Rapid Clot Reduction with Direct Aspiration via 8-F Guide Catheter for Cardioembolic Extracranial Carotid Artery Occlusion: A Guide Catheter Aspiration Technique.

This study reported data that were collected from 11 consecutive patients undergoing treatment for acute cardioembolic extracranial carotid artery (ECCA) occlusion with extensive clot burden via the guide catheter aspiration (GCA) technique. The GCA technique was performed as a direct aspiration using 2 60-mL syringes simultaneously through an 8-F guide catheter. Successful reperfusion was achieved in all 11 patients at the end of thrombectomy, and successful reperfusion was observed in 4 patients after a single GCA procedure pass. A favorable clinical outcome was achieved in 6 (54.5%) cases after 90 days. Thus, the GCA technique is efficacious for patients with cardioembolic ECCA occlusions.

Etanercept alleviates early brain injury following experimental subarachnoid hemorrhage and the possible role of tumor necrosis factor-α and c-Jun N-terminal kinase pathway.

Cerebral inflammation plays a crucial role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). This study investigated the effects of c-Jun N-terminal kinase (JNK) inhibitor SP600125, acetylcholine (Ach), etanercept, and anti-TNF-α on cellular apoptosis in the cerebral cortex and the hippocampus, in order to establish the role of JNK and TNF-α in EBI. The SAH model was established using an endovascular puncture protocol. The reliability of the EBI model was determined by phosphorylated-Bad (pBad) immunohistochemistry. Neurological scores were recorded and western blot was used to detect the expression of JNK and TNF-α, and TUNEL assay was used to mark apoptotic cells. The results showed that pBad positive cells were evenly distributed in the cerebral cortex at different time points. The highest expression of pBad was reached 1 day after SAH, and pJNK and TNF-α reached their peak expression at 2 days after SAH. SP600125, Ach, and etanercept significantly decreased the level of pJNK and TNF-α in the cerebral cortex and the hippocampus. In addition, SP600125 and etanercept reduced cellular apoptosis in the cerebral cortex and the hippocampus and significantly improved neurological scores at 2 days after SAH potentially via inhibition of the JNK-TNF-α pathway. Ach reduced cellular apoptosis only in the cerebral cortex. It is possible that JNK induces TNF-α expression, which in turn enhances JNK expression in EBI after SAH, leading to increased apoptosis in the cerebral cortex and the hippocampus. Thus, our results indicate that that etanercept may be a potential therapeutic agent to alleviate EBI.

The rapid lipopolysaccharide-induced release of matrix metalloproteinases 9 is suppressed by simvastatin.

A rapid increase in matrix metalloproteinase-9 (MMP-9) expression by stimulated leukocytes is common in many diseases. Recent evidence suggests that the beneficial effects of statins are mediated in part by the suppression of MMP-9 release. In this study, we investigated the effect of statin on MMP-9 expression and its antagonist, tissue inhibitor of metalloproteinase-1 (TIMP-1) in LPS-stimulated leukocytes. Rat neutrophils and monocytes were stimulated with lipopolysaccharide (LPS) in the presence of simvastatin. MMP-9 secretion and mRNA expression were analyzed using ELISA and RT-PCR, respectively. Total MMP-9 protein production was measured by Western blot analysis. Potential signal transduction pathways responsible for MMP-9 production were investigated using luciferase reporter assays (NF-κB), pull-down assays (RhoA), and pharmacological inhibition. Our data show that MMP-9 and TIMP-1 expression are differentially induced by LPS in neutrophils and monocytes. We showed that rapid MMP-9 release occurred mainly via secretion from intracellular stores. Moreover, we showed that statin significantly suppressed LPS-induced MMP-9 release and mRNA expression in a time- and concentration-dependent manner. We also evaluated that simvastain postponed the rapid LPS-induced MMP-9 release for about 20 min. In conclusion, we demonstrated that the suppressive effect of simvastatin on LPS-stimulated MMP-9 release does not occur via the NF-κB pathway and the MAPKs pathway, but via the RhoA/ROCK pathway.

