Prognostic value of angiographic based quantitative flow ratio and anatomic features in intracranial atherosclerotic stenosis.

BACKGROUND: Patients with intracranial atherosclerotic stenosis (ICAS) are prone to stroke recurrence despite aggressive medical treatment. Further assessment of the anatomy and physiology of ICAS is urgently needed to facilitate individualized therapy. We explored the predictive value of angiography based hemodynamic and anatomical features for ICAS patients. METHODS: In this retrospective study, patients with moderate-to-severe stenosis of the middle cerebral artery (MCA) were enrolled. The hemodynamic assessment was performed using the single view Murray's law based quantitative flow ratio (µQFR) approach. The locations of lesions were categorized as perforator rich segments of the MCA (pMCA) and others. Multivariate Cox models were developed to identify significant predictors. The primary outcomes were defined as stroke and transient ischemic attack. RESULTS: Among the 333 patients (median (IQR) age, 56 (49-63) years, 70.3% men) over a median follow-up period of 64.5 months, 50 (15.0%) had the primary outcomes, and 80.0% occurred within 5 years. Patients with lower µQFR values (dichotomized at 0.73) had a higher risk of the 5 year primary outcomes (log rank P=0.023), and good collateral circulation may have attenuated the risk. In the multivariate analyses, µQFR (adjusted HR=0.345; 95% CI 0.155 to 0.766; P=0.009), lesion located in pMCA (adjusted HR=0.377; 95% CI 0.190 to 0.749; P=0.005), and diameter ratio of the internal carotid artery (adjusted HR=4.187; 95% CI 1.071 to 16.370; P=0.040) were significantly associated with the 5 year primary outcomes. CONCLUSIONS: Angiography based µQFR and anatomical features, namely plaque localization and internal carotid artery expansion, could serve as promising prognostic indexes for MCA atherosclerosis.

Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury.

BACKGROUND: Neuroinflammation is a vital pathophysiological process during ischemic stroke. Activated astrocytes play a major role in inflammation. Lipocalin-2 (LCN2), secreted by activated astrocytes, promotes neuroinflammation. Pyroptosis is a pro-inflammatory form of programmed cell death that has emerged as a new area of research in stroke. Nevertheless, the potential role of LCN2 in astrocyte pyroptosis remains unclear. METHODS: An ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in vivo. In this study, in vitro, oxygen-glucose deprivation and reoxygenation (O/R) were applied to cultured astrocytes. 24p3R (the LCN2 receptor) was inhibited by astrocyte-specific adeno-associated virus (AAV-GFAP-24p3Ri). MCC950 and Nigericin sodium salt (Nig) were used to inhibit or promote the activation of NLRP3 inflammasome pharmacologically, respectively. Histological and biochemical analyses were performed to assess astrocyte and neuron death. Additionally, the neurological deficits of mice were evaluated. RESULTS: LCN2 expression was significantly induced in astrocytes 24 h after stroke onset in the mouse MCAO model. Lcn2 knockout (Lcn2-/-) mice exhibited reduced infarct volume and improved neurological and cognitive functions after MCAO. LCN2 and its receptor 24p3R were colocalized in astrocytes. Mechanistically, suppression of 24p3R by AAV-GFAP-24p3Ri alleviated pyroptosis-related pore formation and the secretion of pro-inflammatory cytokines via LCN2, which was then reversed by Nig-induced NLRP3 inflammasome activation. Astrocyte pyroptosis was exacerbated in Lcn2-/- mice by intracerebroventricular administration of recombinant LCN2 (rLCN2), while this aggravation was restricted by blocking 24p3R or inhibiting NLRP3 inflammasome activation with MCC950. CONCLUSION: LCN2/24p3R mediates astrocyte pyroptosis via NLRP3 inflammasome activation following cerebral ischemia/reperfusion injury.

Genetically Predicted Sleep Traits and Functional Outcome After Ischemic Stroke: A Mendelian Randomization Study.

