Blood Pressure Fluctuation During 72 Hours After Endovascular Therapy and Prognosis in Acute Ischemic Stroke Patients.

PURPOSE: Our study aimed to investigate the relationship between fluctuations in different blood pressure (BP) components within 72 hours following endovascular therapy (EVT) and the prognosis of acute ischemic stroke (AIS) patients. METHODS: This prospective multicenter study included 283 AIS patients who underwent EVT and had available BP data. The primary outcome was the ordinal modified Rankin Scale (mRS) score evaluated at 90 days. The secondary outcome was a combination of death and major disability, defined as an mRS score of 3 to 6 within 3 months. RESULTS: After adjusting for imbalanced variables, the highest tertile of systolic blood pressure (SBP) fluctuation had an odds ratio (OR) of 1.747 (95% confidence interval [CI]=1.031-2.961; p for trend=0.035) for the primary outcome and 1.889 (95% CI=1.015-3.516; p for trend=0.039) for the secondary outcome, respectively. Fluctuations in diastolic blood pressure (DBP) (OR=1.914, 95% CI=1.134-3.230, p for trend=0.015) and mean arterial pressure (MAP) (OR=1.759, 95% CI=1.026-3.015, p for trend=0.039) were only associated with the primary outcome. The multivariate-adjusted restricted cubic spline analyses supported these findings. Furthermore, the fluctuations in both SBP and MAP exhibited the significant discriminatory capability in predicting the prognosis, comparable to their mean values. CONCLUSION: Our study revealed that larger fluctuations in SBP, DBP, and MAP within 72 hours after EVT were associated with a higher risk of poor clinical outcomes within 3 months in AIS patients. Controlling BP fluctuations may be valuable for improving the prognosis in patients undergoing EVT. CLINICAL IMPACT: How will this change clinical practice?It provides physicians a new approach to directly monitor BP fluctuations over an extended observation period in AIS patients after EVT in routine clinical practice.What does it mean for the clinicians?These results underscore the importance of giving equal attention to controlling long-term BP fluctuations, in addition to managing mean BP, as a means to improve the prognosis of AIS patients after EVT.What is the innovation behind the study?This study systematically evaluated the association between fluctuations in different blood pressure components and clinical outcomes in AIS patients over an extended period following EVT.

Deubiquitylating Enzyme OTUB1 Facilitates Neuronal Survival After Intracerebral Hemorrhage Via Inhibiting NF-κB-triggered Apoptotic Cascades.

The deubiquitylase OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) has been implicated in the pathogenesis of various human diseases. However, the molecular mechanism by which OTUB1 participates in the pathogenesis of intracerebral hemorrhage (ICH) remains elusive. In the present study, we established an autologous whole blood fusion-induced ICH model in C57BL/6 J mice. We showed that the upregulation of OTUB1 contributes to the attenuation of Nuclear factor kappa B (NF-κB) and its downstream apoptotic signaling after ICH. OTUB1 directly associates with NF-κB precursors p105 and p100 after ICH, leading to attenuated polyubiquitylation of p105 and p100. Moreover, we revealed that NF-κB signaling was modestly activated both in ICH tissues and hemin-exposed HT-22 neuronal cells, accompanied with the activation of NF-κB downstream pro-apoptotic signaling. Notably, overexpression of OTUB1 strongly inhibited hemin-induced NF-κB activation, whereas interference of OTUB1 led to the opposite effect. Finally, we revealed that lentiviral transduction of OTUB1 markedly ameliorated hemin-induced apoptotic signaling and HT-22 neuronal death. Collectively, these findings suggest that the upregulation of OTUB1 serves as a neuroprotective mechanism in antagonizing neuroinflammation-induced NF-κB signaling and neuronal death, shed new light on manipulating intracellular deubiquitylating pathways as novel interventive approaches against ICH-induced secondary neuronal damage and death.

Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson's disease.

Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson's disease using 6-hydroxydopamine. When SH-SY5Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson's disease and in a mouse model of Parkinson's disease. Next, we pretreated cell models of Parkinson's disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson's disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor down-regulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase (PI3K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulin-like growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson's disease treatment.