Role of the AMPK signaling pathway in early brain injury after subarachnoid hemorrhage in rats.

BACKGROUND: AMP-activated protein kinase (AMPK) is a key metabolic and stress sensor/effector. Few investigations have been performed to study the role of AMPK in subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was undertaken to investigate the time course of AMPK activation in the early stage of SAH and to evaluate the influence of AICAR (which is known to mimic AMP and activates AMPK) and compound C (a commonly used AMPK inhibitor) on EBI in rats following SAH. METHODS: Adult male rats were divided into six groups: control, sham, SAH, SAH + vehicle, SAH + AICAR and SAH + compound C. SAHs were induced by a modified endovascular perforation method. Immunohistochemistry, real-time PCR and Western blot were used to detect the spatial and dynamic expression of AMPK after SAH. Cortical apoptosis and the expressions of apoptosis-related proteins such as FOXO3a (forkhead box, class O, 3a) and Bim (Bcl-2-interacting mediator of cell death) were detected after different drug interventions. RESULTS: We found SAH induced prolonged activation of AMPK. Treatment with AICAR markedly induced overactivation of AMPK and upregulation of FOXO3a and Bim. AICAR also significantly exacerbated cerebral apoptosis and neurological impairment following SAH. On the other hand, pre-administration of compound C attenuated EBI in this SAH model by modulating cerebral apoptosis by inhibiting FOXO3a and Bim. CONCLUSIONS: Our findings suggest that the AMPK pathway may play an important role in SAH-induced neuronal apoptosis, and the use of AMPK inhibitors can provide neuroprotection in EBI after SAH.

Dynamic expression of the suppressor of cytokine signaling-3 and cytokines in the cerebral basilar artery of rats with subarachnoid hemorrhage, and the effect of acetylcholine.

BACKGROUND: There are complex interactions between acetylcholine (ACh), the suppressor of cytokine signaling-3 (SOCS-3), and cytokines, however, little is known about their dynamic expression or their effects on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Therefore, we aimed to describe and clarify the dynamic expression of SOCS-3 and cytokines after SAH, as well as the relationships between the levels of SOCS-3, cytokines, and ACh. METHODS: The rat model of single cisterna magna injection was used to mimic acute SAH. The degree of CVS was indicated by lumen diameter and artery wall thickness under H&E staining. A semi-quantitative immunohistochemical analysis method was used to clarify the role of SOCS-3 in the CVS after SAH. We also measured the content of IL-6 and IL-10 in cerebrospinal fluid. RESULTS: We found that SOCS-3 expression levels increased rapidly within 12 h after SAH, more slowly after 12 h, and did not reach a peak within 48 h. Interleukin 6 (IL-6) levels rapidly increased within 24 h after SAH, reached a peak 24 h after SAH, and decreased slightly at 48 h. IL-10 levels increased during the first 6 h after SAH, after which this increase tapered off. ACh treatment reduced IL-6 levels and resulted in elevated levels of SOCS-3, but had no effect on IL-10 expression. Furthermore, ACh treatment relieved basilar arterial vasospasm, whereas mecamylamine pretreatment counteracted the activity of ACh. CONCLUSIONS: Taken together, these data indicate that SOCS-3 was involved in vasospasm via an IL-6- and IL-10-related mechanism, and that CVS following SAH could be reversed by the intraventricular injection of ACh.

The role of rosiglitazone in the proliferation of vascular smooth muscle cells after experimental subarachnoid hemorrhage.

