Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial.

Importance: Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022. Interventions: Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.

MiR-410 exerts neuroprotective effects in a cellular model of Parkinson's disease induced by 6-hydroxydopamine via inhibiting the PTEN/AKT/mTOR signaling pathway.

Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by loss of dopaminergic neurons in the substantia nigra. Recently, microRNAs (miRNAs) were emerging as important mediators in dopaminergic neuron biology. This study determined miR-410 expression in the 6-hydroxydopamine (6-OHDA)-induced in vitro cellular model of PD and explored the mechanistic role of miR-410 in the modulation of neuronal cell viability and apoptosis. Our data showed that 6-OHDA concentration-dependently suppressed neuronal cell viability and miR-410 expression in SH-SY5Y and PC12 cells. Overexpression of miR-410 partially restored the effects of 6-OHDA on neuronal cell viability, apoptosis, capsase-3 activity as well as reactive oxygen species (ROS) production. On the other hand, inhibition of miR-410 decreased neuronal cell viability and increased apoptotic rates, capase-3 activity as well as ROS production. Furthermore, the potential targets of miR-410 were predicted by TargetScan tool, and we verified that phosphatase and tensin homolog (PTEN) was a target of miR-410 as confirmed by the dual-luciferase reporter assay. MiR-410 overexpression attenuated PTEN expression and mediated the effects in the 6-OHDA-treated cells via targeting PTEN in SH-SY5Y and PC12 cells. Furthermore, 6-OHDA treatment suppressed the protein expression of phosphorylated AKT and phosphorylated mTOR, which was partially attenuated by miR-410 overexpression in SH-SY5Y and PC12 cells. MiR-410 overexpression increased phosphorylated AKT and phosphorylated mTOR protein expression, and this effect was attenuated by PTEN overexpression in both SH-SY5Y and PC12 cells. Collectively, this is the first study to demonstrate the neuroprotective effects of miR-410 in a 6-OHDA-induced cellular model of PD, and our data implied that miR-410 exerted its neuroprotective effects via regulating PTEN/AKT/mTOR signaling axis. The present study may suggest new paradigm to study the pathology of PD.

Association Between Blood-Brain Barrier Disruption and Stroke-Associated Pneumonia in Acute Ischemic Stroke Patients After Endovascular Therapy: A Retrospective Cohort Study.

Background: Stroke, particularly due to large vessel occlusion (LVO), is a major cause of mortality and disability globally. Endovascular therapy (ET) significantly improves outcomes for acute ischemic stroke (AIS) patients, but complications such as stroke-associated pneumonia (SAP) increase mortality and healthcare costs. This study investigates the association between blood-brain barrier (BBB) disruption and the increased risk of SAP and explores the relationship between BBB disruption and medium-term functional outcomes. Methods: The retrospective cohort study was performed on AIS patients enrolled between January 2019 to February 2023 who underwent ET. Patients were divided into two groups: BBB disruption and without BBB disruption. Multiple logistic regression model was conducted to measure the association between BBB disruption and SAP. Mediation analysis was used to estimate the potential mediation effects on the associations of BBB disruption with SAP. A restricted cubic spline (RCS) regression model was used to further outline the connection between the highest CT value of hyperattenuated lesions areas and the risk of SAP. Results: The study included 254 patients who underwent endovascular therapy, with 155 patients in the BBB disruption group (exposure) and 99 patients in the without BBB disruption group (control). Multiple logistic regression analysis revealed a significantly increased risk of SAP in patients with BBB disruption (OR = 2.337, 95% CI: 1.118-4.990, p = 0.025). Furthermore, mediation analysis suggested that this association may be partly due to malignant cerebral oedema and haemorrhagic transformation. The study found an inverse L-shaped dose-response relationship between the maximum CT values of BBB disruption areas and the incidence of SAP. SAP partially mediated the association between BBB disruption and 3-month poor functional outcome. Conclusion: BBB disruption are a potential risk factor for SAP. BBB disruption may affect short- and medium-term prognosis of patients after ET in part through SAP.

Predicting 3-month Functional Outcome After Endovascular Thrombectomy in Patients with Anterior Circulation Occlusion with an Arterial Transit Artifact Grading System.

