Incremental Value of Stroke-Induced Structural Disconnection in Predicting Global Cognitive Impairment After Stroke.

BACKGROUND: Poststroke cognitive impairment (PSCI) is highly prevalent in stroke survivors and correlated with unfavorable clinical outcomes. This study aimed to identify the neural substrate of PSCI using atlas-based disconnectome analysis and assess the value of disconnection score, a baseline measure for stroke-induced structural disconnection, in PSCI prediction. METHODS: A multicenter prospective cohort of 676 first-ever patients with acute ischemic stroke was enrolled from 3 independent hospitals in China. Sociodemographic, clinical, and neuroimaging data were collected at acute stage of stroke. Cognitive assessment was performed at 3 months after stroke. Voxel-wise and tract-wise disconnectome analysis were performed to uncover the strategic structural disconnection pattern for global PSCI. Disconnection score was calculated for each participant in leave-one-dataset-out cross-validation. Multivariable logistic regression was performed for the association between disconnection score and PSCI. Prediction models with and without disconnection score were developed, cross-validated, and compared in terms of discrimination and goodness-of-fit. RESULTS: Compared with lesions of non-PSCI, those of PSCI were more likely to have fiber connections with left prefrontal cortex and left deep structures (thalamus and basal ganglia). Disconnection score could predict the risk and severity of PSCI during cross-validation, and was independently associated with PSCI after controlling for all baseline covariates (odds ratio, 1.38 [95% CI, 1.17-1.64]; P<0.001). Incorporating disconnection score into a reference model with 6 known predictors resulted in significant improvement in both discrimination and goodness-of-fit throughout cross-validation. CONCLUSIONS: A strategic structural disconnection pattern centered on left prefrontal cortex, thalamus, and basal ganglia is identified for global PSCI using indirect disconnectome analysis. The baseline disconnection score is independently predictive of PSCI and has significant incremental value to preexisting sociodemographic, clinical, and neuroimaging predictors. REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx; Unique identifier: ChiCTR-ROC-17013993.

Good functional outcome following bilateral external capsule hemorrhage mimicking bilateral basal ganglia hemorrhage in a coma patient.

Simultaneous spontaneous bilateral external capsule hemorrhage is a rare clinical entity with extremely poor outcome. However, knowledge on the effective management of this fatal disease is limited. Herein,we described a case of a 42-year-old man with acute coma and quadriplegia as well as respiratory failure related to the disease. The patient underwent minimally invasive surgery plus local thrombolysis. Consequently, he recovered with satisfactory neurological function recovery on the 180th day of follow-up.

Comparative study on acute management of intracerebral haematoma using local thrombolysis in moyamoya and non-moyamoya patients: a single institution experience.

PURPOSE: Spontaneous intracerebral haemorrhage (ICH) is the main presentation in adults with moyamoya disease (MMD), an unusual clinical entity with a poor prognosis. However, optimal management in the acute stage of ICH in patients with MMD remains a challenge. Since minimally invasive surgery (MIS) plus local thrombolysis has emerged as a promising strategy for ICH, we aimed to describe our experience of performing this procedure in this special population in the acute phase, while focusing on its efficacy and safety. MATERIALS AND METHODS: The medical data of patients with ICH treated with MIS and local thrombolysis between November 2013 and December 2017 were retrospectively reviewed at our institution. MMD was identified based on the angiographic images. The primary outcome was postoperative intracranial rebleeding. The secondary outcomes were 30-day mortality and 6-month outcome graded using the modified Rankin scale (mRS). Logistic regression was applied to explore independent risk factors for the above outcomes. RESULTS: A cohort of consecutive 337 ICH patients was analysed, of whom 14 (4.15%) were diagnosed with MMD. In total, 36 (11.46%) patients experienced postoperative intracranial rehaemorrhage, of which one patient had MMD. No significant difference was found between the patients with and without MMD regarding postoperative rebleeding (9.09% vs. 11.55%, p = 1.000). Additionally, the 30-day mortality of patients with MMD was 21.42% (3/14), which was not significantly different from that of non-MMD patients (10.83%; p = 0.201). Moreover, 53.8% of patients had poor outcomes at the 6-month follow-up among MMD patients, similar to 43.9% of patients without MMD (p = 0.573). The coexistence of MMD failed to show a significant association with postoperative intracranial rebleeding (p = 0.348), 30-day mortality (p = 0.211), or poor outcome at the 6-month follow-up (p = 0.450). CONCLUSION: Our findings suggest that coexistent MMD is not associated with an increased risk of postoperative rebleeding or poor outcome after local thrombolysis for ICH.