BACKGROUND AND OBJECTIVES: Sleep traits can have implications for ischemic stroke recovery in observational studies. The purpose of our present study was to explore the relationship between genetically predicted sleep traits and poststroke functional outcomes with Mendelian randomization (MR) method. METHODS: Instrumental variables for insomnia and sleep duration were adopted from genome-wide association studies data of European ancestry individuals. Summary data for functional outcome after ischemic stroke were retrieved from the Genetics of Ischemic Stroke Functional Outcome network. Inverse-variance weighted approach was adopted as the main analyses. Alternative MR approaches were used in sensitivity analyses. I2 and Q value statistics were used to appraise the heterogeneity among genetic variants. RESULTS: In univariable analysis, genetic liability to insomnia was significantly associated with worse functional outcome (modified Rankin Scale ≥3) after ischemic stroke (odds ratio [OR] = 1.30; 95% CI: 1.10-1.54, p = 0.002). Genetic liability to short sleep, long sleep, and continuous sleep duration were not associated with poststroke functional outcome (all p > 0.05). Sensitivity analyses without adjustment for stroke severity also supported that insomnia was causally associated with poor functional outcome (OR = 1.25; 95% CI: 1.08-1.44, p = 0.003). In the multivariable MR analysis adjusting for potentially confounding traits including body mass index, depression, type 2 diabetes, smoking, and alcohol consumption, the overall patterns between genetic liability to insomnia and poststroke outcome remained (all p < 0.05). DISCUSSION: This MR study supports potential adverse effects of liability to insomnia on functional outcome after ischemic stroke. Interventions that address insomnia may offer a therapeutic target to improve recovery after ischemic stroke and warrant exploration in a clinical context.

Optical Coherence Tomography Evaluation of Carotid Artery Stenosis and Stenting in Patients With Previous Cervical Radiotherapy.

Objectives: Cervical radiotherapy can lead to accelerated carotid artery stenosis, increased incidence of stroke, and a higher rate of in-stent restenosis in irradiated patients. Our objective was to reveal the morphological characteristics of radiation-induced carotid stenosis (RICS) and the stent-vessel interactions in patients with previous cervical radiotherapy by optical coherence tomography (OCT). Materials and Methods: Between November 2017 and March 2019, five patients with a history of cervical radiotherapy were diagnosed with severe carotid artery stenosis and underwent carotid artery stenting (CAS). OCT was conducted before and immediately after the carotid stent implantation. Two patients received OCT evaluation of carotid stenting at 6- or 13-month follow-up. Results: The tumor types indicating cervical radiotherapy were nasopharyngeal carcinoma (n = 3), cervical esophageal carcinoma (n = 1), and cervical lymphoma (n = 1). The median interval from the radiotherapy to the diagnosis of RICS was 8 years (range 4-36 years). Lesion characteristics of RICS were detected with heterogeneous signal-rich tissue, dissection, and advanced atherosclerosis upon OCT evaluation. Post-interventional OCT revealed 18.2-57.1% tissue protrusion and 3.3-13.8% stent strut malapposition. Follow-up OCT detected homogeneous signal-rich neointima and signal-poor regions around stent struts. In the patient with high rates of tissue protrusion and stent strut malapposition, the 6-month neointima burden reached 48.9% and microvessels were detected. Conclusion: The morphological features of RICS were heterogeneous, including heterogeneous signal-rich tissue, dissection, and advanced atherosclerosis. Stenting was successful in all 5 patients with severe RICS. One patient, with high rates of tissue protrusion and stent strut malapposition immediately after stenting, received in-stent neointimal hyperplasia at a 6-month follow-up.

Review of net water uptake in the management of acute ischemic stroke.

