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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Optic nerve injury-associated blunt cerebrovascular injury: Three case reports.

RATIONALE: Blunt cerebrovascular injury (BCVI) is a rare complication that may occur after craniocervical trauma. The current literature is limited to extracranial carotid artery injuries; however, no reports have been published on blunt intracranial carotid injury (BICI), especially those associated with optic nerve injury. PATIENT CONCERNS: Here we report on 3 BICI cases that demonstrated optic nerve injuries after craniofacial injuries. All 3 patients showed post-trauma vision loss on the injured side. DIAGNOSES: Optical canal fractures can be found in these patients, and carotid sulcus was compressed by the fragments. Computed tomography angiography (CTA) and digital subtraction angiography (DSA) were performed in all 3 patients. INTERVENTIONS: Case 1 was given no further treatment, except for symptomatic support and rehabilitation therapy. Case 2 was treated with antiplatelet therapy for 3 days, and then a stent was inserted in the injured internal carotid. Case 3 received antiplatelet therapy and a internal carotid compression test was performed simultaneously for 2 weeks, then the injured internal carotid was completely blocked. OUTCOMES: Case 1 developed cerebral infarction that resulted in unilateral hemiplegia. Due to timely treatment, the remaining 2 patients had a better prognosis. LESSONS: CTA should be performed primarily to exclude vascular injury and for CTA-positive patients, a further DSA should be performed to investigate pathological changes and for a definitive diagnosis. At last, the current therapeutic protocols for BCVI are not entirely applicable to intracranial vascular injury, and appropriate protocols for the treatment of BICI should be selected based on the combination of test results and the actual condition of the patient.

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.

Rosiglitazone ameliorates diffuse axonal injury by reducing loss of tau and up-regulating caveolin-1 expression.

Rosiglitazone up-regulates caveolin-1 levels and has neuroprotective effects in both chronic and acute brain injury. Therefore, we postulated that rosiglitazone may ameliorate diffuse axonal injury via its ability to up-regulate caveolin-1, inhibit expression of amyloid-beta precursor protein, and reduce the loss and abnormal phosphorylation of tau. In the present study, intraperitoneal injection of rosiglitazone significantly reduced the levels of amyloid-beta precursor protein and hyperphosphorylated tau (phosphorylated at Ser(404)(p-tau (S(404))), and it increased the expression of total tau and caveolin-1 in the rat cortex. Our results show that rosiglitazone inhibits the expression of amyloid-beta precursor protein and lowers p-tau (S(404)) levels, and it reduces the loss of total tau, possibly by up-regulating caveolin-1. These actions of rosiglitazone may underlie its neuroprotective effects in the treatment of diffuse axonal injury.

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.

Receptor-associated protein promotes t-PA expression, reduces PAI-1 expression and improves neurorecovery after acute ischemic stroke.

Receptor-associated protein (RAP) is a receptor antagonist that inhibits ligand interactions with the receptors that belong to the low density lipoprotein receptor gene family. The low-density lipoprotein receptor-related protein 1 (LRP1) has a crucial role in regulating tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) expression. Furthermore, the functional balance of these two proteins is directly associated with the initiation and development of cerebral ischemic stroke. In the present study, the effect of RAP post-treatment was investigated in a rat autologous thromboembolic model. The expression and activity of t-PA and PAI-1 were detected and the neurological function was tested. The results suggest that post-treatment with RAP is able to improve neurorecovery after ischemic stroke by decreasing vascular damage and regulating t-PA and PAI-1 expressions. Post-treatment with RAP promotes t-PA expression, suppresses PAI-1 expression, significantly improves functional outcomes and decreases the amount of TUNEL-positive cells. RAP-treated rats show lower intracranial hemoglobin levels and a smaller ischemic zone. In conclusion, post-treatment with RAP regulates t-PA and PAI-1 expressions and thereby contributes to the improvement of functional outcomes after cerebral ischemia. Our findings strongly suggest that RAP may be of value in neurorecovery after stroke.

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.