Development and validation of a RASS-related nomogram to predict the in-hospital mortality of neurocritical patients: a retrospective analysis based on the MIMIC-IV clinical database.

BACKGROUND: Richmond agitation-sedation scale (RASS) is a simple and widely used tool for evaluating sedation and agitation in adult ICU patients. Early deep sedation has been shown to be an important independent predictor of death, however, studies on the role of RASS in the prognostic assessment of neurocritical patients are lacking. The purpose of this study was to investigate the relationship between RASS and in-hospital mortality in neurocritical patients, and to develop and validate an effective predictive model based on this. METHODS: This was a retrospective study of neurocritical patients from a large clinical database. A total of 2651 patients were collected, including general demographic characteristics, past medical history, biochemical test data and physical examination within 24 h of admission, and related medical records. Univariate and multivariate logistic regression analyses were used to screen out significant variables. Finally, 11 significant predictors were included into the logistic regression to establish the nomogram. RESULTS: The area under the curve (AUC) of the nomogram was 0.9087(0.8950-0.9224) and the corrected c index was 0.9043, which gave the model better discriminatory ability compared with critical care related scales, such as SOFA and SAPSII scores. Besides, tools including calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to verify that the model had good discrimination, calibration, and clinical applicability. CONCLUSIONS: RASS score was an independent prognostic predictor of in-hospital death in neurocritical patients, and patients who are deeply sedated have a worse prognosis. RASS-related nomogram could be applied to predict the prognosis of neurocritical patients and to take effective intervention measures in early stage.

Platelet count and clinical outcomes among ischemic stroke patients with endovascular thrombectomy in DIRECT-MT.

OBJECTIVES: The prognostic role of baseline platelet count (PLT) in acute ischemic stroke patients with large vessel occlusion undergoing endovascular thrombectomy is unclear. Whether PLT modifies alteplase treatment effect on clinical outcome in those patients is also uncertain. METHODS: We derived data from a multicenter randomized clinical trial (DIRECT-MT) comparing intravenous alteplase before endovascular treatment vs. endovascular treatment only. The 654 patients with available PLT data were included. Primary outcome was the ordinal modified Rankin Scale (mRS) score evaluated at 90 days. We also assessed various secondary and safety outcomes. RESULTS: After adjusting for confounding factors, patients in the top tertile of PLT had a significantly lower risk of a worse shift in the distribution of mRS score (Odds Ratio: 0.671, 95% Confidence Interval: 0.473-0.953, p for trend=0.025), major disability and death (Odds Ratio: 0.617, 95% Confidence Interval: 0.393-0.97, p for trend=0.037) as well as death (Odds Ratio: 0.544, 95% Confidence Interval: 0.313-0.947, p for trend=0.031), respectively, compared with the bottom one. Among patients in the bottom tertile of PLT, combination therapy was associated with a better imaging outcome of eTICI score of 2b, 2c or 3 on final angiogram (Odds Ratio: 3.23, 95% Confidence Interval: 1.49-7.002) with a marginally significant interaction effect. CONCLUSIONS: Participants with higher baseline PLT had a decreased risk of poor functional outcomes. Low baseline PLT modified alteplase treatment effect on the eTICI score on final angiogram. Combination therapy was beneficial for patients with low baseline PLT to have a better reperfusion status.

Schwann cells differentiated from skin-derived precursors provide neuroprotection via autophagy inhibition in a cellular model of Parkinson's disease.

Autophagy has been shown to play an important role in Parkinson's disease. We hypothesized that skin-derived precursor cells exhibit neuroprotective effects in Parkinson's disease through affecting autophagy. In this study, 6-hydroxydopamine-damaged SH-SY5Y cells were pretreated with a culture medium containing skin-derived precursors differentiated into Schwann cells (SKP-SCs). The results showed that the SKP-SC culture medium remarkably enhanced the activity of SH-SY5Y cells damaged by 6-hydroxydopamine, reduced excessive autophagy, increased tyrosine hydroxylase expression, reduced α-synuclein expression, reduced the autophagosome number, and activated the PI3K/AKT/mTOR pathway. Autophagy activator rapamycin inhibited the effects of SKP-SCs, and autophagy inhibitor 3-methyladenine had the opposite effect. These findings confirm that SKP-SCs modulate the PI3K/AKT/mTOR pathway to inhibit autophagy, thereby exhibiting a neuroprotective effect in a cellular model of Parkinson's disease. This study was approved by the Animal Ethics Committee of Laboratory Animal Center of Nantong University (approval No. S20181009-205) on October 9, 2018.

circSKA3 acts as a sponge of miR-6796-5p to be associated with outcomes of ischemic stroke by regulating matrix metalloproteinase 9 expression.