CT densitometry-based methods to directly quantify net water uptake in ischemic brain tissue have been increasingly applied recently. There is potential for net water uptake to be used as an imaging biomarker for the pathophysiology of infarcted lesions. This review is aimed at summarizing the potential and current status of the application of net water uptake as a biomarker in the management of ischemic stroke and future directions in this context. Specifically, we provide a brief overview of the principle and different methods of net water uptake measurement, followed by a discussion of the role of net water uptake in predicting malignant brain edema and hemorrhagic transformation, evaluating lesion age, and predicting the efficacy of reperfusion therapy and long-term clinical prognosis. Artificial intelligence will help address the lack of automation and standardization in the measurement of net water absorption. Further validation of net water uptake in a prospective multicenter setting is necessary. KEY POINTS: • NWU can be used as a quantitative imaging biomarker for developing malignant brain edema in anterior and posterior circulation strokes. • The difference in NWU in edema arrest or reversibility suggests that rapid and successful revascularization can influence the progression of ischemic edema. • NWU can be used to predict the age of a lesion, with predictive power comparable to that of DWI/FLAIR mismatch.

Astrocytic phagocytosis contributes to demyelination after focal cortical ischemia in mice.

Ischemic stroke can cause secondary myelin damage in the white matter distal to the primary injury site. The contribution of astrocytes during secondary demyelination and the underlying mechanisms are unclear. Here, using a mouse of distal middle cerebral artery occlusion, we show that lipocalin-2 (LCN2), enriched in reactive astrocytes, expression increases in nonischemic areas of the corpus callosum upon injury. LCN2-expressing astrocytes acquire a phagocytic phenotype and are able to uptake myelin. Myelin removal is impaired in Lcn2-/- astrocytes. Inducing re-expression of truncated LCN2(Δ2-20) in astrocytes restores phagocytosis and leads to progressive demyelination in Lcn2-/- mice. Co-immunoprecipitation experiments show that LCN2 binds to low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes. Knockdown of Lrp1 reduces LCN2-induced myelin engulfment by astrocytes and reduces demyelination. Altogether, our findings suggest that LCN2/LRP1 regulates astrocyte-mediated myelin phagocytosis in a mouse model of ischemic stroke.

Automated quantitative lesion water uptake in acute stroke is a predictor of malignant cerebral edema.

OBJECTIVES: Net water uptake (NWU) has been shown to have a linear relationship with brain edema. Based on an automated-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) technique, we automatically derived NWU from baseline multimodal computed tomography (CT), namely ASPECTS-NWU. We aimed to determine if ASPECTS-NWU can predict the development of malignant cerebral edema (MCE). METHODS: One hundred and forty-six patients with large-vessel occlusion were retrospectively enrolled. Quantitative NWU based on automated-ASPECTS was measured both on nonenhanced CT (NECT) and CT angiography (CTA), namely NECT-ASPECT-NWU and CTA-ASPECTS-NWU. The correlation between ASPECTS-NWU and cerebral edema (CED) grades was calculated using Spearman rank correlation. Univariate logistic regression was used to assess the effect of radiological and clinical features on MCE, and a multivariable model with significant factors from the univariate regression analysis was built. Receiver operating characteristic (ROC) was obtained and area under curve (AUC) was compared. RESULTS: CTA-ASPECTS-NWU had a moderate positive correlation with CED grades (r = 0.62; 95% confidence interval [CI], 0.51-0.71; p < 0.001). The CTA-ASPECTS-NWU performed better than the NECT-ASPECTS-NWU with AUC: 0.88 vs. 0.71 (p < 0.001). Multivariable logistic regression model integrating CTA-ASPECTS-NWU, collateral score, and age showed the CTA-ASPECTS-NWU was an independent predictor of MCE with an AUC of 0.94 (95% CI: 0.90-0.98; p < 0.001). CONCLUSIONS: This study demonstrates that ASPECTS-NWU is a quantitative predictor of MCE after large-vessel occlusion of the middle cerebral artery territory. The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment. KEY POINTS: • The automated-ASPECTS technique can automatically detect the affected regions with early ischemic changes and NWU could be manually calculated. • The CTA-ASPECTS-NWU performs better than the NECT-ASPECTS-NWU on predicting the development of MCE. • The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment.