Application of kNN and SVM to predict the prognosis of advanced schistosomiasis.

Predictive models for prognosis of small sample advanced schistosomiasis patients have not been well studied. We aimed to construct prognostic predictive models of small sample advanced schistosomiasis patients using two machine learning algorithms, k nearest neighbour (kNN) and support vector machine (SVM) utilising routinely available data under the government medical assistance programme. The predictive models were derived from 229 patients from Xiantao and externally validated by 77 patients of Jiayu, two county-level cities in Hubei province, China. Candidate predictors were selected according to expert opinions and literature reports, including clinical features, sociodemographic characteristics, and medical examinations results. An area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the models' predictive performances. The AUC values were 0.879 for the kNN model and 0.890 for the SVM model in the training set, 0.852 for the kNN model, and 0.785 for the SVM model in the external validation set. The kNN and SVM models can be used to improve the health services provided by healthcare planners, clinicians, and policymakers.

Activation of MC1R with BMS-470539 attenuates neuroinflammation via cAMP/PKA/Nurr1 pathway after neonatal hypoxic-ischemic brain injury in rats.

BACKGROUND: Microglia-mediated neuroinflammation plays a crucial role in the pathogenesis of hypoxic-ischemic (HI)-induced brain injury. Activation of melanocortin-1 receptor (MC1R) has been shown to exert anti-inflammatory and neuroprotective effects in several neurological diseases. In the present study, we have explored the role of MC1R activation on neuroinflammation and the potential underlying mechanisms after neonatal hypoxic-ischemic brain injury in rats. METHODS: A total of 169 post-natal day 10 unsexed rat pups were used. HI was induced by right common carotid artery ligation followed by 2.5 h of hypoxia. BMS-470539, a specific selective MC1R agonist, was administered intranasally at 1 h after HI induction. To elucidate the potential underlying mechanism, MC1R CRISPR KO plasmid or Nurr1 CRISPR KO plasmid was administered via intracerebroventricular injection at 48 h before HI induction. Percent brain infarct area, short- and long-term neurobehavioral tests, Nissl staining, immunofluorescence staining, and Western blot were conducted. RESULTS: The expression levels of MC1R and Nurr1 increased over time post-HI. MC1R and Nurr1 were expressed on microglia at 48 h post-HI. Activation of MC1R with BMS-470539 significantly reduced the percent infarct area, brain atrophy, and inflammation, and improved short- and long-term neurological deficits at 48 h and 28 days post-HI. MC1R activation increased the expression of CD206 (a microglial M2 marker) and reduced the expression of MPO. Moreover, activation of MC1R with BMS-470539 significantly increased the expression levels of MC1R, cAMP, p-PKA, and Nurr1, while downregulating the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-1ß) at 48 h post-HI. However, knockout of MC1R or Nurr1 by specific CRISPR reversed the neuroprotective effects of MC1R activation post-HI. CONCLUSIONS: Our study demonstrated that activation of MC1R with BMS-470539 attenuated neuroinflammation, and improved neurological deficits after neonatal hypoxic-ischemic brain injury in rats. Such anti-inflammatory and neuroprotective effects were mediated, at least in part, via the cAMP/PKA/Nurr1 signaling pathway. Therefore, MC1R activation might be a promising therapeutic target for infants with hypoxic-ischemic encephalopathy (HIE).

Nomograms to predict 2-year overall survival and advanced schistosomiasis-specific survival after discharge: a competing risk analysis.

