Systemic immune-inflammation index upon admission correlates to post-stroke cognitive impairment in patients with acute ischemic stroke.

BACKGROUND: The purpose of this prospective study was to evaluate the association of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), with PSCI in patients with acute ischemic stroke (AIS). METHODS: First-onset AIS patients were consecutively included from January 1, 2022 to March 1, 2023. The baseline information was collected at admission. Fasting blood was drawn the next morning. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCA) 3 months after onset. Logistic regression analysis was performed to explore the correlation between SII, SIRI, and PSCI. Receiver operating characteristic (ROC) was conducted to evaluate the predictive ability of SII. RESULTS: 332 participants were recruited, and 193 developed PSCI. Compared with patients without PSCI, the patients with PSCI had higher SII (587.75 (337.42, 988.95) vs. 345.66 (248.44, 572.89), P<0.001) and SIRI (1.59 (0.95, 2.84) vs. 1.02 (0.63, 1.55), P=0.007). SII and SIRI negatively correlated with MoCA scores (both P<0.05). The multivariable logistic regression analysis indicated that SII was independently associated with PSCI (P<0.001), while SIRI was not. The optimal cutoff for SII to predict PSCI was 676.83×109/L. CONCLUSIONS: A higher level of SII upon admission was independently correlated to PSCI three months later in AIS patients.

High triglyceride-glucose index at admission is a predictor of post-stroke cognitive impairment in patients with acute ischemic stroke.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is a very common complication of ischemic stroke (IS). Triglyceride-glucose (TyG) index was an effective alternative marker of insulin resistance (IR). This prospective study was designed to explore the correlation between TyG index and PSCI. METHODS: Between January 1 2021 to June 30 2022, consecutive patients with first onset IS were enrolled prospectively. Baseline information was collected at admission and fasting blood was drawn the next morning. Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive function at three months after stroke. Multiple regression analysis was used to explore the correlation between PSCI and TyG. Receiver operating characteristic (ROC) was performed to evaluate the predictive ability. RESULTS: Ultimately, 313 patients were enrolled in this study. The TyG index was higher in patients with PSCI than those without PSCI (8.99 (8.55, 9.54) vs. 8.61(8.25, 8.87), P<0.001). The spearman correlation analysis indicated that TyG index was negatively correlated with MoCA score (r=-0.272, P<0.001). The multivariate logistic regression analysis demonstrated that TyG index was correlated with PSCI independently (P<0.001) regardless of whether the patients had diabetes or not. The area under curve (AUC) of the ROC was 0.684 (95%CI=0.635-0.768, P<0.001). The optimal cutoff value of TyG index for predicting PSCI was 8.81, with a sensitivity of 61.7% and a specificity of 73.6%. CONCLUSION: A higher TyG index level at admission was independently correlated with increased risk of PSCI three months later and could be used as a predictor.

Brain diffusion tensor imaging reveals altered connections and networks in epilepsy patients.

Introduction: Accumulating evidence shows that epilepsy is a disease caused by brain network dysfunction. This study explored changes in brain network structure in epilepsy patients based on graph analysis of diffusion tensor imaging data. Methods: The brain structure networks of 42 healthy control individuals and 26 epilepsy patients were constructed. Using graph theory analysis, global and local network topology parameters of the brain structure network were calculated, and changes in global and local characteristics of the brain network in epilepsy patients were quantitatively analyzed. Results: Compared with the healthy control group, the epilepsy patient group showed lower global efficiency, local efficiency, clustering coefficient, and a longer shortest path length. Both healthy control individuals and epilepsy patients showed small-world attributes, with no significant difference between groups. The epilepsy patient group showed lower nodal local efficiency and nodal clustering coefficient in the right olfactory cortex and right rectus and lower nodal degree centrality in the right olfactory cortex and the left paracentral lobular compared with the healthy control group. In addition, the epilepsy patient group showed a smaller fiber number of edges in specific regions of the frontal lobe, temporal lobe, and default mode network, indicating reduced connection strength. Discussion: Epilepsy patients exhibited lower global and local brain network properties as well as reduced white matter fiber connectivity in key brain regions. These findings further support the idea that epilepsy is a brain network disorder.

Prognostic performance of serum YKL-40 for one-year clinical outcomes in acute ischemic stroke.