BACKGROUND: Recent evidence has demonstrated that rosiglitazone can attenuate cerebral vasospasm following subarachnoid hemorrhage (SAH). Some studies have shown that rosiglitazone can suppress inflammation and immune responses after SAH. However, the precise molecular mechanisms by which cerebral vasospasm is attenuated is not clear. METHODS: In this study, SAH was created using a "double hemorrhage" injection rat model. Rats were randomly divided into three groups and treated with saline (control group), untreated (SAH group), or treated with rosiglitazone. Using immunocytochemistry, hematoxylin and eosin (HE) staining, and measurement of the basilar artery, we investigated the formation of pathologic changes in the basilar artery, measured the expression of caveolin-1 and proliferating cell nuclear antigen (PCNA), and investigated the role of rosiglitazone in vascular smooth muscle cell (VSMC) proliferation in the basilar artery after SAH. RESULTS: In this study, we observed significant pathologic changes in the basilar artery after experimental SAH. The level of vasospasm gradually increased with time during the 1st week, peaked on day 7, and almost recovered on day 14. After rosiglitazone treatment, the level of vasospasm was significantly attenuated in comparison with the SAH group. Immunocytochemistry staining showed that caveolin-1 expression was significantly increased in the rosiglitazone group, compared with the SAH group. Inversely, the expression of PCNA showed a notable decrease after rosiglitazone treatment. CONCLUSIONS: The results indicate that rosiglitazone can attenuate cerebral vasospasm following SAH. Up-regulation of caveolin-1 by rosiglitazone may be a new molecular mechanism for this response, which is to inhibit proliferation of VSMCs after SAH, and this study may provide a novel insight to prevent delayed cerebral vasospasm (DCVS).

Abnormal developmental of structural covariance networks in young adults with heavy cannabis use: a 3-year follow-up study.

Heavy cannabis use (HCU) exerts adverse effects on the brain. Structural covariance networks (SCNs) that illustrate coordinated regional maturation patterns are extensively employed to examine abnormalities in brain structure. Nevertheless, the unexplored aspect remains the developmental alterations of SCNs in young adults with HCU for three years, from the baseline (BL) to the 3-year follow-up (FU). These changes demonstrate dynamic development and hold potential as biomarkers. A total of 20 young adults with HCU and 22 matched controls were recruited. All participants underwent magnetic resonance imaging (MRI) scans at both the BL and FU and were evaluated using clinical measures. Both groups used cortical thickness (CT) and cortical surface area (CSA) to construct structural covariance matrices. Subsequently, global and nodal network measures of SCNs were computed based on these matrices. Regarding global network measures, the BL assessment revealed significant deviations in small-worldness and local efficiency of CT and CSA in young adults with HCU compared to controls. However, no significant differences between the two groups were observed at the FU evaluation. Young adults with HCU displayed changes in nodal network measures across various brain regions during the transition from BL to FU. These alterations included abnormal nodal degree, nodal efficiency, and nodal betweenness in widespread areas such as the entorhinal cortex, superior frontal gyrus, and parahippocampal cortex. These findings suggest that the topography of CT and CSA plays a role in the typical structural covariance topology of the brain. Furthermore, these results indicate the effect of HCU on the developmental changes of SCNs in young adults.

Age and duration of hypertension are associated with carotid artery tortuosity.

Objective: Tortuosity of the carotid artery is a common angiographic finding that may impact blood flow and neuronal function. However, information on its prevalence and risk factors remains limited. In this study, we determined to explore the factors affecting carotid artery tortuosity. Methods: The head and neck computed tomography angiography (CTA) imaging and cerebral angiography data performed at the Second Affiliated Hospital of Wenzhou Medical University between January 2019 and September 2021 were collected, and a total of 356 cases were enrolled in the study after screening. Carotid artery tortuosity refers to the angle between the two adjacent segments of the carotid artery, from the opening of the aortic arch on either side to the external orifice of the carotid canal, being less than 150°. A retrospective analysis was performed to compare the general information, laboratory indicators, personal history, and medical history between the two groups. The χ2 test, t-test, and Mann-Whitney U-test were performed to compare the parameters between the two groups. If there were significant differences between the groups, multivariate logistic regression was performed to analyze the factors affecting carotid artery tortuosity. Results: A total of 222 of the 356 cases were determined to have carotid artery tortuosity, accounting for 63.6%. There were statistically significant differences in age, body mass index (BMI), duration of diabetes and hypertension, levels of low-density lipoprotein cholesterol (LDL-C), diastolic blood pressure, history of ischemic and hemorrhagic stroke, and the usage of antihypertensive drugs between the two groups. Multivariate logistic regression analysis of the above factors showed that age (OR = 5.063, 95% CI 2.963-10.26, p < 0.001) and duration of hypertension (OR = 2.356, 95% CI 1.353-8.625, p = 0.021) were associated with a higher incidence of carotid artery tortuosity. Compared to patients who did not consume antihypertensive drugs, the incidence of carotid artery tortuosity was significantly less (OR = 0.094, 95% CI 0.002-0.713, p = 0.019) in those consuming antihypertensive drugs. Conclusion: Carotid artery tortuosity is a relatively common carotid artery disease. The incidence of carotid artery tortuosity may increase with age and the duration of hypertension. The consumption of antihypertensive drugs may reduce the incidence of carotid artery tortuosity.