BACKGROUND: The prognosis of patients with advanced schistosomiasis is poor. Pre-existing prognosis studies did not differentiate the causes of the deaths. The objectives were to evaluate the 2-year overall survival (OS) and advanced schistosomiasis-specific survival (ASS) in patients with advanced schistosomiasis after discharge through competing risk analysis and to build predictive nomograms. METHODS: Data was extracted from a previously constructed database from Hubei province. Patients were enrolled from September 2014 to January 2015, with follow up to January 2017. OS and ASS were primary outcome measures. Nomograms for estimating 2-year OS and ASS rates after discharge were established based on univariate and multivariate Cox regression model and Fine and Gray's model. Their predictive performances were evaluated using C-index and validated in both internal and external validation cohorts. RESULTS: The training cohort included 1487 patients with advanced schistosomiasis. Two-year mortality rate of the training cohort was 8.27% (123/1487). Competing events accounted for 26.83% (33/123). Older age, splemomegaly clinical classification, abnormal serum DBil, AST, ALP and positive HBsAg were significantly associated with 2-year OS. Older age, splemomegaly clinical classification, abnormal serum AST, ALP and positive HBsAg were significantly associated with 2-year ASS. The established nomograms were well calibrated, and had good discriminative ability, with a C-index of 0.813 (95% CI 0.803-0.823) for 2-year OS prediction and 0.834 (95% CI 0.824-0.844) for 2-year ASS prediction. Their predictive performances were well validated in both internal and external validation cohorts. CONCLUSION: The effective predictors of 2-year OS and ASS were discovered through competing risk analysis. The nomograms could be used as convenient predictive tools in clinical practice to guide follow-up and aid accurate prognostic assessment.

Modulation of Self-Separating Molecular Catalysts for Highly Efficient Biomass Transformations.

The energetically viable fabrication of stable and highly efficient solid acid catalysts is one of the key steps in large-scale transformation processes of biomass resources. Herein, the covalent modification of the classical Dawson polyoxometalate (POMs) with sulfonic acids (-SO3 H) is reported by grafting sulfonic acid groups on the POM's surface followed by oxidation of (3-mercaptopropyl)trimethoxysilane. The acidity of TBA6 -P2 W17 -SO3 H (TBA=tetrabutyl ammonium) has been demonstrated by using 31 P NMR spectroscopy, clearly indicating the presence of strong Brønsted acid sites. The presence of TBA counterions renders the solid acid catalyst as a promising candidate for phase transfer catalytic processes. The TBA6 -P2 W17 -SO3 H shows remarkable activity and selectivity, excellent stability, and great substrate compatibility for the esterification of free fatty acids (FFA) with methanol and conversion into biodiesel at 70 °C with >98 % conversion of oleic acid in 20 min. The excellent catalytic performance can be attributed to the formation of a catalytically active emulsion, which results in a uniform catalytic behavior during the reaction, leading to efficient interaction between the substrate and the active sites of the catalyst. Most importantly, the catalyst can be easily recovered and reused without any loss of its catalytic activity owing to its excellent phase transfer properties. This work offers an efficient and cost-effective strategy for large-scale biomass conversion applications.

Primary central nervous system extranodal nasal-type natural killer/T-cell lymphoma with CD20 expression.

We report a unique case of primary CNS extranodal natural killer/T-cell lymphoma (PCNS ENKTCL) with CD20 expression and the monoclonal rearrangement of Ig heavey chain (IgH) gene. Resection specimens were evaluated using HE-stained sections, immunohistochemistry, in situ hybridization and PCR. Histopathologic examination, immunohistochemistry and molecular studies showed the intermediate-sized lymphoma cells expressing CD2, CD3ε, granzyme B, TIA-1, CD20 and Epstein-Barr virus-encoded RNA, with germline T-cell receptor gene and the monoclonal rearrangement of IgH gene. Clinicopathologic and radiographic evaluation indicated the lesion was of exclusive left cerebellar localization. Thus, PCNS ENKTCL with the CD20 expression was diagnosed. ENKTCL with both CD20-positive expression and the monoclonal rearrangement of IgH gene may be mistaken for B-cell lymphoma; thus, the comprehensive evaluation of histomorphology, more extensive immunoprofiles and molecular studies is essential to reach the correct diagnosis. The rare PCNS ENKTCL shows a highly aggressive nature and a poorer prognosis.

