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.

Mechanical Thrombectomy for Acute Ischemic Stroke in Patients With Cardiac Myxoma: A Case Series and Pooled Analysis.

Background and Purpose: Acute ischemic stroke (AIS) is a common and life-threatening complication of patients with cardiac myxoma (CM). The role of the mechanical thrombectomy (MT) technique in CM-AIS patients remains unclear, and no guidelines exist for this population. Therefore, we conducted a case series study of MT in CM-AIS patients to investigate its safety and efficacy via a pooled analysis of published literature. Methods: Eleven CM-AIS patients who underwent MT between 2016 and 2021 were screened from multicenter stroke databases. Clinical, procedural, and outcome data were obtained from medical records. A systematic review was conducted to identify additional cases from published studies by searching PubMed and China National Knowledge Infrastructure databases. We then performed a pooled analysis of the published cases. Results: In the case series study, most patients were male (81.8%), with a median age of 51 years. All patients had CM located in the left atrium. The rate of successful reperfusion using the first-line thrombectomy technique was 100% with stent retriever (SR) and 66.7% with direct aspiration (DA), which resulted in overall successful reperfusion in 94.1% of all occlusions. The retrieved emboli of the five patients who underwent histopathology examination were identified as myxoma components. Hemorrhagic transformation was observed in five (45.5%) patients, of whom one was symptomatic (9.1%). Three-month favorable functional outcomes were achieved in five (45.5%) patients with a 3-month mortality rate of 18.2%. For the literature review, 35 cases with 51 target vessel occlusions were identified and included in the pooled analysis. The rate of successful reperfusion following first-line thrombectomy did not differ between SR (30 patients, 90.9%) and DA (10 patients, 83.3%). The overall successful reperfusion rate was 91.8% of all occlusions. Three-month favorable functional outcomes were achieved in 21 (60.0%) patients, and the mortality rate was 8.6%. Conclusions: Our findings suggest that MT is not only an effective technique but also a safe option for CM-AIS patients with large vessel occlusion. MT has several advantages for this population, which include a high recanalization rate, low bleeding risk, and the ability to evaluate the source of emboli and the etiology of stroke.

Patellar inward pushing method relieves knee osteoarthritis via regulating cytokines.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic degenerative disease characterized by pain, morning stiffness and swelling in the knee joints. And KOA is common in the elderly and seriously affects the exercise function and physical health of patients. This study aimed to explore the curative effects of patellar inward pushing method (PIPM) on KOA. MATERIAL AND METHOD: In this study, we established rabbit animal models of KOA for the research by using the New Zealand white rabbits. 30 New Zealand white rabbits were divided into 5 groups by random number table method: blank group, model group, glucosamine hydrochloride (GH) group, PIPM group and PIPM combined with GH group, then the rabbits were modeled. RESULTS: After 9-weeks cultured in groups, 5 ml blood was collected from the heart, and cytokines were detected. The result suggested that iNOS, NO and TNF-α were the pathogenic inflammatory factor of KOA, and aggravated cartilage damage and degeneration. Besides, this study indicated that PIPM combined with GH treatment significantly reduced the activity of inflammatory cytokines in serum and joint fluid of KOA models in rabbits. In addition, PIPM combined with GH therapy exhibited the best therapeutic effect among these treatments, which was working on KOA better than PIPM treatment alone or GH treatment alone. CONCLUSIONS: PIPM could effective treat KOA via regulating cytokines, and the PIPM combined with GH therapy could be a novel therapeutic strategy of KOA.

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.

Allicin Inhibits Proliferation by Decreasing IL-6 and IFN-ß in HCMV-Infected Glioma Cells.

PURPOSE: Allicin, an extract of garlic, has antitumor effects in multiple tumor types. However, the efficacy of allicin for treating glioblastoma has not yet been examined. This study examined the antitumor effect of allicin on human cytomegalovirus (HCMV)-infected glioblastoma multiforme (GBM) and its role in cytokine signaling. MATERIALS AND METHODS: HCMV-infected glioblastoma was modeled by transfection of U87MG glioblastoma cells with HMCV proteins. MTT assay was used to assess the effect of allicin on the proliferation of glioma cells. Western blot analysis was used to detect the effect of allicin on the expression of intermediate-early gene 2 (IE2) and p53. Reverse transcription-quantitative polymerase chain reaction was used to assess and the levels of interleukin (IL)-6 and interferon (IFN)-ß. Single cell gel electrophoresis was used to analyze changes in radiotherapy-induced DNA damage. RESULTS: Transfection of the IE2 protein led to decreased p53 expression and increased glioblastoma cell proliferation. Allicin inhibited this proliferation in a dose- and time-dependent manner. An inhibitory effect on cytokine release was observed in GBM cells treated with allicin. After treatment with allicin, p53 levels increased significantly, whereas expression of the inflammatory factors such as IL-6 and IFN-ß decreased. U87MG cells treated with allicin and 10 Gy irradiation had increased intracellular DNA damage compared to either treatment alone. CONCLUSION: Allicin inhibited proliferation of glioblastoma cells in vitro. Allicin also inhibited cytokine release, upregulated p53 activity, and increased the sensitivity of glioblastoma to radiotherapy. These results suggest that allicin is effective against HCMV-infected glioblastomas.