BACKGROUND: Effects of YKL-40 on one-year clinical outcomes including poor clinical outcome, all-cause mortality, and stroke recurrence among acute ischemic stroke (AIS) patients remained elusive. The purpose of this study was to explore the association between serum YKL-40 at admission and one-year clinical outcomes in AIS patients. METHODS: In this prospective cohort study, a total of 1002 participants out of 1361 AIS patients from two centers were included for current analysis. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. Multivariable logistic or Cox regression were performed to explore the independent association of YKL-40 with one-year clinical outcomes, including poor outcome (modified Rankin Scale of 3-6), all-cause mortality, and recurrent stroke. C-statistic, net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the discriminatory and predictive power of YKL-40 when added to conventional model. RESULTS: Compared with the first quartile of YKL-40, the adjusted odds ratios or hazard ratios with 95% confidence intervals of the fourth quartile were 3.032 (1.627-5.650) for poor outcome, 2.886 (1.320-6.308) for all-cause mortality and 1.694 (0.906-3.169) for recurrent stroke. The addition of serum YKL-40 to conventional model significantly improved reclassification for poor outcome (NRI 0.053, P = 0.031; IDI 0.018, P = 0.001) and all-cause mortality (NRI 0.162, P = 0.036). CONCLUSIONS: Elevated serum YKL-40 at admission might be independently associated with one-year poor outcome and all-cause mortality but not stroke recurrence among Chinese AIS patients.

Correlation Between Cognitive Impairment and Homocysteine and S100B Protein in Patients with Progressive Ischemic Stroke.

Purpose: This study aimed to investigate the relationship between cognitive impairment and homocysteine (Hcy) and S100B protein in patients with progressive ischemic stroke (PIS). Patients and Methods: A total of 158 patients with PIS hospitalized in the Department of Neurology in Taixing People's Hospital from January 2020 to March 2022 were enrolled in the study. After 90 days of follow-up, the patients were divided into two groups according to the MoCA score-99 cases with cognitive impairment group (observation group) and 59 cases with cognitive normal group (control group). Causal diagram was drawn to assess the association between risk factors and PIS with observation group. The risk factors indicators of cognitive impairment in patients with PIS were screened. The related predictive indicators were screened by multivariate logistic regression analysis, and Pearson correlation analysis. The predictive value was analyzed by Receiver Operating Characteristic (ROC) curve. Results: Multivariate logistic regression analysis showed that age, hypertension, lesion position, Hcy and S100B protein were related risk factors for cognitive impairment in patients with PIS. Pearson correlation analysis was conducted between Hcy and S100 B protein and MoCA score, and revealed that Hcy and S100 B protein were negatively correlated with MoCA score. ROC curve analysis showed that the Area Under the Curve (AUC) of S100 B protein and Hcy in identifying cognitive impairment after PIS was 0.709 and 0.673, respectively, and the combined AUC of Hcy and S100B protein in predicting cognitive impairment after PIS was 0.739. Conclusion: Hcy and S100B protein are related risk factors for cognitive impairment in patients with PIS, and may be used as in a prediction model to predict cognitive impairment after PIS in the future.

Effect of cognitive behavioral intervention on anxiety, depression, and quality of life in patients with epilepsy.

OBJECTIVE: This study aimed to investigate the effect of cognitive behavioral therapy (CBT) on quality of life, anxiety, and depression in patients with epilepsy. METHODS: Each study subject was randomly assigned to a CBT (n=46) or control (n=49) group (1:1 ratio), and the first group underwent an 8-week CBT treatment. Anxiety, depression, and quality of life (QOLIE-31) were assessed at both baseline and endpoint using the Self-Rating Anxiety Scale (SAS), Hamilton Depression Scale (HDMA) and quality of life in Epilepsy-31 (QOLIE-31) scales. The statistical analyses included between-and within-group comparisons of the effects of CBT on these measures and associations with demographic and clinical variables. RESULTS: No differences were found between variables at baseline (P>0.05). The repeated-measures analyses found that CBT group had greater improvement in depression score compared to the control group (P<0.05). The analysis of anxiety score showed that compared to the control group, CBT intervention had no statistical significance in the total anxiety population. However, the CBT intervention decreased anxiety in women and Combined-drug group (P<0.05). The CBT group had greater improvement in overall score, medication effect, and seizure worry score than the control group (P<0.05). Stratified analysis found total and medication effects score of CBT intervention group for the combined-drug group were higher than those of the single drug group (P<0.05). CONCLUSION: Increases in overall scores, seizure worry, cognitive functioning, and medication effect were better in the CBT group. CBT can improve anxiety, depression, and quality of life in patients with epilepsy. Women and combined-drug patients with epilepsy benefit most from CBT.

miR-383-5p Regulated by the Transcription Factor CTCF Affects Neuronal Impairment in Cerebral Ischemia by Mediating Deacetylase HDAC9 Activity.

