Safety and Efficacy of Aspiration Catheter CAT6 and 5 Fr Navien in the Endovascular Treatment of Acute Ischemic Stroke.

BACKGROUND: Mechanical thrombectomy has become a key treatment option for acute ischemic stroke. This study compared the safety and efficacy of aspiration catheter CAT6 and 5 Fr Navien. METHODS: Thrombectomy was performed in103 patients with the acute internal carotid artery, middle cerebral artery M1 or M2 occlusions, including the CAT6 group (n=53 with stent retriever and CAT6 aspiration) and the 5 Fr Navien group (n=50 with stent retriever and 5 Fr Navien aspiration) at the Advanced Stroke Center. RESULTS: Overall, an aspiration catheter placement success rate was achieved in 93.2% of cases, 52 (98.11%) for CAT6, and 44 (88.00%) for 5 Fr Navien ( P =0.042). Overall, 17 cases (16.51%) required additional guidewire rates, 5.66% for CAT6, and 13.592% for 5 Fr Navien ( P =0.002). First-pass success rate (FPSR) was achieved in 38.84% of cases overall, a rate that did not differ significantly between catheters: 45.28% for CAT6; 32.00% for 5 Fr Navien ( P =0.167). Final thrombolysis in cerebral infarction 2b or 3 reperfusion was achieved in 91.26% of cases overall, 51 (96.23%) for CAT6, and 43 (86%) for 5 Fr Navien ( P =0.066). The participants had a mean number of passes for the index thrombus of 1.956 and a median procedure time of 65.82±21.8 minutes. There was no significant difference found in 90-day good outcome (mean 42.7%, modified Rankin Score 0 to 2) and 90-day mortality (17%) between CAT6 and 5 Fr Navien. CONCLUSION: Aspiration catheter placement success rate and first-pass success rate seemed to be higher for CAT6 and, moreover, the rate of additional guidewires was lower.

Postoperative blood glucose increase is associated with futile recanalization in patients with successful thrombectomy: a retrospective study.

BACKGROUND: Timely recognition of futile recanalization might enable a prompt response and an improved outcome in post-thrombectomy patients. This study aims to evaluate whether postoperative blood glucose increase (BGI) could act as an indicator of futile recanalization in patients receiving a successful thrombectomy. METHODS: This is a single-center, retrospective analysis of patients with anterior circulation large-vessel occlusion and successful thrombectomy between February 2019 and June 2022. BGI was defined as a higher level of blood glucose at the first postoperative morning than at admission. Futile recanalization was defined as patients with a modified Rankin Scale score of 3-6 at 90 days after onset. Multivariable binary logistic regression was used to assess the association of BGI with futile recanalization. RESULTS: A total of 276 patients were enrolled, amongst which 120 patients (43.5%) had BGI. Futile recanalization was more prevalent among patients with BGI compared to those without (70.0 vs. 49.4%, P = 0.001). After adjusting for potential confounders, BGI was associated with a higher likelihood of futile recanalization (adjusted OR: 2.97, 95%CI: 1.50-5.86, P = 0.002). This association was consistently observed regardless of diabetes history, occlusion site, time from symptom onset to groin puncture, or reperfusion status. CONCLUSION: Our findings support BGI serving as an indicator of futile recanalization in patients with anterior circulation large-vessel occlusion and successful thrombectomy.

Postoperative fibrinogen-to-albumin ratio acting as an indicator of futile recanalization in patients with successful thrombectomy.

BACKGROUND: Timely recognition of futile recanalization might enable a prompter response and thus improve outcomes in patients receiving successful thrombectomy. This study aims to evaluate whether postoperative fibrinogen-to-albumin ratio (FAR) could act as an indicator of futile recanalization. METHODS: This is a single-center, retrospective analysis of patients with acute anterior circulation large-vessel occlusion and successful thrombectomy between May 2019 and June 2022. FAR was defined as postoperative blood levels of fibrinogen divided by those of albumin, and dichotomized into high and low levels based on the Youden index. Futile recanalization was defined as patients achieving a successful recanalization with a modified Rankin Scale score of 3-6 at 90 days. Multivariable logistic regression was used to assess the association of FAR with futile recanalization. RESULTS: A total of 255 patients were enrolled, amongst which 87 patients (34.1%) had high postoperative FAR. Futile recanalization was more prevalent among patients with high FAR compared to those with low FAR (74.7% vs. 53.0%, p = .001). After adjusting for potential confounders, high postoperative FAR was found to independently correspond with the occurrence of futile recanalization (adjusted OR 2.40, 95%CI 1.18-4.87, p = .015). This association was consistently observed regardless of prior antithrombotic therapy, treatment of intravenous thrombolysis, occlusion site, time from symptom onset to groin puncture, and reperfusion status. CONCLUSION: Our findings support high postoperative FAR serving as an indicator of futile recanalization in patients with anterior circulation large-vessel occlusion and successful thrombectomy.