BACKGROUND AND PURPOSE: This study was undertaken to screen the circular RNAs (circRNAs) influencing matrix metalloproteinase 9 (MMP9) through the competing endogenous RNA (ceRNA) network and evaluate the prognostic value of these circRNAs for acute ischemic stroke. METHODS: A total of 220 ischemic stroke patients and 62 healthy subjects were included in this study. RNA was isolated from blood collected in PAXgene tubes. Illumina sequencing, quantitative real-time polymerase chain reaction (qRT-PCR) validation, and luciferase reporter assay were explored to construct and verify the existence of a circRNA-microRNA (miRNA)-matrix metalloproteinase-9 (MMP9) network. The 215 ischemic stroke patients were recruited in a prognostic cohort. They were prospectively followed up for 3 months after stroke onset, and a poor functional outcome was defined as a major disability or death. RESULTS: After Illumina sequencing, six circRNAs were predicted to bind miRNAs and then regulate MMP9 messenger RNA (mRNA). qRT-PCR showed that only circSKA3 was significantly increased in ischemic stroke patients compared to healthy controls and positively associated with MMP9 mRNA expression. Luciferase reporter assay further verified a direct interaction between circSKA3, MMP9, and hsa-miR-6796-5p. Patients in the top tertile of circSKA3 had a 2.672-fold (p < 0.05) risk of poor functional outcome, compared with those in the bottom tertile (p for trend = 0.016). The outcome was predicted by circSKA3 with area under the receiver operating characteristic curve at 0.614 (p = 0.004). CONCLUSIONS: circSKA3 functioned as a ceRNA for hsa-miR-6796-5p to aggravate the progression of ischemic stroke via targeting MMP9. Baseline circSKA3 was positively associated with poor outcomes of ischemic stroke. circSKA3 may be a potential biomarker or therapeutic target in ischemic stroke.

Study of the pathology and the underlying molecular mechanism of tissue injury around hematoma following intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) refers to hemorrhage caused by spontaneous rupture of blood vessels in the brain. Brain injury due to ICH leads to catastrophic effects resulting from the formation of hematoma and oxidative stress caused by components of lysed erythrocytes. However, not all neurons in the area surrounding the hematoma die immediately: A number of neurons remain in a critical, but reversible, state; however, the genes involved in this critical state remain poorly understood. Gene chip technology was used identify changes in the area surrounding the hematoma associated with the upregulation of 210 and downregulation of 173 genes. Gene Ontology functional annotation revealed changes in the gene expression profile in the peripheral region of hematoma following ICH, which were primarily associated with the external stimulation received by the organism, the transmission of harmful information to the cell through the transport of cell membrane proteins, and the regulation of a series of biological processes. Protein interaction network analysis revealed that 11 up­[secreted phosphoprotein 1, dual specificity phosphatase 9, catechol­O­methyltransferase, BAR/IMD domain­containing adaptor protein 2­like 1, plakophilin 2, homer scaffold protein 3, ret proto­oncogene (RET), KIT proto­oncogene, receptor tyrosine kinase, hepsin, connector enhancer of kinase suppressor of Ras 2 and kalirin RhoGEF kinase] and four downregulated genes (transcription factor AP­2ß, peptidylprolyl isomerase A, SHOC2 leucine rich repeat scaffold protein and synuclein α) may serve a significant role in the area around hematoma following ICH. Reverse transcription­quantitative PCR was used to verify that these genes were differentially expressed in the ICH compared with the control group. Causal network analysis suggested that the Achaete­scute homolog 1­RET signaling axis served a key role in the repair of nerve injury in the peripheral region of hematoma following ICH. Additionally, in vivo experiments revealed that RET expression was upregulated and co­localized with neurons. Taken together, these results suggested that the changes in the gene expression profile in the area around hematoma following ICH were primarily associated with the repair of damage caused to the nervous system.