Stroke, the leading cause of long-term disability worldwide, is caused by the blockage or hemorage of cerebral arteries. The resultant cerebral ischemia causes local neuronal death and brain injury. Histone deacetylase 9 (HDAC9) has been reported to be elevated in ischemic brain injury, but its mechanism in stroke is still enigmatic. The present study aimed to unveil the manner of regulation of HDAC9 expression and the effect of HDAC9 activation on neuronal function in cerebral ischemia. MicroRNAs (miRNAs) targeting HDAC9 were predicted utilizing bioinformatics analysis. We then constructed the oxygen glucose deprivation (OGD) cell model and the middle cerebral artery occlusion (MCAO) rat model, and elucidated the expression of CCCTC binding factor (CTCF)/miR-383-5p/HDAC9. Targeting between miR-383-5p and HDAC9 was verified by dual-luciferase reporter assay and RNAi. After conducting an overexpression/knockdown assay, we assessed neuronal impairment and brain injury. We found that CTCF inhibited miR-383-5p expression via its enrichment in the promoter region of miR-383-5p, whereas the miR-383-5p targeted and inhibited HDAC9 expression. In the OGD model and the MCAO model, we confirmed that elevation of HDAC9 regulated by the CTCF/miR-383-5p/HDAC9 pathway mediated apoptosis induced by endoplasmic reticulum stress, while reduction of HDAC9 alleviated apoptosis and the symptoms of cerebral infarction in MCAO rats. Thus, the CTCF/miR-383-5p/HDAC9 pathway may present a target for drug development against ischemic brain injury.

Electroacupuncture Promotes Autophagy by Regulating the AKT/mTOR Signaling Pathway in Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is a complex neurological disease, and its occurrence and development are closely related to the autophagy signaling pathway. However, the mechanism by which electroacupuncture (EA) affects the regulation of autophagy has not been fully elucidated. TLE gene chip dataset GSE27166 and data from rats without epilepsy (n = 6) and rats with epilepsy (n = 6) were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) in the TLE and control groups were identified with the online tool GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to analyse the functional and pathway enrichment of genes in the most important modules. A rat model of TLE induced by lithium-pilocarpine treatment was established. EA treatment at DU20 and DU14 in TLE rats was performed for 2 weeks. Neuronal regeneration was determined using immunofluorescence staining. The protein levels of AKT/mTOR signaling pathway and autophagy markers were detected through western blotting and immunohistochemistry. This study identified 1837 DEGs, including 798 upregulated genes and 1039 downregulated genes. GO enrichment and KEGG analyses were performed on DEGs and revealed functional enrichment mainly in the mTOR signaling pathway and autophagy-animal. Furthermore, the number of mature neurons was significantly increased upon coexpressing BrdU/NeuN in TLE rats treated with EA. Western blotting and immunohistochemistry results showed significantly decreased levels of the phosphorylated-AKT and p-mTOR in the hippocampal CA3 and DG regions of TLE rats with EA treatment. And increased p-ULK1/ULK1, LC3-II/LC3-I and p62 levels in TLE rats with EA stimulation. Therefore, this study suggested that EA promoted autophagy in hippocampal neurons during the onset of epilepsy by regulating the AKT/mTOR signaling pathway to treat epilepsy.

Level of LncRNA GAS5 and Hippocampal Volume are Associated with the Progression of Alzheimer's Disease.