Baicalein inhibits α-synuclein oligomer formation and prevents progression of α-synuclein accumulation in a rotenone mouse model of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease. α-Synuclein (α-syn) oligomers play a critical role in the progression of PD. Baicalein, a typical flavonoid compound, can inhibit the formation of the α-syn oligomers, and disaggregate existing α-syn oligomers in vitro. However, whether baicalein could inhibit or disaggregate α-syn oligomers in vivo has not been investigated. Therefore, this study was designed to investigate the inhibitory effects of baicalein on α-syn oligomers in vivo and to explore the possible mechanisms of such inhibition. A chronic PD mouse model was created by continuous intragastric administration of rotenone (5mg/kg, 12weeks). Baicalein (100mg/kg) was intraperitoneally injected from 7week to 12week. Our result showed that the amount of α-syn, changes in the levels of the striatal neurotransmitters, and the behavioral changes found in the chronic PD mouse model were prevented after the baicalein injections. Although baicalein did not decrease α-syn mRNA expression, α-syn oligomers were significantly decreased in the ileum, thoracic spinal cord, and midbrain. Furthermore, transmission electron microscopy analysis showed that baicalein could prevent α-syn monomers from the oligomer formation in vitro. Taken together, these results suggest that baicalein could prevent the progression of α-syn accumulation in PD mouse model partly by inhibiting formation of the α-syn oligomers.

Extensive basal ganglia hematomas treated by local thrombolysis versus conservative management - a comparative retrospective analysis.

OBJECTIVES: Single-target puncture plus catheter insertion into the clot is a routine step in hematoma aspiration and local thrombolysis for spontaneous intracerebral haemorrhage (ICH). However, multiple-target puncture of this procedure may imply faster hematoma reduction for large-area ICH. We retrospectively examined the outcomes after clot aspiration plus local thrombolysis with single-/double-target and conservative therapy for extensive basal ganglic hematomas. METHODS: A case note review was conducted on a consecutive series of ICH patients in a single centre with huge basal ganglia hematomas who underwent clots aspiration and thrombolysis or pure medical therapy. We analysed the clinical presentation, radiological features and treatment outcomes of ICH patients in single-target group, double-target group and conservative group. RESULTS: A total of 92 ICH cases were included in this study. At the post-treatment assessment, the average level by hematoma size in single-target and double-group was respectively smaller than that in the conservative group (20.61 ml vs. 15.75 ml vs 60.53 ml, p < 0.01). The 30-day case fatality rate in conservative group was respectively significantly higher than that in single-target and double-target groups (50% vs. 14.70% vs. 20.59%, p < 0.01). At the time of 6-month follow-up, the proportion of good survival in conservative group was respectively remarkably less than that in single- and double-target group (29.17% vs.64.71% vs. 67.65%, p < 0.01). But no difference was detected with respect to 30-day mortality or long-time outcome between the two micro-invasive groups (p = 0.53 and 0.798, respectively). CONCLUSION: Our data suggested for the massive basal ganglia hematomas, clot aspiration and thrombolysis can improve the short- and long-term prognosis compared with the pure conservative therapy. But, no evidence was found to demonstrate double-target of this procedure to be more effective than single-target to improve the outcome.

Effects of endovascular therapy on acute ischemic stroke:An updated meta-analysis of randomized controlled trials.

OBJECTS: To clarify the effects of endovascular therapy (ET) for acute ischemic stroke (AIS) patients, we conducted an updated meta-analysis using data from randomized controlled trials (RCTs). METHODS: We searched major electronic databases for RCTs comparing ET with intravenous thrombolysis (IVT) or other standard treatments for AIS patients. Eligible and high-quality RCTs were included in the meta-analysis. The overall estimates were demonstrated as an odds ratio (OR) with 95% confidence interval (CI) and P value. RESULTS: Thirteen high-quality trials met the inclusion criteria and were analyzed. Patients treated by ET were more likely to have good functional outcomes (OR, 1.70; 95% CI, 1.32-2.19; P< 0.0001) and lower mortality rates (OR, 0.77; 95% CI, 0.60-0.98; P = 0.03) at 90 days than patients treated by IVT or standard treatment. There was no significant difference in the rate of symptomatic intracerebral hemorrhage [sICH] (OR, 1.18; 95% CI, 0.73-1.91; P = 0.50). CONCLUSIONS: ET is superior to both IVT and standard treatment in providing functional improvement and reducing the mortality rate at 90 days, while not increasing the risk of sICH for the treatment of AIS.

Lower serum uric acid levels in cerebral amyloid angiopathy: a pilot study.