PGE1 triggers Nrf2/HO-1 signal pathway to resist hemin-induced toxicity in mouse cortical neurons.

BACKGROUND: Prostaglandin E1 (PGE1) exerts various pharmacological effects such as membrane stabilization, anti-inflammatory functions, vasodilation, and platelet aggregation inhibition. We have previously demonstrated that PGE1 has a beneficial impact on patients suffering from intracerebral hemorrhage (ICH). The related mechanism underlying PGE1's beneficial effect on ICH treatment needs further exploration. METHODS: The present study elucidates the mechanism of PGE1 on ICH treatment using a neuronal apoptosis model in vitro. The mouse primary cortical neurons were pretreated with different concentrations of PGE1, followed by the treatment with hemin, the main catabolite in whole blood, to mimic the clinical ICH. RESULTS: Comparing with the vehicle-treated group, PGE1 prevented cultured cortical neurons from the accumulation of inhibited intracellular levels of reactive oxygen species (ROS), amelioration of mitochondrial membrane potential, and hemin-induced apoptosis. The reduction of ROS and apoptosis were associated with the up-regulation of Heme oxygenase-1 (HO-1) expression. Knockdown of nuclear transcription factor erythroid 2-related factor (Nrf2) by siRNA attenuated the upregulation of HO-1 as well as the protective effect of PGE1. CONCLUSIONS: Our work suggests that the Nrf2/HO-1 molecular pathway may play a crucial role in treating ICH patients with PGE1 and may represent novel molecular targets, resulting in discovering new drugs for ICH treatment.

Intracarotid Transplantation of Skin-Derived Precursor Schwann Cells Promotes Functional Recovery After Acute Ischemic Stroke in Rats.

Purpose: Skin-derived Precursor Schwann cells (SKP-SCs) have been reported to provide neuroprotection for the injured and dysmyelinated nervous system. However, little is known about SKP-SCs on acute ischemic stroke (AIS). We aimed to explore the efficacy and the potential mechanism of action of SKP-SCs on AIS in a rat ischemic stroke model. Methods: Adult male Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) for 1.5 h on Day 0 and subsequently received an intracarotid injection of 2 × 106 green fluorescent protein (GFP) -labeled SKP-SCs or phosphate buffered saline (PBS) during reperfusion. Neurological function was assessed by behavioral tests on Days 1, 4, 7, 14, and 28. In a satellite cohort, rat brains were harvested and infarct volume was measured with 2,3,5-triphenyltetrazolium chloride (TTC) staining on Days 1 and 7, and migration and survival of SKP-SCs in the brain were traced by monitoring green fluorescence at 6 and12 h on Day 0, and on Days 1, 4, 7, 14, and 28. Histopathology and immunofluorescence staining were used to analyze the morphology, survival and apoptosis of neurons. Additionally, in an in vitro SKP-SC co-culture model using fetal rat primary cortical neurons underwent oxygen glucose deprivation/reoxygenation (OGD/R), Western blot was used to detect the expression of apoptosis indicators including activated caspase-3, Bax, and Bcl-2. TUNEL staining was used to count apoptotic cells. Results: Intracarotid transplantation of SKP-SCs effectively migrated to the periinfarct area and survived for at least 4 weeks. Transplanted SKP-SCs inhibited neuronal apoptosis, reduced infarct volume, and improved neurological recovery in the MCAO rats. Moreover, in vitro data showed that SKP-SCs treatment inhibited OGD/R-induced neuronal apoptosis and promoted survival of the cultured primary cortical neurons. Conclusions: Intracarotid transplantation of SKP-SCs promoted functional recovery in the rat AIS model and possesses the potential to be further developed as a novel therapy to treat ischemic stroke in humans.