Purpose: We evaluated the diagnostic value of long non-coding RNA growth arrest-specific transcript 5 (GAS5) and its relationship with hippocampal volume in Alzheimer's disease (AD). Patients and Methods: One hundred and eight patients with AD and 83 healthy controls were included, and demographic data, biochemical parameters, GAS5 levels, and hippocampal volume were recorded. Chi-squared tests or independent sample t-tests were used to compare the baseline characteristics, relative expression of GAS5, and hippocampal volume. Correlations between variables were determined using Spearman's rank correlation test. Receiver operating characteristic (ROC) curves were generated to compare the diagnostic value of GAS5 and total hippocampal volume in AD. Results: The levels of GAS5 were significantly upregulated in patients with AD compared with those in controls and were negatively correlated with MMSE score. There were differences in left hippocampal volume, right hippocampal volume, and total hippocampal volume between the two groups. Total hippocampal volume was positively correlated with MMSE score and negatively correlated with GAS5 expression in patients with AD. The area under the curve (AUC) of for GAS5 expression was 0.831, the sensitivity was 61.1%, and the specificity was 95.2%. The AUC of the combined total hippocampal volume was 0.891, the sensitivity was 74.1%, and the specificity was 92.8%. Conclusion: The results suggested that GAS5 may be an excellent indicator of AD progression alone or in combination with hippocampal volume.

Procalcitonin related to stroke-associated pneumonia and clinical outcomes of acute ischemic stroke after IV rt-PA treatment.

To investigate the possible relationship between procalcitonin (PCT) and stroke-associated pneumonia (SAP) as well as clinical outcomes after recombinant tissue plasminogen activator (rt-PA) treatment of AIS. From June 2015 to December 2019, 173 consecutive patients with AIS after IV rt-PA treatment were prospectively enrolled. Serum PCT concentrations were measured after admission. Multivariate logistic regression analysis was used to examine the potential risk factors of SAP, poor outcome and mortality. Of the 173 patients, 49 (28.3%) participants were identified with SAP, 87 (50.3%) with poor outcome, and 28 (16.2%) with mortality. Multivariate logistic regression analysis demonstrated that patients with PCT in the second [odds ratio (OR) 4.413; 95% confidence interval (CI) 1.331-14.634; P = 0.015] and third tertile (OR 10.958; 95% CI 3.524-34.071; P < 0.001) were more likely to have SAP compared with the first tertile. Besides, PCT was an independent predictor of 3-month poor outcome (OR 3.219, 95% CI 1.291-8.028, P = 0.007) and mortality (OR 7.538, 95% CI 2.061-27.564, P = 0.002). In receiver operating characteristic (ROC) curve analysis, the diagnostic and prognostic accuracy of PCT was higher than hs-CRP. This study demonstrated that PCT was a reliable diagnostic and prognostic biomarker of SAP and poor clinical outcomes in Chinese AIS patients after IV rt-PA treatment.

The Relationship Between Serum YKL-40 Levels on Admission and Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke.

BACKGROUND: Stroke-associated pneumonia (SAP) is a standout complication after acute ischemic stroke (AIS), with a prevalence of 7-38%. The aim of this prospective study was to investigate the relationship between serum YKL-40 levels at admission and SAP. METHODS: Between August 2020 and February 2021, consecutive AIS patients from two centers were enrolled prospectively. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. We performed logistic regression analyses to explore the relationship between YKL-40 and SAP. Receiver operating characteristic curve was also used to assess the predictive ability of YKL-40 in predicting SAP. RESULTS: Ultimately, a total of 511 AIS patients were recruited. Multivariate logistic regression analysis showed that YKL-40 was independently related to SAP, whether as a continuous variable or as quartiles (P=0.001). The area under curve of YKL-40 to predict SAP was 0.765. The optimal cutoff value of YKL-40 as a predictor of SAP was determined to be 206.4 ng/mL, where the sensitivity was 63.1% and the specificity was 82.0%. CONCLUSION: Our study demonstrated that YKL-40 might be considered as a useful biomarker to predict SAP in AIS patients.