Cerebral amyloid angiopathy (CAA) is a common degenerative disease presenting intracerebral hemorrhage (ICH) in older people. Uric acid (UA) is a natural antioxidant, and may have a beneficial role in neurodegenerative diseases. Nevertheless, the role of UA in CAA remains unknown. In the present study, we compared serum UA levels in CAA-associated ICH patients (n = 82) and age/sex-matched controls (n = 82). Serum UA levels in possible CAA were significantly decreased when compared with healthy controls (232.68 ± 77.70 vs. 309.42 ± 59.83 µmol/L; p < 0.001). Furthermore, UA levels in patients clinically diagnosed as probable CAA were significantly lower than those in patients diagnosed as possible CAA (193.06 ± 56.98 vs. 232.68 ± 77.70 µmol/L; p = 0.014). These differences were still significant after adjusting for renal function and dyslipidemia (p < 0.001 and p = 0.002, respectively). However, there were no associations between serum UA levels and the distribution of hemorrhagic lesion, as well as neurological impairment. Our observations indicate that serum UA levels were decreased in CAA patients. UA might play a neuroprotective role in CAA and serve as a potential biomarker for reflecting the severity of Aß deposition.

No exacerbation of perihematomal edema with intraclot urokinase in patients with spontaneous intracerebral hemorrhage.

BACKGROUND: Perihematomal edema (PHE) can worsen patient outcomes after spontaneous intracerebral hemorrhage (ICH). Minimally invasive surgery (MIS) in combination with thrombolytic removal of hematoma has been proven to be a promising treatment strategy. However, preclinical studies have suggested that intraclot thrombolysis may exacerbate PHE after ICH. Herein, we investigated the effects of MIS and urokinase on PHE. METHODS: ICH patients were retrospectively identified from our institutional ICH database. Computerized volumetric analysis was applied to assess changes in both ICH and PHE volumes using computed tomographic (CT) scans of T1 (pre-MIS) and T2 (post-MIS) time points. Relative PHE (rPHE) was calculated as a ratio of PHE and T1 ICH volume. RESULTS: Data from 60 MIS plus urokinase (MIS + U), 20 MIS aspiration only (MO), and 30 control patients were analyzed. The ICH volume, PHE volume and rPHE on T2 CT in both MIS + U and MO groups significantly decreased as compared with the control group (ICH volume, 13.7 ± 5.7 ml, 17.0 ± 10.5 ml vs. 30.5 ± 10.3 ml, P < 0.01; PHE volume, 36.5 ± 18.9 ml, 32.2 ± 17.5 ml vs. 45.4 ± 16.0 ml, P < 0.01; rPHE, 0.9 ± 0.4, 0.8 ± 0.4 vs.1.4 ± 0.5, P < 0.01). Between the MIS + U and MO groups, the ICH volume, PHE volume and rPHE at T2 trended towards similarity, but was not significant (P = 0.09, P = 0.40, P = 0.43). Furthermore, we found a significant correlation between the percent of ICH removal and PHE reduction (r = 0.59, P < 0.01). There was no correlation between the cumulative dose of urokinase and either T2 PHE volume (r = 0.19; P = 0.16) or T2 rPHE (r = -0.12; P = 0.37). CONCLUSIONS: Hematoma evacuation using MIS leads to a significant reduction in PHE. Furthermore, the use of urokinase does not exacerbate PHE, making its hypothesized proedematous effects unlikely when the thrombolytic is administered directly into the clot.

Pneumocephalus following the minimally invasive hematoma aspiration and thrombolysis for ICH.