PURPOSE: The objective of this study was to evaluate the relationship between arterial transit artifact (ATA), arterial spin labeling (ASL) perfusion imaging, and the outcome of patients with acute ischemic stroke (AIS) due to occlusion of large vessels in anterior circulation after endovascular thrombectomy (EVT). METHODS: Patients with anterior circulation occlusion treated with EVT between October 2017 and December 2021 were enrolled in this retrospective study, and ATA was quantified by a 4-point scale. A favorable outcome was defined by modified Rankin Scale (mRS) scores of 0-2 at 3 months. To identify independent predictors of favorable outcome, age, sex, risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) score, site of occlusion, cause of stroke, and early reperfusion were evaluated with univariate and multivariate analyses. Predictive accuracy was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC) for the model. RESULTS: In this study 187 patients (age, 65.0 ± 12.5 years; men, 55%) were evaluated. Younger age (odds ratio, OR, 0.95; 95% confidence interval, CI, 0.92-0.98, p = 0.002), lower baseline NIHSS score (OR, 0.88; 95% CI, 0.82-0.94, p < 0.001), and lower ATA score (OR, 1.14; 95% CI, 1.06-1.22, p < 0.001) were independently associated with favorable outcomes in multivariate analysis. The ATA score has moderate to good accuracy in predicting favorable outcomes (AUC, 0.753). CONCLUSION: A high ATA score as a potential predictor, can help identify patients who may benefit from EVT.

Endovascular thrombectomy versus medical management on outcomes with infarct volumes more than 70 mL.

OBJECTIVE: Endovascular thrombectomy (EVT) in patients with large infarct volume remains controversial. The aim of this study is to compare clinical outcomes between EVT and medical management in acute large vessel occlusion with infarct volumes larger than 70 mL on diffusion-weighted magnetic resonance imaging (DWI). METHODS: A prospective observational cohort study was conducted, including patients with anterior cerebral circulation occlusion due to ischemic stroke with infarct volumes larger than 70 mL within 24 h of onset between July 2018 and June 2023. Eligible patients were divided into two groups: the EVT group and the medical management (non-EVT) group. The main outcomes were functional independence and mortality at 90 days. To assess clinical endpoints, we selected variables including age, NIHSS score, infarct volume, and occlusion location for 1:1 propensity score (PS) matching and PS adjustment using inverse probability of treatment weighting (IPTW). RESULTS: Among the 131 identified patients (mean [SD] age, 69.9 [13.7] years; 58 female), the median infarct volume was 123.6 mL. Of these patients, 75 (57.3%) underwent EVT. After PS adjustment, EVT was not associated with functional independence (10.9% vs. 10.9%; p = 1.000) or mortality (43.5% vs. 47.8%; p = 0.675). Additionally, after PS adjustment using IPTW, EVT was also not associated with a functional independence (15.8% vs. 13.7%; p = 0.767) or mortality (46.8% vs. 44.0%; p = 0.762). CONCLUSION: This study provides real-world evidence regarding infarct volumes larger than 70 mL, indicating that EVT does not provide benefits compared to medical management alone when considering age, NIHSS score, infarct volume, and occlusion location.

HMGB1, angel or devil, in ischemic stroke.

INTRODUCTION: High-mobility group box 1 protein (HMGB1) is extensively involved in causing ischemic stroke, pathological damage of ischemic brain injury, and neural tissue repair after ischemic brain injury. However, the precise role of HMGB1 in ischemic stroke remains to be elucidated. METHODS: Comprehensive literature search and narrative review to summarize the current field of HMGB1 in cerebral ischemic based on the basic structure, structural modification, and functional roles of HMGB1 described in the literature. RESULTS: Studies have exhibited the crucial roles of HMGB1 in cell death, immunity and inflammation, thrombosis, and remodeling and repair. HMGB1 released after cerebral infarction is extensively involved in the pathological injury process in the early stage of cerebral infarction, whereas it is involved in the promotion of brain tissue repair and remodeling in the late stage of cerebral infarction. HMGB1 plays a neurotrophic role in acute white matter stroke, whereas it causes sustained activation of inflammation and plays a damaging role in chronic white matter ischemia. CONCLUSIONS: HMGB1 plays a complex role in cerebral infarction, which is related to not only the modification of HMGB1 and bound receptors but also different stages and subtypes of cerebral infarction. future studies on HMGB1 should investigate the spatial and temporal dynamics of HMGB1 after cerebral infarction. Moreover, future studies on HMGB1 should attempt to integrate different stages and infarct subtypes of cerebral infarction.

A potential relationship between MMP-9 rs2250889 and ischemic stroke susceptibility.