Pridopidine for the Improvement of Motor Function in Patients With Huntington's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Huntington's disease (HD) is a progressive neurodegenerative disorder. Generally, it is characterized by deficits in cognition, behavior, and movement. Recent studies have shown that pridopidine is a potential and effective drug candidate for the treatment of HD. In the present study, we performed a meta-analysis to evaluate the efficacy and safety of pridopidine in HD. Methods: The MEDLINE, EMBASE, CENTRAL, and Clinicaltrials.gov databases were searched for randomized controlled trials (RCTs) which had that evaluated pridopidine therapy in HD patients. Results: We pooled data from 1,119 patients across four RCTs. Patients in the pridopidine group had a significantly lower Unified Huntington's Disease Rating Scale (UHDRS)-modified Motor Score (mMS) (MD -0.79, 95% CI = -1.46 to -0.11, p = 0.02) than those in the placebo group. Additionally, no differences were observed in the UHDRS-Total Motor Score (TMS) (MD -0.91. 95% CI = -2.03 to 0.21, p = 0.11) or adverse events (RR 1.06, 95% CI = 0.96 to 1.16, p = 0.24) in the pridopidine and placebo groups. In the subgroup analysis, the short-term (≤12 weeks) and long-term (>12 weeks) subgroups exhibited similar efficacy and safety with no statistical significance in TMS, mMS, or adverse events. However, TMS (MD -1.50, 95% CI = -2.87 to -0.12, p = 0.03) and mMS (MD -1.03, 95% CI = -1.87 to -0.19, p = 0.02) were observed to be improved significantly when the dosage of pridopidine ≥90 mg/day. Additionally, pridopidine (≥90 mg/day) increased total adverse events (RR 1.11, 95% CI = 1.00 to 1.22, p = 0.04) compared with placebo. On this basis, we analyzed the incidence of various adverse events when the dosage was ≥90 mg/day. Nonetheless, these results were within the acceptable threshold, although patients developed symptoms, such as nasopharyngitis and insomnia. Conclusion: Pridopidine improved mMS and had no statistical significance in association with TMS or adverse events. Pridopidine (≥90 mg/day) improved TMS and mMS but increased adverse events, such as nasopharyngitis and insomnia. More RCTs were expected to assess pridopidine in HD.

Long noncoding RNA Nespas inhibits apoptosis of epileptiform hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway.

Epilepsy is one of the most common neurological diseases with spontaneous recurrent seizures. Long noncoding RNAs (lncRNAs) are crucial modulators in numerous diseases, including epilepsy. However, the functional role and potential mechanism of lncRNA Nespas in epilepsy remain unknown. Our study clarified that Nespas was underexpressed in epileptiform hippocampal tissues and neurons. Furthermore, Nespas promoted hippocampal neuron viability and proliferation, and inhibited hippocampal neuron apoptosis. Mechanistically, Nespas interacted with microRNA 615-3p (miR-615-3p) in epileptiform hippocampal neurons. 26S proteasome non-ATPase regulatory subunit 11 (Psmd11) was a downstream target of miR-615-3p, and Nespas elevated Psmd11 expression via competitively binding to miR-615-3p in epileptiform hippocampal neurons. In addition, rescue assays suggested that Nespas promoted hippocampal neuron viability and proliferation, and suppressed hippocampal neuron apoptosis by upregulation of Psmd11. Furthermore, Nespas suppressed the PI3K/Akt/mTOR pathway via upregulating Psmd11 in epileptiform hippocampal neurons. This report explored the function and regulatory mechanism of Nespas in epileptiform hippocampal neurons for the first time. Our findings revealed that Nespas suppressed the apoptosis of epileptiform hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway via upregulation of Psmd11 at a miR-615-3p dependent way, indicating that Nespas may offer a new direction for the treatment of epilepsy.

Identification of Parkinson's disease-related pathways and potential risk factors.

OBJECTIVE: To identify Parkinson's disease (PD)-associated deregulated pathways and genes, to further elucidate the pathogenesis of PD. METHODS: Dataset GSE100054 was downloaded from the Gene Expression Omnibus, and differentially expressed genes (DEGs) in PD samples were identified. Functional enrichment analyses were conducted for the DEGs. The top 10 hub genes in the protein-protein interaction (PPI) network were screened out and used to construct a support vector machine (SVM) model. The expression of the top 10 genes was then validated in another dataset, GSE46129, and a clinical patient cohort. RESULTS: A total of 333 DEGs were identified. The DEGs were clustered into two gene sets that were significantly enriched in 12 pathways, of which 8 were significantly deregulated in PD, including cytokine-cytokine receptor interaction, gap junction, and actin cytoskeleton regulation. The signature of the top 10 hub genes in the PPI network was used to construct the SVM model, which had high performance for predicting PD. Of the 10 genes, GP1BA, GP6, ITGB5, and P2RY12 were independent risk factors of PD. CONCLUSION: Genes such as GP1BA, GP6, P2RY12, and ITGB5 play critical roles in PD pathology through pathways including cytokine-cytokine receptor interaction, gap junctions, and actin cytoskeleton regulation.

Long-noncoding RNA Peg13 alleviates epilepsy progression in mice via the miR-490-3p/Psmd11 axis to inactivate the Wnt/ß-catenin pathway.