Aspiration catheter tip flutter is a reliable indicator of successful clot aspiration in ADAPT.

BACKGROUND: A direct aspiration first pass technique (ADAPT) has emerged as a fast, safe, and efficacious method for treating acute large vessel occlusion. However, successful clot aspiration is not guaranteed in every ADAPT procedure. We have observed that when the catheter effectively ingested the clot, the catheter tip displayed a distinct fluttering motion, referred to herein as tip flutter. Thus this study aimed to assess whether this catheter tip flutter can be used as a sign of successful clot aspiration. METHODS: This retrospective study included 231 consecutive patients admitted to our institution due to acute ischemic stroke and treated with ADAPT between October 2018 and November 2023. We obtained baseline and procedural data from all patients. Additionally, we assessed the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the tip flutter in predicting clot aspiration. RESULTS: The incidence of embolus translocation was significantly higher in the tip flutter positive group than in the tip flutter negative group (P<0.001). Also, hyperdense artery presentation was more prevalent in the positive group (P<0.001), whereas the clot burden score was higher in the negative group (P=0.002). Clot aspiration in the first pass occurred in 83 (96.5%) and 37 (25.5%) patients in the positive and negative groups, respectively (P<0.001). Multivariable logistic regression analysis showed the tip flutter sign (OR 1.09, 95% CI 0.16 to 1.29; P<0.001) was an independent predictor of successful clot aspiration. Sensitivity, specificity, PPV, NPV, and accuracy of the tip flutter for predicting clot aspiration were 69.2%, 97.3%, 96.5 %, 74.5%, and 82.7%, respectively. CONCLUSIONS: In this study, we found that tip flutter was a reliable indicator of successful clot aspiration during ADAPT.

Role of Akt signaling pathway in delayed cerebral vasospasm after subarachnoid hemorrhage in rats.

BACKGROUND: Akt plays an important role in cell survival, proliferation, apoptosis and other activities. It also has been involved in maintaining smooth muscle cell contraction phenotypes in vitro and in vivo. Recent studies have focused on the inhibition of Akt in acute vasospasm and neuronal apoptosis after subarachnoid hemorrhage (SAH). However, its role in delayed cerebral vasospasm (DCVS) has not been reported. METHODS: In this study, using a "two-hemorrhage" rat model of SAH, we examined the expression of p-Akt and the formation of vasospasm in the basilar arteries. To investigate the possible role of Akt in phenotypic switching, we performed immunohistochemical staining to examine expressions of SMα-actin and proliferating cell nuclear antigen (PCNA), markers of smooth muscle phenotypic switching. RESULTS: We found that the basilar arteries exhibited vasospasm after SAH and that vasospasm became most severe on day 7 after SAH. Elevated protein expression of p-Akt was detected 4 days after SAH induction, peaked on day 7, and recovered on day 21, which was in a parallel time course to the development of DCVS. Moreover, results of immunohistochemical staining revealed enhanced expression of PCNA but gradual reduction in expression of SMα-actin from day 1 to day 7 after SAH; then, the expressions of PCNA and SMα-actin gradually recovered until day 21. CONCLUSIONS: These results support a novel mechanism in which the Akt signaling pathway plays an important role in the proliferation of smooth muscle cells (SMCs) rather than inducing phenotype switching in basilar arteries, which promotes the development of DCVS after SAH.