CircCRIM1/microRNA-141-3p/thioredoxin-binding protein axis mediates neuronal apoptosis after cerebral ischemia-reperfusion.

Numerous studies have indicated enrichment of circular RNA (circRNA) in the brain takes on a momentous role in cerebral ischemia-reperfusion (CIR) injury. A recent study discovered a novel circCRIM1, was highly expressed in the middle cerebral artery occlusion-reperfusion (MCAO/R) model. Nevertheless, its specific biological function remained unknown. The study was to explore circCRIM1 in CIR-induced neuronal apoptosis. As measured, circCRIM1 and TXNIP were up-regulated, while miR-141-3p was down-regulated in MCAO/R mouse model and OGD/R SH-SY5Y cells. Depleting circCRIM1 reduced the number of apoptotic neurons in MCAO/R rats, increased the number of Nissl bodies, prevented reactive oxygen species production and oxidative stress imbalance in brain tissues, repressed cleaved caspase-3, Bax, and Cyto C protein levels and increased Bcl-2 levels. Overexpression of circCRIM1 further repressed neuronal activity and accelerated apoptosis in OGD/R model, disrupted redox balance. Depleting circCRIM1 had the opposite effect in OGD/R model. Knocking down miR-141-3p or TXNIP weakened the effects of knocking down circCRIM1 or overexpressing circCRIM1, separately. Mechanistically, circCRIM1 exerted an active role in CIR injury via miR-141-3p to mediate TXNIP. All in all, the circCRIM1/miR-141-3p/TXNIP axis might be a latent therapeutic target for CIR injury.

Impact of volemia at admission on the effect of collateral status on functional outcomes in patients undergoing endovascular thrombectomy.

BACKGROUND AND PURPOSE: Having good collaterals is associated with better clinical outcomes in patients undergoing endovascular thrombectomy. This study aims to evaluate whether the effect of collateral status on functional outcomes is modified by volemia at admission. METHODS: This is a single-center, retrospective analysis of patients who had acute proximal anterior circulation occlusion and underwent endovascular thrombectomy between January 2019 and June 2022. Volemia at admission, evaluated by blood urea nitrogen-to-creatinine ratio, was used to dichotomize patients into dehydrated and hydrated groups. The primary outcome was functional independence (90-day modified Rankin Scale score = 0-2). Secondary outcomes were the rates of successful reperfusion, 24-h symptomatic intracranial hemorrhage, and 90-day all-cause mortality. Multivariable logistic regression analysis was used to assess the interaction between collateral status and volemia at admission on outcomes. RESULTS: A total of 290 patients were enrolled, among whom having good collaterals was associated with functional independence (adjusted odds ratio [OR] = 2.71, 95% confidence interval [CI] = 1.41-5.22, p = 0.003). Having good collaterals benefited dehydrated patients (adjusted OR = 3.33, 95% CI = 1.45-7.63, p = 0.004) but not hydrated patients (adjusted OR = 2.21, 95% CI = 0.73-6.68, p = 0.161). However, an interaction between collaterals and volemia at admission on functional independence was not observed (p = 0.319). The rates of successful reperfusion, symptomatic intracerebral hemorrhage, and all-cause mortality were similar between those with good and poor collaterals in both dehydrated and hydrated patients. CONCLUSIONS: The effect of collateral status on the functional independence of patients undergoing thrombectomy is not modified by volemia at admission.

The effect of intravenous thrombolysis on patients with successful thrombectomy depends on final reperfusion grade: A retrospective study.

AIMS: Although intravenous thrombolysis (IVT) has not shown confirmative effects on the outcomes of patients receiving successful thrombectomy, it might influence the outcomes of a subset of these patients. This study aims to evaluate whether the effects of IVT depend on final reperfusion grade in patients with successful thrombectomy. METHODS: This is a single-center, retrospective analysis of patients with an acute anterior circulation large-vessel occlusion and a successful thrombectomy between January 2020 and June 2022. Final reperfusion grade was evaluated by the modified Thrombolysis in Cerebral Infarction (mTICI) score, which was dichotomized into incomplete (mTICI 2b) and complete (mTICI 3) reperfusion. The primary outcome was functional independence (90-day modified Rankin Scale score 0-2). Safety outcomes were 24-h symptomatic intracranial hemorrhage and 90-day all-cause mortality. Multivariable logistic regression analyses were used to assess the interactions between IVT treatment and final reperfusion grade on outcomes. RESULTS: When comparing all 167 patients enrolled in the study, IVT did not influence the extent of functional independence (adjusted OR: 1.38; 95% CI: 0.65-2.95; p = 0.397). The effect of IVT on functional independence depended on final reperfusion grade (p = 0.016). IVT benefited patients with incomplete reperfusion (adjusted OR: 3.70; 95% CI 1.21-11.30; p = 0.022), but not those with complete reperfusion (adjusted OR: 0.48, 95% CI: 0.14-1.59; p = 0.229). IVT was not associated with 24-h symptomatic intracerebral hemorrhage (p = 0.190) or 90-day all-cause mortality (p = 0.545). CONCLUSIONS: The effect of IVT on functional independence depended on final reperfusion grade in patients with successful thrombectomy. IVT appeared to benefit patients with incomplete reperfusion, but not those with complete reperfusion. Because reperfusion grade cannot be determined prior to endovascular treatment, this study argues against withholding IVT in IVT-eligible patients.