Epilepsy, one of the most common neurological diseases with spontaneous recurrent seizures, is a severe health problem globally. The present study aimed to study the role and upstream mechanism of 26S proteasome non-ATPase regulatory subunit 11 (Psmd11) in epilepsy. In the current paper, epileptic mice models were successfully established. Hematoxylin and eosin (HE) staining was performed to reveal morphology of hippocampal tissues. Nissl's staining was performed for detection of neuron injury. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect concentrations of pro-inflammatory cytokines. The expression of Psmd11 was downregulated in the hippocampal tissues of epileptic mice, and overexpression of Psmd11 improved the spatial learning and memory of epileptic mice. Further, upregulation of Psmd11 protected epileptic hippocampal neurons from injury. Moreover, Psmd11 overexpression inhibited cell apoptosis, suppressed the activities of microglia and astrocytes, as well as reduced inflammatory response in epileptic hippocampi. Psmd11 was a downstream target of miR-490-3p. Long noncoding RNA (lncRNA) Peg13 bound with miR-490-3p to upregulate Psmd11. Subsequently, rescue experiments revealed that Peg13 suppressed the progression of epilepsy via upregulating Psmd11. Furthermore, Psmd11 was verified to inactivate the Wnt/ß-catenin pathway. Peg13 repressed the Wnt/ß-catenin pathway via upregulation of Peg13. In conclusion, this paper illuminated the function and upstream mechanism of Psmd11 in epilepsy. Psmd11 was upregulated by Peg13 at a miR-490-3p dependent way, thus inactivating the Wnt/ß-catenin pathway and alleviating epilepsy course in mice, which may be a promising approach for epilepsy treatment.

Efficacy of remote limb ischemic conditioning on poststroke cognitive impairment.

The impact of remote limb ischemic conditioning on poststroke cognitive impairment was evaluated with 104 first-time patients of noncardiac ischemic stroke. During the acute phase the patients were randomized into control and remote limb ischemic conditioning groups. Both groups received standard treatment, while the remote limb ischemic conditioning group received additional remote limb ischemic conditioning treatment for 6 months. All participants underwent neuropsychological evaluation, transcranial Doppler detection, P300 event-related potential and brachial-ankle pulse wave velocity measurements, and determination of serum intercellular adhesion molecule-1 and endothelin-1 levels both at admission and 6 months poststroke. The number of cases with poststroke cognitive impairment in each group was evaluated 6 months poststroke. No statistically significant difference was found in demographic data or baseline detection indices at admission between the two groups. However, at 6 months poststroke, the remote limb ischemic conditioning group had significantly higher total Montreal Cognitive Assessment score and its domains of visuospatial and executive functioning and attention scores, significantly lower activity of daily living scale score, shorter P300 latency, and higher amplitude compared with the control group. Moreover, the middle cerebral artery, average blood flow velocity was significantly higher, while the middle cerebral artery-pulsation index, basilar artery pulsation index, and the levels of brachial-ankle pulse wave velocity, intercellular adhesion molecule-1, and endothelin-1 were significantly lower in the remote limb ischemic conditioning group compared with the control group. These results demonstrate that remote limb ischemic conditioning causes a significant improvement in cognitive domains, such as visuospatial and executive functioning and attention, and is therefore linked with reduced incidence of poststroke cognitive impairment.

Serum lipoprotein-associated phospholipase A2 predicts the formation of carotid artery plaque and its vulnerability in anterior circulation cerebral infarction.