Personalizing age-specific survival prediction and risk stratification in intracranial grade II/III ependymoma.

BACKGROUND: Models for estimation of survival rates of patients with intracranial grade II/III ependymoma (EPN) are scarce. Considering the heterogeneity in prognostic factors between pediatric and adult patients, we aimed to develop age-specific nomograms for predicting 3-, 5-, and 8-year survival for these patients. METHODS: A total of 1390 cases (667 children; 723 adults) of intracranial grade II/III EPNs diagnosed between 1988 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for our study. Univariable and multivariable Cox analyses were employed to identify independent prognostic predictors. Age-specific nomograms were developed based on the results of multivariate Cox analyses. We also evaluated the performance of these predictive models by concordance index, calibration curves, time-dependent receiver operating characteristic curves, and decision curve analyses. RESULTS: Considerable heterogeneity in prognostic factors was highlighted between pediatric and adult patients. Age, sex, tumor grade, surgery treatment and radiotherapy were identified as significant predictors of overall survival for children, and age, tumor grade, tumor size, surgery treatment, and marital status for adult. Based on these factors, age-specific nomogram models were established and internally validated. These models exhibited favorable discrimination and calibration characteristics. Nomogram-based risk classification systems were also constructed to facilitate risk stratification in EPNs for optimization of clinical management. CONCLUSIONS: We developed the first nomograms and corresponding risk classification systems for predicting survival in patients with intracranial grade II/III EPN. These easily used tools can assist oncologists in making accurate survival evaluation.

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.

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.

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.

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.

The role of postoperative radiotherapy in pediatric patients with grade II intracranial ependymomas: a population-based, propensity score-matched study.

PURPOSE: The main objectives of this study were to clarify the efficacy of postoperative radiotherapy (PORT) for pediatric intracranial grade II ependymomas (EPNs) and to explore whether various characteristics are associated with different outcomes in patients with and without PORT. PATIENTS AND METHODS: Data from patients younger than 18 years diagnosed with grade II intracranial EPNs and treated by surgery, with or without PORT, were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (1973-2013 data set). Propensity score-matched analysis was conducted to balance clinical variables. Patient characteristics were stratified and analyzed. RESULTS: In total, data from 632 patients with grade II EPNs treated by cancer-directed surgery with or without PORT were obtained from the SEER database. Multivariable Cox analysis in the matched cohort suggested that undergoing PORT (overall survival [OS], P=0.020; cancer-specific survival [CSS], P=0.031), undergoing gross total resection (GTR; subtotal resection [STR] vs GTR; OS, P<0.001; CSS, P<0.001), and older age (OS, P<0.001; CSS, P<0.001) were the independent predictors of superior prognosis. Stratified analysis demonstrated that patient characteristics, including infratentorial location, younger age, and STR, were associated with benefit from PORT, while the survival advantage was not detected in patients who underwent GTR. CONCLUSION: Propensity score-matched analysis using SEER data indicates survival advantages of PORT. Given the strong prognostic associations with extent of resection and patient age, we recommend PORT for younger patients treated by STR.

The effects of tumor size and postoperative radiotherapy for patients with adult low-grade (WHO grade II) infiltrative supratentorial astrocytoma/oligodendroglioma: A population-based and propensity score matched study.