De novo brain arteriovenous malformation formation and development: A case report.

BACKGROUND: Brain arteriovenous malformation (AVM), an aberrant vascular development during the intrauterine period, is traditionally considered a congenital disease. Sporadic reports of cases of de novo AVM formation in children and adults have challenged the traditional view of its congenital origin. CASE SUMMARY: In this report, we have presented the case of a child with a de novo brain AVM. Magnetic resonance imaging and magnetic resonance angiography of the brain showed no AVM at the age of 5 years and 2 mo. Brain AVM was first detected in this child at the age of 7 years and 4 mo. The brain AVM was significantly advanced, and hemorrhage was seen for the first time at the age of 12 years and 8 mo. There was further progression in the AVM, and hemorrhage occurred again at the age of 13 years and 5 mo. Genetic analysis of this patient revealed a mutation in the NOTCH2 (p.Asp473Val) gene. CONCLUSION: In short, our case has once again confirmed the view that brain AVM is an acquired disease and is the result of the interaction of genes, environment, and molecules.

Successful treatment of pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii with multi-route tigecycline: A case report.

BACKGROUND: Pyogenic ventriculitis caused by extensively drug-resistant Acinetobacter baumannii (A. baumannii) is one of the most severe complications associated with craniotomy. However, limited therapeutic options exist for the treatment of A. baumannii ventriculitis due to the poor penetration rate of most antibiotics through the blood-brain barrier. CASE SUMMARY: A 68-year-old male patient with severe traumatic brain injury developed pyogenic ventriculitis on postoperative day 24 caused by extensively drug-resistant A. baumannii susceptible to tigecycline only. Successful treatment was accomplished through multi-route administration of tigecycline, including intravenous combined with continuous ventricular irrigation plus intraventricular administration. The pus was cleared on the 3rd day post-irrigation, and cerebrospinal fluid cultures were negative after 12 d. CONCLUSION: Our findings suggest that multi-route administration of tigecycline can be a therapeutic option against pyogenic ventriculitis caused by extensively drug-resistant A. baumannii.

Case Report: Whole-Exome Sequencing of Hypothalamic Hamartoma From an Infant With Pallister-Hall Syndrome Revealed Novel de novo Mutation in the GLI3.

Background: GLI-Kruppel family member 3 (GLI3), a zinc finger transcription factor of the sonic hedgehog pathway, is essential for organ development. Mutations in GLI3 cause several congenital conditions, including Pallister-Hall syndrome (PHS), which is characterized by polydactyly and hypothalamic hamartoma. Most patients are diagnosed soon after birth, and surgical removal of hypothalamic hamartoma in the very young is rarely performed because of associated risks. Case presentation: A 7-month-old boy with PHS features, including a suprasellar lesion, bifid epiglottis, tracheal diverticulum, laryngomalacia, left-handed polydactyly and syndactyly, and omental hernia was referred to our service. His suprasellar lesion was partially removed, and whole-exome sequencing was applied to the resected tumor, his peripheral blood, and blood from his parents. Histopathology confirmed the diagnosis of hypothalamic hamartoma, and molecular profiling revealed a likely pathogenic de novo variant, c.2331C>G (p. H777Q), in GLI3. Magnetic resonance imaging follow-up 1 year later showed some residual tumor, and the patient experienced normal development post operation. Conclusions: We presented a case of PHS that carries a novel GLI3 variant. Hypothalamic hamartoma showed a distinct genetic landscape from germline DNA. These data offer insights into the underlying etiology of hypothalamic hamartoma development in patients with PHS.

Titanium mesh cranioplasty in pediatric patients after decompressive craniectomy: Appropriate timing for pre-schoolers and early school age children.