Influence of renal impairment on clinical outcomes after endovascular recanalization in vertebrobasilar artery occlusions.

BACKGROUND: Renal impairment (RI) is associated with worse outcomes in the treatment of intravenous thrombolysis and emergent endovascular treatment (EVT) in anterior circulation stroke. The objective of this study was to investigate the association of RI with short-term and long-term outcomes in patients with vertebrobasilar artery occlusions (VBAO) who received EVT. METHODS: Consecutive patients with VBAO receiving EVT involving 21 stroke centers were retrospectively included. Multivariate regression analyses were used to evaluate the association of RI with mortality and symptomatic intracranial hemorrhage (sICH) during the hospital stay, and also mortality, favorable functional outcome (modified Rankin Scale (mRS) score of 0-3), and functional improvement (shift in mRS score) at 3 months and 1 year follow-up. The association between RI and the risk of recurrent stroke was evaluated with multivariate competing-risk regression analyses. RESULTS: After adjustment for potential confounders, RI was independently associated with sICH (OR 3.30, 95% CI 1.55 to 7.18), as well as mortality (OR 2.54, 95% CI 1.47 to 4.38; OR 3.07, 95% CI 1.72 to 8.08), favorable functional outcome (OR 0.33, 95% CI 0.17 to 0.66; OR 0.25, 95% CI 0.12 to 0.51), and functional improvement (OR 0.45, 95% CI 0.28 to 0.74; OR 0.35, 95% CI 0.21 to 0.60) at 3 months and 1 year follow-up, respectively, but RI was not associated with in-hospital mortality. Additionally, there was no significant association between RI and recurrent stroke within 1 year. CONCLUSIONS: Our findings suggest that RI is associated with a higher risk of sICH in hospital and a decrease in survival, favorable functional outcome, and functional improvement at 90 days and 1 year follow-up. TRIAL REGISTRATION NUMBER: URL: http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.

CD99 mediates neutrophil transmigration through the bEnd.3 monolayer via the induction of oxygen-glucose deprivation.

AIM/BACKGROUND: CD99 participate in neutrophil infiltration after inflammatory events; however, despite the important role of inflammation in ischemic stroke, the role of CD99 in ischemic stroke remains unclear. METHOD: In the present study, we detected the protein expression of CD99, ICAM-1, and CD31 (PECAM-1) in oxygen-glucose deprivation (OGD)-induced bEnd.3 cells and neutrophils and explored the influence of HIF-1α and IL-1ß on their expression. We also explored the role of CD99 in the OGD-induced transmigration of neutrophils. RESULTS: Our results showed that OGD induction upregulated CD99 in bEnd.3 cells and that this effect could be abolished by the preadministration of IL-1ß and was not mediated by HIF-1α. However, the activation of ICAM-1 by OGD remained activated with IL-1ß treatment. No significant influence of IL-1ß on OGD-induced CD31. Finally, we found a significant increase in infiltrated neutrophils after OGD induction compared with the control and OGD + anti-CD99 groups. CONCLUSION: Our results indicated that CD99 mediates neutrophil infiltration and transmigration via OGD induction and thus constitutes a potential therapeutic target for anti-inflammatory treatment after ischemic stroke.

Endovascular Treatment of Cerebral Venous Sinus Stenosis Based on Hemodynamic Assessment Using Pressure Wire.

BACKGROUND: A pressure wire offers a dynamic tool to assist in the measurement of the pressure gradient and assessment of the functional significance of stenosis. The author presents a patient with idiopathic intracranial hypertension who was diagnosed with cerebral venous sinus stenosis (CVSS). Venography accompanied by pressure measurement was used to guide the stent placement for CVSS. CASE DESCRIPTION: A 27-year-old woman was referred to our hospital with a chief complaint of headache and neckache lasting for 7 weeks, with an 8-day history of binocular diplopia and blurred vision. Magnetic resonance venography and digital subtraction angiography showed a filling defect in the right transverse sinus. A pressure wire was used before endovascular treatment and showed that the pressure gradient was 10 mm Hg, which meets the surgical indication. After a stent was placed, no pressure gradient was recorded by the pressure wire. CONCLUSIONS: This is the first report about using a pressure wire for CVSS. The finding suggests that use of a pressure wire can be a new approach in the diagnosis and treatment of CVSS.

Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway.

Astrocytes, the most numerous cells in the human brain, play a central role in the metabolic homeostasis following hypoxic injury. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, has been shown to converge prosurvival signaling in the central nerve system. The present study aimed to investigate the role of Cav-1 in the hypoxia-induced astrocyte injury. We also examined how Cav-1 alleviates apoptotic astrocyte death. To this end, primary astrocytes were exposed to oxygen-glucose deprivation (OGD) for 6 h and a subsequent 24-h reoxygenation to mimic hypoxic injury. OGD significantly reduced Cav-1 expression. Downregulation of Cav-1 using Cav-1 small interfering RNA dramatically worsened astrocyte cell damage and impaired cellular glutamate uptake after OGD, whereas overexpression of Cav-1 with Cav-1 scaffolding domain peptide attenuated OGD-induced cell apoptosis. Mechanistically, the expressions of Ras-GTP, phospho-Raf, and phospho-ERK were sequestered in Cav-1 small interfering RNA-treated astrocytes, yet were stimulated after supplementation with caveolin peptide. MEK/ERK inhibitor U0126 remarkably blocked the Cav-1-induced counteraction against apoptosis following hypoxia, indicating Ras/Raf/ERK pathway is required for the Cav-1's prosurvival role. Together, these findings support Cav-1 as a checkpoint for the in hypoxia-induced astrocyte apoptosis and warrant further studies targeting Cav-1 to treat hypoxic-ischemic brain injury.

Hypertension unawareness among Chinese patients with first-ever stroke.

BACKGROUND: The low rates of hypertension treatment and control, partly due to its unawareness, are the main causes of the high stroke incidence in China. The purpose of this study was to evaluate hypertension unawareness amongst patients with first-ever stroke and to detect factors associated with its unawareness. METHODS: We selected those diagnosed with hypertension from patients with first-ever stroke registered in the Nanjing Stroke Registry Program between 2004 and 2014. These hypertensives were divided as being aware or unaware of their hypertension by using a brief questionnaire conducted shortly after the stroke. Multivariate logistic regression analysis was performed to identify potential factors associated with hypertension unawareness. RESULTS: Of the 5309 patients with first-ever stroke, 3732 (70.3%) were diagnosed with hypertension. Among which, 593 (15.9%) were unaware of their hypertension at the time of stroke onset. Lower-level of education (primary school or illiteracy) and smoking were associated positively with hypertension unawareness; while advanced age, overweight, diabetes mellitus, heart diseases and family history of stroke were associated negatively with hypertension unawareness. Annual data analyzed indicated that the rate of hypertension awareness increased during the past 11 years (r = 0.613, P = 0.045 for trends). CONCLUSIONS: A substantial proportion (15.9%) of Chinese patients with hypertension had not been aware of this covert risk until an overt stroke occurred. Hypertension unawareness was associated with lower educational levels and smoking, which address the importance of health education especially in these individuals.

Impacts and interactions of PDGFRB, MMP-3, TIMP-2, and RNF213 polymorphisms on the risk of Moyamoya disease in Han Chinese human subjects.