Effects of homocysteine-induced endoplasmic reticulum protein on endoplasmic reticulum stress, autophagy, and neuronal apoptosis following intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is defined as bleeding into the brain parenchyma with a high mortality and morbidity rate. Unfortunately, it remains an unresolved medical problem. Therefore, it is necessary to find ways to reduce cellular apoptosis after ICH. Homocysteine-induced endoplasmic reticulum protein (HERP), a 54 kD transmembrane protein, is an early stress response protein encoded by ubiquitin-like domain member 1 (Herpud1) gene. In the present work, our group investigated the role of HERP after ICH and hemin stimulation, HERP expression was examined in mouse and primary cortical neurons after ICH and hemin stimulation by western blot and Immunofluorescent labeling. Using shRNA-HERP plasmid and recombinant adenovirus, we also investigated how HERP affected neuronal apoptosis after ICH and hemin stimulation. In addition, behavioral evaluation was used to ensure our models' success. In vivo and vitro studies, the expression of HERP was increased following ICH and hemin-exposed primary cortical neurons. HERP depletion activated the endoplasmic reticulum (ER) stress pathway and apoptosis in hemin-exposed primary cortical neurons, but inhibited autophagy in hemin-exposed primary cortical neurons. Overexpression of HERP inhibited the ER stress pathway and apoptosis, but activated autophagy in hemin-exposed primary cortical neurons. Consequently, we confirm that HERP plays a protective role in ICH model.

RECO Flow Restoration Device Versus Solitaire FR With the Intention for Thrombectomy Study (REDIRECT): a prospective randomized controlled trial.

OBJECTIVE: The RECO flow restoration (FR) device is a new stent retriever designed for rapid flow restoration in acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). Here, the authors compared the efficacy and safety of the RECO device with the predicate Solitaire FR stent retriever. METHODS: The RECO Flow Restoration Device Versus Solitaire FR With the Intention for Thrombectomy Study (REDIRECT) was a multicenter, prospective, open randomized controlled trial. Patients with acute LVO at 7 Chinese stroke centers participated in the study. The primary efficacy endpoint was defined as a modified thrombolysis in cerebral infarction (mTICI) reperfusion grade ≥ 2 within three passes. The primary safety endpoint comprised any serious adverse device effect, symptomatic intracerebral hemorrhage (sICH), and any serious adverse event (SAE; defined as cerebral palsy or death) within 24 hours after the procedure. The secondary efficacy endpoints consisted of functional independence (modified Rankin Scale score 0-2), procedure duration, and 90-day all-cause mortality. RESULTS: Between January 2014 and August 2016, 67 patients were randomly allocated to the RECO group and 69 patients to the Solitaire FR group. The primary efficacy endpoint (mTICI grade ≥ 2 within three passes) was similar in the two treatment groups (91% vs 87%, respectively, p = 0.5861), and the rate of reperfusion with an mTICI grade 2b/3 was 87% versus 75% (p = 0.1272). There were no serious adverse device effects in any patient. The rates of sICH (1.5% vs 7.2%, p = 0.1027) and SAEs (6.0% vs 1.4%, p = 0.2050) within 24 hours after the procedure were similar in the two treatment groups. There was no significant difference in the rate of functional independence (63% vs 46%, p = 0.0609) or 90-day all-cause mortality (13% vs 23%, p = 0.1848) or in procedure duration (85.39 ± 47.01 vs 89.94 ± 53.34 minutes, p = 0.5986) between the two groups. CONCLUSIONS: The RECO stent retriever is effective and safe as a mechanical thrombectomy device for AIS due to LVO. Clinical trial registration no.: NCT01983644 (clinicaltrials.gov).

Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke.

BACKGROUND: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy. METHODS: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area. RESULTS: Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group. CONCLUSIONS: In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

Skin-derived precursor Schwann cells protect SH-SY5Y cells against 6-OHDA-induced neurotoxicity by PI3K/AKT/Bcl-2 pathway.