PURPOSE: There is little knowledge on the growth of cranial defects, appropriate timing and outcomes of application of titanium mesh for cranioplasty in the pediatric population, especially pre-school age (2-5 years old) and school age (6-12 years old) children. We hypothesised that cranioplasty for pre-schoolers could be delayed to school age due to the expected cranium growth, whereas, for the school age group, it is better to perform routine cranioplasty (3-6 months) to protect the brain and therefore ensure their timely return to school life. MATERIALS AND METHODS: A retrospective review of pediatric patients (2-12 years old) who underwent titanium mesh cranioplasty for cranial defects from 2006 to 2012 was performed. Patient demographic data, radiological data, and clinical information were collected. Specifically, cranial defect sizes were evaluated by three-dimensional (3D) reconstruction of computed tomography data after craniectomy, before cranioplasty and 2-years after cranioplasty. Patients were routinely followed up at an outpatient clinic for complications and school attendance. RESULTS: A total of 18 titanium mesh cranioplasties were performed in 18 patients. The average interval between craniectomy and cranioplasty was 3 years for pre-schoolers and 4 months for the school age group. Patients in the pre-schooler group showed significant enlargements in cranial defects during the interval as compared with the school age group (26% vs. 4%, P < 0.05). There were no surgery-related complications except in one patient, who had titanium mesh exposure 11 months later. Two years after cranioplasty, there was no significant difference in mild cranial defect enlargements between the two groups (11% vs. 6%, P > 0.05). Patients were followed for an average of 5 (range, 2-8) years. All patients had satisfactory recovery of cranial contour, sufficient protection of the brain and active participation in school study. All patients had satisfactory recovery of cranial contour, sufficient protection of the brain and active participation in school. CONCLUSION: Timing of titanium mesh cranioplasty after decompressive craniectomy based on their age is a workable solution for school-age pediatric patients. The enlargement of cranium defects in pre-schoolers supports a delayed repair until school age. The long-term outcomes for these patients with titanium mesh cranioplasty are favourable.

Longitudinal Changes in Diffusion Tensor Imaging Following Mild Traumatic Brain Injury and Correlation With Outcome.

The chronic consequences of traumatic brain injury (TBI) may contribute to the increased risk for early cognitive decline and dementia, primarily due to diffusion axonal injury. Previous studies in mild TBI (mTBI) have been controversial in describing the white matter tract integrity changes occurring at acute and subacute post-injury. In this prospective longitudinal study, we aim to investigate the longitudinal changes of white matter (WM) using diffusion tensor imaging (DTI) and their correlations with neuropsychological tests. Thirty-three patients with subacute mTBI and 31 matched healthy controls were studied with an extensive imaging and clinical battery. Neuroimaging was obtained within 7 days post-injury for acute scans and repeated at 1 and 3 months post-injury. Using a region-of-interest-based approach, tract-based spatial statistics was used to conduct voxel-wise analysis on diffusion changes in mTBI and was compared to those of healthy matched controls, scanned during the same time period and rescanned with an interval similar to that of patients. We found decreased fractional anisotropy (FA) values in the left anterior limb of internal capsule (ALIC) and right inferior fronto-occipital fasciculus (IFOF) during the 7 days post-injury, which showed longitudinal evidence of recovery following 1 month post-injury. Increased FA values in these two tracts at 1 month post-injury were positively associated with better performance on cognitive information processing speed at initial assessment. By contrast, there were also some tracts (right anterior corona radiata, forceps major, and body of corpus callosum) exhibiting the continuing loss of integrity sustaining even beyond 3 months, which can predict the persisting post-concussion syndromes. Continuing loss of structural integrity in some tracts may contribute to the persistent post-concussion syndromes in mTBI patients, suggesting certain tracts providing an objective biomarker for tracking the pathological recovery process following mTBI.

Epidemiological trends, relative survival, and prognosis risk factors of WHO Grade III gliomas: A population-based study.

