treatment collaterals may enhance the rates of successful reperfusion and recanalization in EVT for acute ischemic stroke. This may partly explain the favorable effects of good pre-treatment collaterals on clinical outcomes of stroke patients receiving EVT. Thus, it would be valuable to assess the collateral status prior to EVT in acute ischemic stroke. But studies are needed to further verify if the positive effects of good collaterals on revascularization by EVT are restricted to certain subgroups of patients.
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