BACKGROUND: The update of 2018 NCCN guidelines (central nervous system cancers) recommended the risk classification of postoperative patients diagnosed as adult low-grade (WHO grade II) infiltrative supratentorial astrocytoma/oligodendroglioma (ALISA/O) should take tumor size into consideration. Moreover, the guidelines removed postoperative radiotherapy (PORT) for low risk patients. Our study aimed to explore the specific tumor size to divide postoperative patients into relatively low- or high risk subgroups and the effect of PORT for ALISA/O patients. METHODS: We conducted a retrospective study choosing 1277 postoperative ALISA/O patients from the Surveillance, Epidemiology, and End Results database. The X-tile analysis provided the optimal cutoff point based on tumor size. The differences between surgery alone and surgery +RT groups were balanced by propensity score-matched analysis. The multivariable analysis and the nomogram evaluated multiple prognostic factors based on cancer-specific survival (CSS) and overall survival (OS). RESULTS: X-tile plots defined 59 mm (P < 0.001) as the optimal cutoff tumor size value in terms of CSS, which was verified in multivariate analysis (P < 0.001). The Kaplan-Meier analysis showed that the surgery alone had higher CSS and OS than surgery +RT, while the low risk group had no statistical significance after propensity score match. Multivariable analysis showed that surgery +RT was independently associated with diminished OS and CSS for high risk group, which had no statistical significance for low-risk group. CONCLUSIONS: Our study suggested that tumor size of 59 mm was an optimal cutoff point to divide postoperative patients into relatively low- or high risk subgroups. PORT may not benefit patients, while the effects of PORT for low risk patients need further research.

Na+/K+­ATPase DR region­specific antibody protects U251 cells against hypoxia reperfusion­induced injury via the PI3K/AKT and ERK pathways.

Cerebral ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and to the death of brain tissue or cerebral infarction/ischemic stroke. In the present study, an Na+/K+­ATPase (NKA) DR region­specific antibody (DRSAb) was established and purified and it was demonstrated that DRSAb induced a protective effect on human astrocytes (U251) via the phosphoinositide 3­kinase (PI3K)/AKT and extracellular signal­regulated protein kinase (ERK) signaling pathways. The binding of DRSAb on NKA was revealed using flow cytometry. High signals were detected on U251 cells incubated with DRSAb, but not with control sera or BSA. The viability of the hypoxia/reperfusion (H/R)­treated cells was markedly increased by DRSAb administration of 0.3­0.5 µM. The optimal concentration of DRSAb was 0.4 µM for attenuation of the injury induced by H/R. The administration of 0.4 µM DRSAb markedly reduced the number of apoptotic cells compared with control sera. The application of PD98059, an ERK inhibitor, and LY­294002, an AKT inhibitor, attenuated the protective effect induced by DRSAb in the U251 cells subjected to H/R. Furthermore, the application of LY294002 prior to incubation with DRSAb eliminated the activation of ERK1/2, whereas the use of PD98059 failed to attenuate the effect of DRSAb on PI3K/AKT activation. These results indicated that the protective effects of DRSAb against H/R injury in U251 cells occurred via stimulation of the PI3K/AKT and ERK signaling pathways.

Traumatic open depressed cranial fracture causing occlusion of posterior superior sagittal sinus: Case report.

RATIONALE: The superior sagittal sinus (SSS) is the major dural sinuses that receive a considerable amount of venous drainage. Interruption of its posterior third has been suggested to cause intracranial hypertension and lead to potentially fatal consequences. PATIENT CONCERNS: We presented a 22-year-old man with a severe headache and scalp bleeding after a head chop wound. Physical examination identified a 20-cm straight laceration in his parietooccipital scalp. Computed tomography (CT) demonstrated a depressed cranial fracture (DCF) in the left parietooccipital bone, a fracture line across the midline to the right side, and penetrations of bone fragments into the brain parenchyma. DIAGNOSES: Traumatic open DCF in left parietooccipital bone. INTERVENTIONS: An emergent left parietooccipital craniotomy, followed by cranioplasty to restore the depressed bone flap, was delivered to the patient. Postoperative CT confirmed successful elevation of the DCF and removal of intracerebral bone fragments. However, postoperative CT angiography (CTA) demonstrated an absence of venous flow distal to the fracture, suggesting occlusion of the posterior third of SSS. MRV revealed a persistent absence of venous flow in the posterior third of SSS with dilated cortical venous drainage. Anticoagulation treatment was initiated 3 days after surgery, and follow-up CTA and digital subtraction angiography showed gradually improved patency in the anterior and middle two-thirds of SSS. OUTCOMES: Despite occlusion of the posterior third of SSS, patient's symptoms resolved after the operation and he was discharged without complications. LESSONS: The favorable clinical outcome after complete occlusion of the posterior third of the SSS has rarely been reported and it might be explained by our timely surgical intervention and development of compensatory cerebral collateral circulation.

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.

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.

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.