Circular RNA PUM1 performs as a competing endogenous RNA of microRNA-340-5p to mediate DEAD-box helicase 5 to mitigate cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion damages local brain tissue and impairs brain function, but its specific pathogenesis is still uncertain. Recent studies have clarified circPUM1 is aberrantly elevated in cerebral ischemia-reperfusion injury; however, circPUM1's function in cerebral ischemia-reperfusion-induced neuronal injury remains ambiguous. The results illustrated circPUM1 and DEAD-box helicase 5 were decreased, but microRNA-340-5p was elevated in transient middle cerebral artery occlusion mice and oxygen glucose deprivation/reoxygenation-treated SH-SY5Y cells. Knockdown of circPUM1 aggravated the neuronal injury in transient middle cerebral artery occlusion mice and motivated glial cell activation, neuronal apoptosis and inflammation. Enhancing circPUM1 restrained oxygen glucose deprivation/reoxygenation-induced SH-SY5Y cell apoptosis, the release of lactate dehydrogenase and inflammatory factors, and activation of nuclear factor-kappaB pathway, while elevating microRNA-340-5p aggravated oxygen glucose deprivation/reoxygenation-induced cell damage. Functional rescue experiments exhibited that the impacts of knockdown or enhancement of circPUM1 were turned around by microRNA-340-5p downregulation and DEAD-box helicase 5 silencing, respectively. Moreover, it was demonstrated that circPUM1 competitively adsorbed microRNA-340-5p to mediate DEAD-box helicase 5. All in all, this study clarifies that circPUM1 mitigates cerebral ischemia-reperfusion-induced neuronal injury by targeting the microRNA-340-5p/DEAD-box helicase 5 axis.

Simplified classification of cavernous internal carotid artery tortuosity: a predictor of procedural complexity and clinical outcomes in mechanical thrombectomy.

OBJECTIVES: Thromboaspiration catheters are increasingly used for the endovascular treatment of large vessel stroke (LVS), while tortuous vascular anatomy still remains one major challenge in mechanical thrombectomy. Prompt assessing and understanding cavernous internal carotid artery (cICA) tortuosity may help to predict procedural complexities of mechanical thrombectomy and thus improve the clinical outcomes. METHODS: A retrospective review was performed on a cohort of LVS patients with thromboaspiration catheter. Simplified classification of cICA tortuosity was applied by measurement of the angle of the posterior genus (P) and the height from the peak of the posterior genu to the trough of the anterior genu (D). Statistical analyses were performed to analyze differences among the obtained types of cICA tortuosity regarding procedural characteristics and clinical outcomes. RESULTS: A total of 150 patients with LVS proximal to the internal ICA terminus and middle cerebral artery (MCA) were included in this study, and three types of cICA tortuosity were defined by the simplified classification. The index, such as patients ages and hypertension, procedural fluoroscopy time, the degree of cICA tortuosity, first-pass success, final reperfusion, and 90-day mortality showed significant differences among the three types (P < 0.05), while 90-day good outcome (mRS 0-2) only presented significant difference between Type I and Type III (P < 0.05). CONCLUSIONS: The study indicated that the grading of cICA tortuosity is highly correlated with procedural complexity and clinical outcome in mechanical thrombectomy. The proposed classification system may be helpful in pre-procedure prognostication complexity and clinical outcomes.Abbreviations:LVS: large vessel stroke; cICA: cavernous internal carotid artery; mRS: modified Rankin Scale; AIS: acute ischemic stroke; MCA: middle cerebral artery; M1: first division of middle cerebral artery; M2: second division of middle cerebral artery; M3: third division of middle cerebral artery; TICI: Thrombolysis In Cerebral Infarction; TICI 2b: two-thirds of occluded territory reperfusion; DSA: digital subtraction angiography; FT: fluoroscopy time.

Depleting SOX2 improves ischemic stroke via lncRNA PVT1/microRNA-24-3p/STAT3 axis.