Polymorphisms of PDGFRB, MMP-3, TIMP-2, RNF213, TGFB1, Raptor and eNOS genes have been associated with Moyamoya disease (MMD) separately in studies, but their interactions on MMD have never been evaluated in one study. This study enrolled 96 MMD patients and 96 controls to evaluate the contributions and interactions of these polymorphisms on MMD in Chinese Hans. After genotyping, five polymorphisms loci were deemed suitable for analysis, rs3828610 in PDGFRB, rs3025058 in MMP-3, rs8179090 in TIMP-2, rs112735431 and rs148731719 in RNF213. Interactions of different loci on MMD were evaluated by multifactor dimensionality reduction (MDR) method. Significantly higher frequencies of A allele and G/A genotype of rs112735431 in RNF213 were observed in MMD patients compared with controls (P=0.011; P=0.018, respectively). In the dominant model, G/A genotype of rs112735431 was associated with increased risk of MMD (P=0.018). A higher frequency of G allele and G/G genotype of rs148731719 in RNF213 gene in patient than control group (P<0.001; P<0.01, respectively) was also detected. No significant association between MMD and other three loci (P>0.05) was detected. MDR analysis failed to detect any significant interaction among these five loci in the occurrence of MMD (P>0.05), but the combination of three loci (rs112735431 in RNF213, rs3828610 in PDGFRB, rs3025058 in MMP-3) could have the maximum testing accuracy (57.29%) and cross-validation consistency (10/10). The results indicated that RNF213 rs112735431 and rs148731719 may exert a significant influence on MMD occurrence. Compared with this overwhelming effect, the influences of PDGFRB, MMP-3, and TIMP-2 on MMD may be unremarkable in Chinese Hans. There may be no prominent interaction among these five gene polymorphisms on the occurrence of MMD.

Feasibility of delivering mesenchymal stem cells via catheter to the proximal end of the lesion artery in patients with stroke in the territory of the middle cerebral artery.

Stem cell-based therapy shows great potential in stroke patients. Intra-artery infusion exhibits greater biological distribution compared to intravenous delivery. In addition, umbilical cord mesenchymal stem cells (UCMSCs) have several advantages compared with other types of stem cells. The aim of this study was to evaluate the safety and efficacy of UCMSCs delivered by a catheter to a near lesion site for treatment of an infarction in the middle cerebral artery territory. Four patients with stroke (three with ischemic and one with hemorrhagic stroke) in the middle cerebral artery territory were recruited in this study. One single dose of 2 × 10(7) UCMSCs was infused within 20 min via catheterization in the M1 segment of the middle cerebral artery. The safety and efficacy of this approach were assessed during the in-hospital and 6-month follow-up evaluation. The cell delivery was successfully performed in all of the patients, and no major accidents (stroke or death) were observed. Moreover, no fever or rash was reported. After cellular therapy, two of the three ischemic stroke patients demonstrated improved muscle strength. The improvement of the modified Rankin scale was observed in two patients, both of whom suffered from ischemic stroke at 90 and 180 days after the stem cell therapy. The hemorrhagic stroke patient failed to demonstrate improved muscle strength and did not amend his daily activities. Intra-artery delivery of UCMSCs via catheterization was a feasible and safe approach and may improve the neurological function of ischemic stroke patients with the middle cerebral artery territory infarcts.

Correlation of extracranial internal carotid artery tortuosity index and intraprocedural complications during carotid artery stenting.

BACKGROUND: To investigate the correlation between tortuosity of extracranial internal carotid artery (EICA) and intraprocedural complications in patients undergoing carotid artery stenting (CAS). METHODS: The study included 244 EICA in 223 patients undergoing CAS. Tortuosity in EICA was measured by the tortuosity index (TI). Multivariate logistic regression was performed to assess the independent risk factors of vasospasm during CAS. Receiver operating characteristic curve was performed to identify the cut-off of TI to predict vasospasm. RESULTS: During the 244 CAS, 71 EICA presented vasospasm and 114 CAS presented hypotension. High TI, long procedural duration and female are independent risk factors for vasospasm during CAS. TI of 118 was the optimal cut-off to predict vasospasm during CAS (sensitivity: 85.9%, specificity: 78.6%). Linear regression analysis demonstrated that TI is positively correlated with procedural duration (p < 0.001). There was no significant difference in TI between the hypotension and non-hypotension groups (p = 0.145). CONCLUSION: TI is an independent risk factor for vasospasm during CAS and a TI ≥118 has the high sensitivity and specificity to predict vasospasm. Our results indicate the value of assessing tortuosity of EICA prior to choosing or performing the procedure in patients with carotid stenosis or occlusion.