Skin-derived precursors (SKPs) are self-renewing and pluripotent adult stem cell sources that have been successfully obtained and cultured from adult tissues of rodents and humans. Skin-derived precursor Schwann cells (SKP-SCs), derived from SKPs when cultured in a neuro stromal medium supplemented with some appropriate neurotrophic factors, have been reported to play a neuroprotective effect in the peripheral nervous system. This proves our previous studies that SKP-SCs' function to bridge sciatic nerve gap in rats. However, the function of SKP-SCs in Parkinson disease (PD) remains unknown. This study was aimed to investigate the possible neuroprotective effects of SKP-SCs in 6-OHDA-induced Parkinson's disease (PD) model. Our results showed that the treatment with SKP-SCs prevented SH-SY5Y cells from 6-OHDA-induced apoptosis, accompanied by modulation of apoptosis-related proteins (Bcl-2 and Bax) and the decreased expression of active caspase-3. Furthermore, we confirmed that SKP-SCs might exert protective effects and increase the mitochondrial membrane potential (MMP) through PI3K/AKT/Bcl-2 pathway. Taken together, our results demonstrated that SKP-SCs protect against 6-OHDA-induced cytotoxicity through PI3K/AKT/Bcl-2 pathway in PD model in vitro, which provides a new theoretical basis for the treatment of PD.

Serum omentin-1 and risk of one-year mortality in patients with ischemic stroke.

BACKGROUND: Prior studies suggested that ischemic stroke patients with high omentin-1 concentrations were at a decreased risk of unstable carotid plaque and 3-month poor functional outcome. We aim to evaluate the association between serum omentin-1 and 1-y mortality after ischemic stroke. METHODS: A total of 303 ischemic stroke patients were prospectively followed up at 1 y. Outcome was defined as death occurred during the follow-up period. A multivariable Cox model was used to evaluate the association between serum omentin-1 concentrations and 1-y mortality among ischemic stroke patients. RESULTS: From lowest to highest tertile of serum omentin-1, the 1-y cumulative death rate was 12%, 3.7% and 2.1%, respectively (P = 0.006). The hazard ratio (95% confidence interval) of the highest tertile compared with the lowest tertile was 0.19 (0.04-0.88) for mortality after multivariable adjustment (P for trend < 0.01). The net reclassification index and integrated discrimination improvement were significantly improved in predicting 1-y mortality when omentin-1 data was added to the multivariable Cox regression model. CONCLUSIONS: Among patients with ischemic stroke, high baseline serum omentin-1 was associated with a decreased risk of 1-y mortality. These findings, if confirmed by clinical trials, suggest that increasing omentin-1 concentrations may lower the risk of mortality among ischemic stroke patients.

Clinical potential and current progress of mesenchymal stem cells for Parkinson's disease: a systematic review.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease characterized by severe dyskinesia due to a progressive loss of dopaminergic neurons along the nigro-striatal pathway. The current focus of treatment is to relieve symptoms through administration of levodopa, such as L-3,4-dihydroxy phenylalanine replacement therapy, dopaminergic agonist administration, functional neurosurgery, and gene therapy, rather than preventing dopaminergic neuronal damage. Hence, the application and development of neuroprotective/disease modification strategies is absolutely necessary. Currently, stem cell therapy has been considered for PD treatment. As for the stem cells, mesenchymal stem cells (MSCs) seem to be the most promising. In this review, we analyze the mechanisms of action of MSCs in Parkinson's disease, including growth factor secretion, exocytosis, and attenuation of neuroinflammation. To determine efficacy and protect patients from possible adverse effects, ongoing rigorous and controlled studies of MSC treatment will be critical.

Increased expression of Triad1 is associated with neuronal apoptosis after intracerebral hemorrhage in adult rats.

Objective: It has been demonstrated that Triad1 (2 RING fingers and double RING finger linked 1) negatively regulates myeloid cell growth and induces cell apoptosis. However, its functions in intracerebral hemorrhage (ICH) disease have not been conducted. In this study, the role of Triad1 in rat model of ICH was explored.Methods: We observe an increasing expression of Triad1 in areas adjacent to hematoma after ICH. Immunofluorescence shows that Triad1 is colocalized with neurons, while not microglia or astrocyte, indicates its correlation with neuronal activities following ICH.Results: As neuronal apoptosis is the most crucial event in ICH disease, the expression of active caspase-3 and p53 is also enhanced around the hematoma, which is consistent with Triad1 in expression tendency. In turn, Triad1 depletion in primary cortical neurons decreased the apoptosis of neurons after using Triad1 shRNA.Conclusion: We conclude that inhibition of Triad1 expression might protect the brain from secondary damage following ICH.