Purpose: Ischemic stroke (IS), a serious cerebrovascular disease, greatly affects people's health and life. Genetic factors are indispensable for the occurrence of IS. As a biomarker for IS, the MMP-9 gene is widely involved in the pathophysiological process of IS. This study attempts to find out the relationship between MMP-9 polymorphisms and IS susceptibility. Methods: A total of 700 IS patients and 700 healthy controls were recruited. The single nucleotide polymorphism (SNP) markers of the MMP-9 gene were genotyped by the MassARRAY analyzer. Multifactor dimensionality reduction (MDR) was applied to generate SNP-SNP interaction. Furthermore, the relationship between genetic variations (allele and genotype) of the MMP-9 gene and IS susceptibility was analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Results: Our results demonstrated that rs2250889 could significantly increase the susceptibility to IS in the codominant, dominant, overdominant, and log-additive models (p < 0.05). Further stratification analysis showed that compared with the control group, rs2250889 was associated with IS risk in different case groups (age, female, smoking, and non-drinking) (p < 0.05). Based on MDR analysis, rs2250889 was the best model for predicting IS risk (cross-validation consistency: 10/10, OR = 1.56 (1.26-1.94), p < 0.001). Conclusion: Our study preliminarily confirmed that SNP rs2250889 was significantly associated with susceptibility to IS.

The Functional Prognosis of Rescue Conscious Sedation During Mechanical Thrombectomy on Patients with Acute Anterior Circulation Ischemic Stroke: A Single-Center Retrospective Study.

INTRODUCTION: Based on real-world case data, this study intends to explore and analyze the impact of rescue conscious sedation (CS) on the clinical outcomes of patients with anterior circulation acute ischemic stroke (AIS) receiving mechanical thrombectomy (MT). METHODS: This retrospective study enrolled patients with anterior circulation AIS who received MT and were treated with either single local anesthesia (LA) or rescue CS during MT between January 2018 and October 2021. We used univariate and multivariate logistic regression methods to compare the impact of LA and CS on the clinical outcomes of patients with AIS who received MT, including the mRS at 90 days, the incidence of poststroke pneumonia (PSP), the incidence of symptomatic intracranial cerebral hemorrhage (sICH), and the mortality rate. RESULTS: We reviewed 314 patient cases with AIS who received MT. Of all patients, 164 met our search criteria. Eighty-nine patients received LA, and 75 patients received rescue CS. There was no significant difference between the two groups in the 90-day good prognosis (45.3% vs. 51.7%, p = 0.418) and mortality (17.3% vs. 22.5%, p = 0.414). Compared with the LA group, the incidence of postoperative pneumonia in the rescue CS group (44% vs. 25.8%, p = 0.015) was more significant. Multivariate stepwise logistic regression analysis revealed that intraoperative remedial CS was independently associated with PSP following MT. In a subgroup analysis, rescue CS was found to significantly increase the incidence of PSP in patients with dysphagia (OR = 7.307, 95% CI 2.144-24.906, p = 0.001). As the severity of the National Institutes of Health Stroke Scale (NIHSS) increased, intraoperative rescue CS was found to increase the risk of PSP (OR = 1.155, 95% CI 1.034-1.290, p = 0.011) by 5.1% compared to that of LA (OR = 1.104, 95% CI 1.013-1.204, p = 0.024). CONCLUSION: Compared to LA, rescue CS during MT does not significantly improve the 90 days of good prognosis and reduce the incidence of sICH and mortality in patients with anterior circulation AIS. However, it has a significantly increased risk of poststroke pneumonia (PSP), particularly in patients with dysphagia.

Nomogram to predict unfavorable outcome of endovascular thrombectomy for large ischemic core.

OBJECTIVE: The prognosis for patients presenting with a large ischemic core (LIC) following endovascular thrombectomy is relatively poor. This study aimed to construct and validate a nomogram for predicting 3-month unfavorable outcome in patients with anterior circulation occlusion-related LIC who underwent endovascular thrombectomy. METHODS: A retrospective training cohort and a prospective validation cohort of patients with a large ischemic core were studied. The diffusion weighted imaging related radiomic features and pre-thrombectomy clinical features were collected. After the selection of relevant features, a nomogram predicting modified Rankin Scale score of 3-6 as an unfavorable outcome was established. The discriminatory value of the nomogram was evaluated with a receiver operating characteristic curve. RESULTS: A total of 140 patients (mean age 66.3 ± 13.4 years, 35% female) were included in this study, consisting of a training cohort (n = 95) and a validation cohort (n = 45). The percentage of patients with an mRS scores of 0-2 was 30%, 0-3 was 40.7%, and 32.9% were dead. Age, National Institute of Health Stroke Scale (NIHSS) score, and two radiomic features, Maximum2DDiameterColumn and Maximum2DDiameterSlice, were identified as factors associated with unfavorable outcome in the nomogram. The nomogram demonstrated an area under the curve of 0.892 (95% confidence interval [CI], 0.812-0.947) in the training dataset and 0.872 (95% CI, 0.739-0.953) in the validation dataset. INTERPRETATION: This nomogram, which includes age, NIHSS score, Maximum2DDiameterColumn, and Maximum2DDiameterSlice, may predict the risk of unfavorable outcome in patients with LIC caused by anterior circulation occlusion.