OBJECTIVES: Studies have widely explored in the filed of ischemic stroke (IS) with their focus on transcription factors. However, few studies have pivoted on sex determining region Y-box 2 (SOX2) in IS. Thus, this study is launched to figure out the mechanisms of SOX2 in IS. METHODS: Rat middle cerebral artery occlusion (MCAO) was established as a stroke model. MCAO rats were injected with depleted SOX2 or long non-coding RNA plasmacytoma variant translocation 1 (PVT1) to explore their roles in neurological deficits, cerebral water content, neuron survival, apoptosis and oxidative stress. The relationship among SOX2, PVT1, microRNA (miR)-24-3p and signal transducer and activator of transcription 3 (STAT3) was verified by a series of experiments. RESULTS: SOX2, PVT1 and STAT3 were highly expressed while miR-24-3p was poorly expressed in cerebral cortex tissues of MCAO rats. Depleted SOX2 or PVT1 alleviated brain injury in MCAO rats as reflected by neuronal apoptosis and oxidative stress restriction, brain water content reduction, and neurological deficit and neuron survival improvements. Overexpression of PVT1 functioned oppositely. Restored miR-24-3p abolished PVT1 overexpression-induced brain injury in MCAO rats. SOX2 directly promoted PVT1 expression and further increased STAT3 by sponging miR-24-3p. CONCLUSION: This study presents that depleting SOX2 improves IS via PVT1/miR-24-3p/STAT3 axis which may broaden our knowledge about the mechanisms of SOX2/PVT1/miR-24-3p/STAT3 axis and provide a reference of therapy for IS.

Glycine Improves Ischemic Stroke Through miR-19a-3p/AMPK/GSK-3ß/HO-1 Pathway.

PURPOSE: To explore the molecular mechanism of glycine in improving ischemic stroke. PATIENTS AND METHODS: The serum samples of patients with ischemic stroke and healthy people were compared. The ischemic stroke model of PC12 cells was established by oxygen-glucose deprivation (OGD). qPCR quantified miR-19a-3p and AMPK mRNA, and protein expression was detected by Western blot. MTT was used to detect cell activity. Flow cytometry was used to detect cells. Glucose metabolism kit was used to detect glucose intake and formation amount of lactic acid. RESULTS: Compared with the control group, OGD group (OGDG) showed lower cell activity and increased cell apoptosis. TNF-α, IL-1ßI, L-6, Caspase 3, Caspase 9 and Bax were up-regulated, and Glut1, HK2, LDHA, PDK1, PKM2 and Bcl2 were down-regulated. At the same time, glucose intake, formation amount of lactic acid and cell apoptosis rate were reduced, and AMPK/GSK-3ß/HO-1 pathway activity was down-regulated. Glycine could counteract the above phenomena in OGDG. miR-19a-3p and AMPK decreased and increased, respectively, during glycine therapy. AMPK was the target gene of miR-19a-3p. Rescue experiments demonstrated that glycine improved cell apoptosis, inflammatory response and glucose metabolism disorder of ischemic stroke through miR-19a-3p/AMPK/GSK-3ß/HO-1 pathway. CONCLUSION: Glycine improves ischemic stroke through miR-19a-3p/AMPK/GSK-3ß/HO-1 pathway.

The effect of glutamate-induced excitotoxicity on DNA methylation in astrocytes in a new in vitro neuron-astrocyte-endothelium co-culture system.

Glutamate-induced excitotoxicity is a contributer to many neurological diseases. Astrocytes may represent a new target for treating glutamate-induced excitotoxicity. However, the in vitro culture system that mimics the in vivo microenvironment is lacking. This study aimed to establish a new in vitro co-culture system including neurons, astrocytes, and endothelial cells (NAE), and to investigate the effect of glutamate-induced excitotoxicity on DNA methylation in astrocytes. A NAE co-culture method was created using a Transwell chamber, in which neurons were seeded on the bottom of the lower chamber, endothelial cells were plated on the top membrane, and astrocytes were plated on the bottom membrane of the insert. Glutamate-induced toxicity was induced using glutamate and glycine, and examined using immunofluorescence and lactate dehydrogenase release assay. Global methylation in astrocytes was analyzed, and the expression of DNMT1 and DNMT3a was examined using Western blot analysis. Glutamate treatment induced less neuronal damage in the NAE system compared with the control group in which neurons and astrocytes were cultured alone. Global DNA methylation was increased and the expression of DNMT1 and DNMT3a in astrocytes was increased after glutamate treatment, which was blocked by application of the NMDAR inhibitor MK-801 and the DNMT inhibitor 5-azaC from the endothelial cells. The in vitro ANE culture system is effective for studying glutamate-induced excitotoxicity, and may be used for testing the passage of drugs across the blood-brain barrier. Inhibition of DNA methylation in astrocytes may be a new therapeutic strategy for treating glutamate-induced excitotoxicity.