INTRODUCTION: The objective of this study was to clarify whether pneumocephalus occurred and affected the outcome following minimally invasive hematoma aspiration and thrombolysis for intracerebral hemorrhage (ICH). MATERIALS AND METHODS: A prospective case note review on all ICH patients treated with the micro-invasive procedure presenting to our division from 2006 to 2011 was conducted. Demographic, clinical, and outcome data were documented; head CT scans were applied postoperatively to identify the intracranial air collection. The ICH victims with pneumocephalus were included into Group A and the others into Group B. A multi-variant analysis was performed between Groups A and B to examine the effect of pneumocephalus on the prognosis. RESULTS: Data were collected on a total of 134 cases in this study, among whom 72.38% developed pneumocephalus postoperatively. No significant difference was demonstrated in terms of the preoperative and postoperative hematoma volume, Glasgow Coma Scale (GCS) score, middle line shift (MLS), and 30-day mortality rate between Groups A and B, respectively. Moreover, the long-term outcome rated by GCS of these two groups was also similar. Logistic regression analysis indicated double-needle puncture be an independent risk factor for both postoperative pneumocephalus (OR, 2.478; 95% CI, 1.010-6.080; P = 0.045) and its degree (OR, 11.84; 95%CI, 4.141-30.208; P < 0.001). CONCLUSION: The present study shows that pneumocephalus is common following the minimally invasive hematoma aspiration and thrombolysis for ICH but may not affect the outcome. And double-needle puncture may be the risk factor for pneumocephalus.

Intraclot recombinant tissue-type plasminogen activator reduces perihematomal edema and mortality in patients with spontaneous intracerebral hemorrhage.

The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10-16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39-0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.

Delayed recanalization reduced neuronal apoptosis and neurological deficits by enhancing liver-derived trefoil factor 3-mediated neuroprotection via LINGO2/EGFR/Src signaling pathway after middle cerebral artery occlusion in rats.

Delayed recanalization at days or weeks beyond the therapeutic window was shown to improve functional outcomes in acute ischemic stroke (AIS) patients. However, the underlying mechanisms remain unclear. Previous preclinical study reported that trefoil factor 3 (TFF3) was secreted by liver after cerebral ischemia and acted a distant neuroprotective factor. Here, we investigated the liver-derived TFF3-mediated neuroprotective mechanism enhanced by delayed recanalization after AIS. A total of 327 male Sprague-Dawley rats and the model of middle cerebral artery occlusion (MCAO) with permanent occlusion (pMCAO) or with delayed recanalization at 3 d post-occlusion (rMCAO) were used. Partial hepatectomy was performed within 5 min after MCAO. Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2) siRNA was administered intracerebroventricularly at 48 h after MCAO. Recombinant rat TFF3 (rr-TFF3, 30 µg/Kg) or recombinant rat epidermal growth factor (rr-EGF, 100 µg/Kg) was administered intranasally at 1 h after recanalization, and EGFR inhibitor Gefitinib (75 mg/Kg) was administered intranasally at 30 min before recanalization. The evaluation of outcomes included neurobehavior, ELISA, western blot and immunofluorescence staining. TFF3 in hepatocytes and serum were upregulated in a similar time-dependent manner after MCAO. Compared to pMCAO, delayed recanalization increased brain TFF3 levels and attenuated brain damage with the reduction in neuronal apoptosis, infarct volume and neurological deficits. Partial hepatectomy reduced TFF3 levels in serum and ipsilateral brain hemisphere, and abolished the benefits of delayed recanalization on neuronal apoptosis and neurobehavioral deficits in rMCAO rats. Intranasal rrTFF3 treatment reversed the changes associated with partial hepatectomy. Delayed recanalization after MCAO increased the co-immunoprecipitation of TFF3 and LINGO2, as well as expressions of p-EGFR, p-Src and Bcl-2 in the brain. LINGO2 siRNA knockdown or EGFR inhibitor reversed the effects of delayed recanalization on apoptosis and brain expressions of LINGO2, p-EGFR, p-Src and Bcl-2 in rMCAO rats. EGFR activator abolished the deleterious effects of LINGO2 siRNA. In conclusion, our investigation demonstrated for the first time that delayed recanalization may enhance the entry of liver-derived TFF3 into ischemic brain upon restoring blood flow after MCAO, which attenuated neuronal apoptosis and neurological deficits at least in part via activating LINGO2/EGFR/Src pathway.

Spontaneous intracerebral hemorrhage in CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary small vascular disease and its mainly clinical manifestations are ischemic events. Spontaneous intracerebral hemorrhage (ICH) involvement in patients with CADASIL is extremely uncommon. CASE REPORT: A 46-year-old normotensive Chinese man developed a large hematoma in the left basal ganglia after he was diagnosed with CADASIL 2 months ago, the patient did not take any antithrombotics. Susceptibility weighted imaging at pre-ICH showed multiple cerebral microbleeds (CMBs) in the bilateral basal ganglia. He experienced migraine at about 10 months post-ICH. To our knowledge, this is the first report of ICH in CADASIL patients with Arg90Cys mutation in exon 3. DISCUSSION AND CONCLUSIONS: ICH should be considered when evaluating new attacks in CADASIL patients. Thus, MRI screening for CMBs might be helpful in predicting the risk of ICH and guiding antithrombotic therapy. In addition, strict control of hypertension and cautious use of antithrombotics may be important in this context.