BACKGROUND: Population-based studies on grade III gliomas are still lacking. The purpose of our study was to investigate epidemiological characteristics, survival, and risk factors of these tumors. PATIENTS AND METHODS: All data of patients with grade III gliomas were extracted from the Surveillance, Epidemiology, and End Results database. This database provides analysis to evaluate age-adjusted incidence, incidence-based mortality, and limited-duration prevalence. The trends of incidence and mortality were modeled using Joinpoint program. Relative survival was also available in this database. Univariate and multivariate analyses were used to access the prognostic significance of risk factors on cancer-specific survival. Nomogram was constructed to predict 3-, 5-, and 10-year survival. RESULTS: Our study showed that during 2000-2013, the incidence was stable and the mortality rate dropped significantly with APC as -1.95% (95% CI: -3.35% to -0.54%). Patients aged 40-59 had the highest prevalent cases. The 1-, 3-, 5-, and 10-year relative survival rates for all patients were 74.7%, 52.8%, 44.4%, and 32.4%. And it varied by risk factors. Cox regression analysis showed older age, male, black race, divorced status, histology of AA, tumor size <3.5 cm and no surgery were associated with worse survival. CONCLUSION: Our study provides reasonable estimates of the incidence, mortality, and prevalence for patients with grade III gliomas during 2000-2013. The results of relative survival and Cox regression analysis revealed that age, race, sex, year of diagnosis, tumor site, histologic type, tumor size, and surgery were the identifiable prognostic indicators. The effects of radiotherapy still need further study. We integrated these risk factors to construct an effective clinical prediction model.

Simvastatin pretreatment ameliorates t-PA-induced hemorrhage transformation and MMP-9/TIMP-1 imbalance in thromboembolic cerebral ischemic rats.

Background: The use of thrombolysis with tissue-plasminogen activator (t-PA) in patients with acute ischemic stroke (AIS) is limited by increased levels of matrix metalloproteinase-9 (MMP-9) and by the increased risk of hemorrhagic transformation (HT). In this study, we investigated the effects of simvastatin pretreatment on t-PA-induced MMP-9/tissue inhibitor of metalloproteinase-1 (TIMP-1) imbalance and HT aggravation in a rat AIS model. Methods: The rat AIS model was established by autologous blood emboli. Two weeks before surgery, rats were pretreated with simvastatin (60 mg/kg/d), and three hours after surgery, t-PA (10 mg/kg) was administered. MMP-9 and TIMP-1 levels in the infarcted zone and plasma were evaluated by Western blot analysis and ELISA; the level of HT was quantified by determining the hemoglobin content. RhoA activation was determined to clarify the potential effect. Results: The results suggested that pretreatment with simvastatin suppressed the increase in t-PA-induced MMP-9 levels and neutralized the elevated MMP-9/TIMP-1 ratio, but had no effect on TIMP-1 levels. Thrombolysis with t-PA after ischemia improved neurological outcome, but increased intracranial hemorrhage. Moreover, t-PA-induced HT aggravation was reduced by simvastatin pretreatment. In addition, we showed that t-PA-induced activation of RhoA was suppressed by simvastatin, and that t-PA-induced MMP-9/TIMP-1 imbalance and hemorrhage was reduced by Rho kinases (ROCK) inhibitor Y-27632. Conclusion: In this study, we showed that simvastatin pretreatment ameliorated t-PA-induced HT and MMP-9/TIMP-1 imbalance, and demonstrated that the RhoA/ROCK pathway was implicated.

Trends in intracranial meningioma incidence in the United States, 2004-2015.

BACKGROUND: Meningioma incidence was reported to have risen substantially in the United States during the first decade of the 21st century. There are few reports about subsequent incidence trends. This study provides updated data to investigate trends in meningioma incidence by demographic and tumor characteristics at diagnosis in the United states from 2004 to 2015. METHODS: Trends in meningioma incidence were analyzed using data from the Surveillance, Epidemiology, and End Results-18 (SEER-18) registry database of the National Cancer Institute. The joinpoint program was used to calculate annual percent change (APC) in incidence rates. RESULTS: The overall incidence of meningioma increased by 4.6% (95% CI, 3.4-5.9) annually in 2004-2009, but remained stable from 2009 to 2015 (APC, 0; 95% CI, -0.8 to 0.8). Females (10.66 per 100 000 person-years) and blacks (9.52 per 100 000 person-years) had significant predominance in meningioma incidence. Incidence in many subgroups increased significantly up to 2009 and then remained stable until 2015. However, meningioma incidence in young and middle-aged people increased significantly throughout the entire time period from 2004 to 2015 (APC: 3.6% for <20-year-olds; 2.5% for 20-39-year-olds; 1.8% for 40-59-year-olds). The incidence of WHO II meningioma increased during 2011-2015 (APC = 5.4%), while the incidence of WHO III meningioma decreased during 2004-2015 (APC = -5.6%). CONCLUSION: In this study, the incidence of meningioma was found to be stable in recent years. Possible reasons for this finding include changes in population characteristics, the widespread use of diagnostic techniques, and changes in tumor classification and risk factors in the US population.