Stereotactic aspiration plus subsequent thrombolysis for moderate thalamic hemorrhage.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of stereotactic aspiration combined with subsequent thrombolysis in treating moderate thalamic hemorrhage (TH). METHODS: A total of 105 patients with TH were nonrandomly assigned to the conservative treatment group (n = 60) or to the aspiration group (n = 45). Patients in the aspiration group were treated with stereotactic aspiration plus subsequent thrombolysis for removal for their hematomas. RESULTS: The 30-day mortality in the conservative group was significantly higher than that in the aspiration group (28.3% (17/60) vs. 11.2% (5/45), P = 0.032). The rank of the 30-day Glasgow outcome scale in the conservative group was significantly lower than that in the aspiration group (P = 0.041), and the mean 30-day National Institutes of Health Stroke Scale score of the survivors in the conservative group was significantly higher than that in the aspiration group (16.5 ± 4. 2 vs. 14.2 ± 3.9, P = 0.012). There were a greater reduction in TH volume in the aspiration group than in the conservative group from day 1 to day 3 (-0.24% and 39.28%, respectively, P < 0.0001) and from day 1 to day 7 (26.58% and 63.26%, respectively, P < 0.0001). The rank of 90-day Glasgow outcome scale was significantly lower in the conservative group than that in the aspiration group (P = 0.015). Eighteen of 60 patients (30.0%) had a favorable outcome in the conservative group, whereas 23 of 45 patients (51.1%) had a favorable outcome in the aspiration group, and this difference was significant (P = 0.028). The 90-day cumulative mortality rate in the conservative group was significantly higher than that in the aspiration group (33.3% (20/60)) vs. 15.6% (7/45), P = 0.039). CONCLUSIONS: Stereotactic aspiration plus subsequent thrombolysis is effective and safe for moderate TH.

Montelukast inhibits matrix metalloproteinases expression in atherosclerotic rabbits.

BACKGROUND: Matrix metalloproteinases (MMPs) play important roles in the development and destabilization of atherosclerotic plaques. It is known that montelukast inhibits neointimal hyperplasia. However, the underlying mechanisms for the inhibitory effects of montelukast on neointimal formation have been poorly defined. METHODS: Thirty-six male New Zealand White rabbits were randomized as normal control, placebo (0.9% NaCl, 1.5 ml/kg/day, via intraperitoneal injection), atorvastatin (atorvastatin, 1.5 mg/kg/day, orally) and montelukast groups (montelukast, 1.5 mg/kg/day, via intraperitoneal injection). Atherosclerosis was induced by balloon-injury and high-cholesterol (HC) diet. Serum lipids were measured at 0, 8 and 12 weeks. After 12 weeks, the rabbits were sacrificed and histopathological changes examined. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to measure the expression of MMP-2 and MMP-9 in the plaques. RESULTS: It was found that montelukast reduced neointimal formation, decreased macrophage accumulation, and increased smooth muscle cells. It also attenuated the expression of MMP-2 and MMP-9 in atherosclerotic plaques, but it had no effect on plasma lipid levels. CONCLUSION: These data indicate that montelukast inhibits neointimal hyperplasia in association with decreased expression of MMP-2 and MMP-9 independent of plasma lipid levels in atherosclerotic plaques after vascular injury in hyperlipidemic rabbits.

[Effects of montelukast on atherosclerosis and monocyte chemoattractant protein-1 expression in ahypercholesterolemic rabbit model.].