Laser-Triggered High Graphitization of Mo2C@C: High Rate Performance and Excellent Cycling Stability as Anode of Lithium Ion Batteries.

Fast electron/ion transport and cycling stability of anode materials are key factors for achieving a high rate performance of battery materials. Herein, we successfully fabricated a carbon-coated Mo2C nanofiber (denoted as laser Mo2C@C) as the lithium ion battery anode material by laser carbonization of PAN-PMo12 (PAN = Polyacrylonitrile; PMo12 = H3PMo12O40). The highly graphitized carbon layer in laser Mo2C@C effectively protects Mo2C from agglomeration and flaking while facilitating electron transfer. As such, the laser Mo2C@C electrode displays an excellent electrochemical stability under 5 A g-1, with a capacity up to 300 mA h g-1 after 3000 cycles. Furthermore, the extended X-ray absorption fine structure results show the existence of some Mo vacancies in Mo2C@C. Density functional theory calculations further prove that such vacancies make the defective Mo2C@C composites energetically more favorable for lithium storage in comparison with the intact Mo2C.

Caspase-1: A Promising Target for Preserving Blood-Brain Barrier Integrity in Acute Stroke.

The blood-brain barrier (BBB) acts as a physical and biochemical barrier that plays a fundamental role in regulating the blood-to-brain influx of endogenous and exogenous components and maintaining the homeostatic microenvironment of the central nervous system (CNS). Acute stroke leads to BBB disruption, blood substances extravasation into the brain parenchyma, and the consequence of brain edema formation with neurological impairment afterward. Caspase-1, one of the evolutionary conserved families of cysteine proteases, which is upregulated in acute stroke, mainly mediates pyroptosis and compromises BBB integrity via lytic cellular death and inflammatory cytokines release. Nowadays, targeting caspase-1 has been proven to be effective in decreasing the occurrence of hemorrhagic transformation (HT) and in attenuating brain edema and secondary damages during acute stroke. However, the underlying interactions among caspase-1, BBB, and stroke still remain ill-defined. Hence, in this review, we are concerned about the roles of caspase-1 activation and its associated mechanisms in stroke-induced BBB damage, aiming at providing insights into the significance of caspase-1 inhibition on stroke treatment in the near future.

Piezo1 Mediates Inflammation in Balloon-inflated Rat Brain and its Bidirectional Mechanosensitivity.

BACKGROUND: Brain injury after intracerebral hemorrhage is extremely complicated, and the exact mechanism remains puzzling. Piezo1, a novel mammalian mechanosensitive ion channel, has been identified to play important roles in several pathologic and physiologic procedures that involve cellular mechanotransduction. However, the role of Piezo1 in hematoma compression after intracerebral hemorrhage is still unclear. MATERIALS AND METHODS: In the present study, we established a balloon-inflated brain model based on an adult male rat mimicking the pure mechanical compression of a hematoma. Then the behavioral assessment (Garcia Scale) was taken to observe the syndrome after "hematoma". Western blotting and immunofluorescence were applied to detect Piezo1 expression around lesions in rat brains. ELISA was used for quantitative analysis of inflammation factors. A statistical significance was confirmed as P value<0.05. RESULTS: Balloon compression lesions were detected in the basal ganglia region of the brain, resulting in abnormal behaviors and a significant increase in the expression of Piezo1 and proinflammatory cytokines. GsMTx4, an antagonist of Piezo1, reversed these effects. Additionally, the balloon deflation time affected behavioral function and the levels of Piezo1 and proinflammatory cytokines. CONCLUSION: These results establish the first in vivo evidence for the role of Piezo1 in blood-brain neuroinflammation after hematoma compression. Piezo1 showed "bidirectional mechanosensitivity" and therefore is a potential therapeutic target for the treatment of intracerebral hemorrhage.