The relationship between vertebrobasilar artery calcification and intracranial atherosclerosis-related occlusion in thrombectomy.

Background and purpose: Distinguishing between intracranial atherosclerosis-related occlusion (ICAS-O) and non-ICAS-O can benefit strategies of identifying the need for surgical plans prior to thrombectomy. We investigated the association between vertebrobasilar artery calcification (VBAC) and ICAS-O in acute ischemic stroke patients undergoing thrombectomy. Methods: Patients were recruited from a prospective single-center registration study who had undergone thrombectomy between October 2017 and October 2021. The enrolled patients were divided into ICAS-O and non-ICAS-O, as determined by the intraarterial therapy process. The occurrences of VBAC were recorded on intracranial non-contrast computed tomography (NCCT) scans before thrombectomy. The association between VBAC and ICAS-O was assessed using binary logistic regression. Results: A total of 2732 patients who had undergone digital subtraction angiography were reviewed, and 314 thrombectomy patients (mean age: 65.4 years, 36.6% female) with NCCT were enrolled in this study. VBAC was detected before thrombectomy in 113 (36%) out of 314 patients. Age, hypertension, and diabetes were associated with VBAC, and a higher frequency of VBAC was identified in patients presenting posterior circulation. ICAS-O accounts for 43% (135/314) in eligible patients. From multivariable analyses, VBAC was identified as an independent predictor of ICAS-O (adjusted odds ratio, 6.16 [95% CI, 2.673-14.217], P < 0.001). Meanwhile, the (VBAC[+] atrial fibrillation[-]) group displayed higher rates of ICAS-O than the (VBAC[-] atrial fibrillation [-]) group (P < 0.001). Conclusions: We demonstrated that VBAC is an independent risk factor for ICAS-O in patients who underwent thrombectomy. Patients free of atrial fibrillation with VBAC have more trend to be ICAS-O.

Impact of Body Temperature in Patients With Acute Basilar Artery Occlusion: Analysis of the BASILAR Database.

Background: A link between body temperature and stroke outcomes has been established but not for acute basilar artery occlusion. We aimed to determine the association between body temperature and clinical outcomes in patients with acute basilar artery occlusion and temperature management range. Methods: We included patients from the Endovascular Treatment for Acute Basilar Artery Occlusion Study (BASILAR) database with records of both admission body temperature (ABT) and peak body temperature (PBT). ABT was defined as the body temperature first measured at the hospital visit, PBT was defined as the highest temperature within 24 h of treatment, and minus body temperature (MBT) was defined as PBT-ABT. The primary clinical outcome was favorable functional outcome, defined as the proportion of patients with a modified Rankin Scale score of 0-3 at 3 months. Secondary outcomes included 3-month mortality, in-hospital mortality, and symptomatic cerebral hemorrhage. Results: A total of 664 patients were enrolled in the study; 74.7% were men, with a median age of 65 (interquartile range, 57.25-74) years. In all patients, multivariate analysis indicated that PBT and MBT were independent predictors of favorable functional outcome [odds ratio (OR), 0.57 (95% CI, 0.43-0.77); OR, 0.68 (95% CI, 0.52-0.88), respectively], and higher ABT, PBT, and MBT were associated with an increased 3-month mortality [OR, 1.47 (95% CI, 1.03-2.10), OR, 1.58 (95% CI, 1.28-1.96), OR, 1.35 (95% CI, 1.11-1.65), respectively]. Proportional odds models demonstrated that when ABT, PBT, MBT were in the range of <37.5, <38.9, and -0.6-2.7°C, respectively, the benefit of the endovascular treatment is clearly greater than that of standard medical treatment in terms of favorable functional outcome. Conclusions: Body temperature is an independent predictor of clinical outcome in patients with acute basilar artery occlusion. It is necessary to control the patient body temperature within the appropriate range in clinical settings. Trial Registration: Chinese Clinical Trial Registry ChiCTR1800014759. Registered 03 February 2018. Retrospectively registered.

Hyperattenuated Lesions on Immediate Non-contrast CT After Endovascular Therapy Predict Intracranial Hemorrhage in Patients With Acute Ischemic Stroke: A Retrospective Propensity Matched Study.