Solitaire Stent Permanent Implantation as an Effective Rescue Treatment for Emergency Large Artery Occlusion.

BACKGROUND: In this study, we present our experiences on the feasibility of rescue permanent Solitaire stent placement for failed mechanical thrombectomy (MT) and our protocol to avoid ineffective stent placement. METHODS: We retrospectively evaluated the data for consecutive patients admitted into the Second Affiliated Hospital of Wenzhou Medical University and 2 collaboration hospitals from August 2014 to May 2018 for emergency large artery occlusion. The baseline clinical characteristics and radiologic assessment, interventional data, clinical outcome, and angiographic follow-up data were assessed. Notably, we introduced our protocol for antegrade flow assessment before Solitaire stent detachment to ensure an effective stent implantation. RESULTS: Thirty-nine patients (mean age, 68.1 years, mean preprocedural National Institute of Health Scale Score, 22.1) were included, in which 34 patients had anterior circulation large artery occlusion and 5 patients had posterior circulation large artery occlusion. The MT attempts ranged from 1-5 (3.6 on average). The mean onset-to-puncture time was 4.8 hours (ranging from 2.1-7.8 hours) and the mean procedure time was 87.4 minutes (ranging from 32-124 minutes). Modified thrombolysis in cerebral infarction 2b-3 reperfusions were noted in all cases. The immediate, average postprocedure stenosis rate was 25.3%, and the average stenosis rate at the 3-month angiographic follow-up was 34.7% (data from 15 patients). Three patients died. Nineteen (48.7%) patients had good outcome (modified Rankin Scale, mRS ≤2) at the 3-month follow-up. CONCLUSIONS: Permanent Solitaire stent placement might be a feasible therapy for patients with MT-failed emergency large artery occlusion. For a successful revascularization, careful antegrade flow assessment before stent detachment is critical.

AG490 ameliorates early brain injury via inhibition of JAK2/STAT3-mediated regulation of HMGB1 in subarachnoid hemorrhage.

High mobility group box 1 (HMGB1) is a classic damage-associated molecular pattern that has an important role in the pathological inflammatory response. In vitro studies have demonstrated that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is involved in the regulation of HMGB1 expression, mediating the inflammatory response. Therefore, the purpose of the present study was to evaluate JAK2/STAT3 pathway involvement in the subarachnoid hemorrhage (SAH)-dependent regulation of HMGB1, using an in vivo rat model. A SAH model was established by endovascular perforation. Western blotting, immunohistochemistry and immunofluorescence were used to analyze HMGB1 expression after SAH. In addition, the effects of AG490 after SAH on JAK2/STAT3 phosphorylation, HMGB1 expression and brain damage were evaluated. The results of the present study demonstrated that JAK2/STAT3 was significantly phosphorylated (P<0.05) and the total HMGB1 protein level was significantly increased (P<0.05) after SAH. In addition, the cytosolic HMGB1 level after SAH demonstrated an initial increase followed by a decrease to the control level, while the nuclear HMGB1 level after SAH demonstrated the opposite trend, with an initial decrease and subsequent increase. AG490 administration after SAH significantly inhibited JAK2/STAT3 phosphorylation (P<0.05), suppressed the expression and translocation of HMGB1, reduced cortical apoptosis, brain edema and neurological deficits. These results demonstrated the involvement of the JAK2/STAT3 pathway in HMGB1 regulation after SAH.