Cab45s inhibits neuronal apoptosis following intracerebral hemorrhage in adult rats.

Recent studies have shown that Cab45s, belonging to the CREC family, can fight against apoptosis in the cancer cell lines. Here, we report that Cab45s may involve in neuronal apoptosis at the early stage of intracerebral hemorrhage (ICH) in pathophysiology. We found that expression of Cab45s was enhanced in areas contiguous to hematoma following ICH in adult rats, and that so were the expressions of Glucose-regulated protein 78 (GRP78), pro-apoptotic Bcl-2-associated X protein (Bax) and active caspase-3. In vitro, coimmunoprecipitation analysis indicated the interaction between Cab45s and GRP78. Depletion of Cab45s attenuated the expression of GRP78, but increased the expressions of Bax and caspase-3 in PC12 cells treated with hemin, which finally promoted apoptosis. Together, these results reveal that Cab45s might exert its anti-apoptotic function against neuronal apoptosis. Thus, the study may provide evidences for regulating Cab45s as a potentially reliable treatment for the secondary damage following ICH.

SSTR2 associated with neuronal apoptosis after intracerebral hemorrhage in adult rats.

Objective SSTR2 is a member of superfamily of SST receptor (SSTR), and widely expressed in the brain; however, the knowledge of its functions in area adjacent to hematoma after intracerebral hemorrhage (ICH) is still limited. Method The role of SSTR2 in the processes of ICH was explored by conducting an ICH rat model. Western blot and immunohistochemistry were employed to examine the level of SSTR2 in area adjacent to hematoma after ICH. Immunofluorescent staining was used to observe the spatial correlation of SSTR2 with cellular types adjacent to hematoma after ICH. RNA interference specific to SSTR2 was adopted in PC12 cells to clarify the causal correlation between SSTR2 and neuronal activities. Results Increased expression of SSTR2 was observed and restricted to the neurons adjacent to hematoma following ICH. Immunofluorescent staining showed that SSTR2 was significant increased in neurons, but not astrocytes or microglia. Increasing SSTR2 level was found to be accompanied by the up-regulation of activated caspase-3 and the down-expression of p-Akt in a time-dependent manner. What's more, using SSTR2 RNA interference (SSTR2-RNAi) in PC12 cells, we indicated that SSTR2 might have a pro-apoptotic role in neurons. Conclusion We speculated that SSTR2 might exert its pro-apoptotic function in neurons through inhibiting Akt activity following ICH.

Serum omentin-1 is a novel biomarker for predicting the functional outcome of acute ischemic stroke patients.

BACKGROUND: Recent studies have suggested that omentin-1 plays a critical role in the development of cardiovascular disease. However, reported findings are inconsistent, and no study has evaluated the association between omentin-1 levels and a poor functional outcome after ischemic stroke onset. METHODS: A total of 266 acute ischemic stroke patients were included in this study. All patients were prospectively followed up for 3 months after acute ischemic stroke onset and a poor functional outcome was defined as a major disability or death occurring during the follow-up period. A multivariable logistic model was used to evaluate the association between serum omentin-1 levels and the functional outcome of ischemic stroke patients at 3 months. RESULTS: Ischemic stroke patients with poor functional outcome had significantly lower levels of serum omentin-1 than patients without poor functional outcome at the 3-month follow-up (50.2 [40.2-59.8] vs. 58.3 [44.9-69.6] ng/mL, p<0.01). Subjects in the highest tertile of serum omentin-1 levels had a 0.38-fold risk of having poor functional outcome, compared with those in the lowest tertile (p<0.05). A negative association between omentin-1 levels and poor functional outcome was found (p for trend=0.02). The net reclassification index was significantly improved in predicting poor functional outcome when omentin-1 data was added to the multivariable logistic regression model. CONCLUSIONS: Higher omentin-1 levels at baseline were negatively associated with poor functional outcome among ischemic stroke patients. Omentin-1 may represent a biomarker for predicting poor functional outcome of acute ischemic stroke patients.