OBJECTIVE: To investigate the effects of montelukast on atherosclerosis and monocyte chemoattractant protein-1 expression in a hypercholesterolemic rabbit model. METHODS: Thirty four male New Zealand white rabbits were randomized into four groups including normal control group (n = 6), placebo group (n = 8), atorvastatin group (1.5 mgxkg(-1)xd(-1), beginning at 8(th) weeks for 4 weeks, n = 10) and montelukast group (1 mgxkg(-1)xd(-1), beginning at 8(th) weeks for 4 weeks, n = 10). Rabbits except those in normal control group were fed a high cholesterol diet for 12 weeks. Serum lipids were measured at 0, 8 and 12 weeks after intervention. The intima/media ratio, percentages of macrophages or smooth muscle cells in intima and the expression of MCP-1 mRNA were examined. RESULTS: Atherosclerosis was evidenced in placebo group and atorvastatin or montelukast treatment significantly reduced neointima (0.32 +/- 0.12 and 0.34 +/- 0.10 vs. 1.12 +/- 0.36, P < 0.05) and macrophage content [(9.8 +/- 4.6)% and (11.2 +/- 3.7)% vs. (34.6 +/- 8.8)%, P < 0.05], increased SMC content [(18.6 +/- 6.9)% and (19.2 +/- 8.6)% vs. (5.2 +/- 2.3)%, P < 0.05] and inhibited expression of MCP-1 mRNA (0.42 +/- 0.08 and 0.40 +/- 0.06 vs. 2.36 +/- 0.48, P < 0.01). Montelukast had similar anti-atherogenetic effects as atorvastatin but had no influence on plasma lipids. CONCLUSIONS: Montelukast could attenuate atherosclerosis in this hypercholesterolemic rabbit model which might be attributed to its anti-inflammatory effects.

IL-18 accelerates the cell apoptosis by up-regulating cysteinyl leukotriene 2 receptor expression in human umbilical vein endothelial cells at the early stage of administration.

The purpose of the present study is to identify whether interleukin (IL)-18 can modulate cysteinyl leukotriene 2 receptor (CysLT2R) expression in Human Umbilical Vein Endothelial Cells (HUVECs) and how it influences the cell death. According to the results from real-time reverse transcription PCR, confocal laser scanning microscopy, and western blotting, a dose-dependent augmentation of CysLT2R protein expression in HUVECs was triggered by IL-18 for the first 2 h followed by down-regulation within the next 22 h after IL-18 administration. The flow cytometry showed that non-selective CysLT1R and CysLT2R antagonist BAY-u9773 could attenuate the early stage apoptosis mediated by IL-18 whereas CysLT1R antagonist Montelukast couldn't. Also, pretreatment with BAY-u9773 suppressed calcium influx of HUVECs induced by IL-18 whereas Montelukast didn't work. The observation that progression of cell death aggravated by IL-18 could be attenuated by BAY-u9773 may offer a chance to develop a novel way to treat arteriosclerosis.

Plasma C-reactive protein is related to cognitive deterioration and dementia in patients with mild cognitive impairment.

OBJECTIVE: To investigate the relationship between plasma C-reactive protein (CRP) and the risk for cognitive deterioration and development of dementia in patients with mild cognitive impairment (MCI). METHODS: Elderly Chinese patients with suspected cognitive impairment were screened. A total of 168 patients who met the criteria for MCI were enrolled. Plasma CRP levels were measured at baseline. The global cognitive functions were assessed at baseline and during follow-up periodically with Mini-Mental State Examination (MMSE). All enrolled patients were followed and evaluated regularly for 2 years to determine if the patients developed dementia. RESULTS: Of the 168 patients with MCI diagnosed at baseline, 14 (8.3%) deceased, 13 (7.7%) lost to follow-up, and 58 (34.5%) developed dementia during follow-up. MMSE score of the enrolled patients declined significantly during follow-up (22.1 +/- 3.0 vs 18.6 +/- 5.5, P < 0.001). MMSE score was significantly lower for the patients with high CRP levels than that for those with low plasma CRP levels (-4.9 +/- 5.4 vs -3.2 +/- 4.2, P < 0.05). Patients with high plasma CRP level had an increased risk for dementia and vascular dementia as compared with patients with low level of plasma CRP (Log rank test, P < 0.05). CONCLUSION: High plasma CRP level was associated with accelerated cognitive decline and increased risk for dementia in patients with MCI.