Background and Purpose: This study aimed to analyze the association between hyperattenuated lesions (HALs) and postoperative intracranial hemorrhage (IH) and predict perioperative IH through quantitative analysis of HALs in acute ischemic stroke (AIS) with anterior large vessel occlusion (LVO) after endovascular therapy (ET). Materials and Methods: This retrospective, propensity-matched study enrolled AIS who received ET from a single-center registry study between August 2017 and May 2020. The enrolled patients were divided into two groups: IH and non-IH, by follow-up postoperative CT. The occurrences of HALs on immediate CT after ET were also recorded. The association between IH and HALs after propensity score matching (PSM) was determined by binary logistic regression models. The receiver operating characteristic (ROC) curve was used to determine the predictive value of the highest CT Hounsfield units (HU) value on immediate CT. Results: Initially, 1,418 patients who underwent digital subtraction angiography were reviewed and 114 AIS patients with immediate postoperative CT and follow-up CT after ET were enrolled. Forty-nine out of the 114 patients developed IH after therapy. After PSM analysis, patients with IH were more likely to have HALs on immediate CT (Odds Ratio, OR 11.9, P = 0.002, and 95% CI: 2.485-57.284). For 80 patients with HALs, ROC analysis of the highest CT value in the HALs territory showed that the cut-off value was 97 HU, the sensitivity was 70.21%, and the specificity was 81.82%. Conclusions: Patients with HALs after ET are more likely to have perioperative IH. The highest CT value in the HALs area might be used to predict IH.

Protective effects of ginsenoside Rb1 on H2O2-induced oxidative injury in human endothelial cell line (EA.hy926) via miR-210.

Ginsenoside Rb1 (Rb1) possesses a cardioprotective effect via mediating microRNAs (miRs), while it is unexplored whether miR-210 is regulated by Rb1 in response to oxidative stress. Human endothelial EA.hy926 cells were stimulated with H2O2 before Rb1 treatment. After transfection, cell viability, apoptosis, migration, and invasion assays were conducted. Western blot was applied to quantify protein. BCL2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) and miR-210 were analyzed with quantitative reverse transcription polymerase chain reaction. Dual luciferase activity assay was performed. Rb1 elevated viability, migration, and invasion of H2O2-treated cells. H2O2-induced apoptosis was moderated by Rb1. miR-210 was augmented in H2O2-treated cells after Rb1 stimulation. miR-210 inhibitor abolished the positive effects of Rb1. BNIP3 was negatively modulated by miR-210 and implicated in modulating viability, apoptosis, and migration and invasion. In addition, BNIP3 modulated phosphorylation of regulators. Rb1 repressed oxidative injury via elevating miR-210. miR-210 negatively mediated BNIP3, which participated in oxidative damage via regulating mammalian targets of rapamycin (mTOR) and nuclear factor-κB (NF-κB).

MicroRNA-769-5p Promotes The Growth Of Glioma Cells By Targeting Lysine Methyltransferase 2A.

BACKGROUND: Accumulating evidence supports the involvement of microRNAs (miRNAs) in the progression of human cancers including glioma. Recently, miR-769-5p has been reported to play a tumor suppressive role in colorectal cancer and lung cancer, whereas it exerts an oncogenic role in melanoma. However, the role of miR-769-5p and its related mechanism are poorly elucidated. METHODS: The levels of miR-769-5p in glioma tissues and adjacent non-tumor tissues were detected by qRT-PCR. In addition, the effects of miR-769-5p on cell proliferation and apoptosis were evaluated by CCK-8, EdU, colony formation and flow cytometric assays, respectively. Meanwhile, the dual-luciferase reporter assay was used to investigate the interaction of miR-769-5p and lysine methyltransferase 2A (KMT2A) in glioma. RESULTS: We found that miR-769-5p expression was strongly upregulated in glioma tissues and cell lines. Glioma tissues with high World Health Organization (WHO) grades had obvious higher levels of miR-769-5p compared to samples with low WHO grades. Interestingly, glioma patients highly expressing miR-769-5p showed prominent poorer survivals. Knockdown of miR-769-5p significantly suppressed cell proliferation and resulted in apoptosis in glioma cells. Additionally, miR-769-5p silencing restrained in vivo growth of glioma cells in mice. Interestingly, KMT2A was identified to be a direct target of miR-769-5p in glioma cells. The expression of KMT2A mRNA was downregulated in glioma tissues and inversely correlated with miR-769-5p level. KMT2A overexpression inhibited cell proliferation and induced the apoptosis of A172 cells. Moreover, siRNA-mediated KMT2A silencing could partially abolish miR-769-5p knockdown-induced suppressive effects on A172 cells. CONCLUSION: In summary, our findings suggest that targeting miR-769-5p/KMT2A axis may be a promising therapeutic target for glioma treatment.