OBJECTIVE: Circulation inflammation markers such as high-sensitive C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are considered as predictors of cerebral and cardiac vascular diseases. However, the role of hsCRP and Lp-PLA2 in the anterior circulation cerebral infarction (ACI) is to be elaborated. PATIENTS AND METHODS: We included 100 patients with acute anterior circulation cerebral infarction (AaCI group) and 50 non-infarction subjects (control group). Carotid artery was detected by color Doppler ultrasound. Subjects were grouped based on carotid intima-media thickness (IMT) and degree of stability of carotid atherosclerotic plaque. The levels of hsCRP and Lp-PLA2 were measured in corresponding groups and the association was analyzed. RESULTS: hsCRP and Lp-PLA2 levels were the risk factors for AaCI. With the increment of carotid IMT and degree of plaque instability, the level of hsCRP and Lp-PLA2 showed an elevating tendency. hsCRP and Lp-PLA2 levels were significantly higher in plaque formation group than in IMT normal group (P=0.002 and P=0.001, respectively). hsCRP and Lp-PLA2 levels were significantly higher in vulnerable plaque group than in mixed plaque group and stable plaque group (P=0.003, P<0.001 for hsCRP and P<0.001, P<0.001 for Lp-PLA2). Lp-PLA2 was finally included in the atherosclerotic plaque model (OR=1.019, 95% confidence interval (CI): 1.003-1.035, P=0.020) and vulnerable plaque model (OR=1.041, 95%CI: 1.017-1.065, P=0.001) by performing multivariate logistic regression analysis. The area under the ROC curve (AUC) of Lp-PLA2 levels for atherosclerotic plaque was 0.746 (95% CI: 0.628-0.865, P<0.001). The optimal cut-off value for Lp-PLA2 level was 267.5ng/ml, and its sensitivity and specificity for diagnosis of atherosclerotic plaque were 70.8% and 67.1%, respectively. CONCLUSIONS: The current study demonstrates that hsCRP and Lp-PLA2 are among the risk factors for AaCI. Elevated hsCRP and Lp-PLA2 are associated with carotid plaque formation. Univariate and multivariate logistic regression analysis suggests that elevated Lp-PLA2 is the independent risk factor for carotid plaque and its vulnerability.

The E3 ubiquitin ligase seven in absentia homolog 1 may be a potential new therapeutic target for Parkinson's disease.

In this study, we investigated the effect of an antibody against E3 ubiquitin ligase seven in absentia homolog 1 (SIAH-1) in PC12 cells. 1-Methyl-4-phenylpyridinium (MPP(+)) treatment increased α-synuclein, E1 and SIAH-1 protein levels in PC12 cells, and it reduced cell viability; however, there was no significant change in light chain 3 expression. Treatment with an SIAH-1 antibody decreased mRNA expression levels of α-synuclein, light chain 3 and SIAH-1, but increased E1 mRNA expression. It also increased cell viability. Combined treatment with MPP(+) and rapamycin reduced SIAH-1 and α-synuclein levels. Treatment with SIAH-1 antibody alone diminished α-synuclein immunoreactivity in PC12 cells, and reduced the colocalization of α-synuclein and light chain 3. These findings suggest that the SIAH-1 antibody reduces the monoubiquitination and aggregation of α-synuclein, promoting its degradation by the ubiquitin-proteasome pathway. Consequently, SIAH-1 may be a potential new therapeutic target for Parkinson's disease.

Proxies of cognitive reserve and their effects on neuropsychological performance in patients with mild cognitive impairment.

Cognitive reserve (CR) modulates the relationship between clinical and pathological phenotypes by restricting the negative effect of cerebral lesions on cognition, according to the CR hypothesis. In this study, we evaluated 18 healthy subjects and 21 patients with mild cognitive impairment (MCI) using conventional MRI, magnetic resonance spectroscopy (MRS), the Mini-Mental State Examination (MMSE), the Wechsler Memory Scale (WMS), and the Montreal Cognitive Assessment (MoCA). The MMSE, WMS and MoCA assessments were repeated 1year later. The MRS analysis results showed that the N-acetyl-aspartate peak area (NAA; t=5.122, P<0.001) and the NAA/creatine (Cr), NAA/myo-inositol (mI) and NAA/choline (Cho) ratios were significantly changed in patients with MCI compared with the control subjects (all P<0.01). The MoCA was significantly related to the NAA/Cho ratio (R=0.443), the NAA/Cr ratio (R=0.533), and the NAA peak area (R=0.814; all P<0.05), but was unrelated to the NAA/mI ratio (R=0.400, P=0.072). We found that the hippocampal volume was significantly correlated with the MoCA, WMS and MMSE (R=0.704, 0.677, 0.542 respectively; all P<0.05). Education level had a positive effect on changes in the MoCA, MMSE, and WMS 1year later. We believe that MoCA and WMS results, MRI hippocampal volume and other related indicators (NAA peak area, NAA/Cr ratio, NAA/mI ratio, and NAA/Cho ratio) may reflect the degree of CR capacity, and that the number of years of education can significantly affect the changes in cognitive function in patients with MCI. Therefore, increasing levels of education and life skills training can help increase CR, reduce the risk of MCI, and slow down the appearance of clinical manifestations and clinical progress in patients with MCI.

Elevated plasma endothelial microparticles in Alzheimer's disease.

BACKGROUND/AIMS: Endothelial microparticles (EMPs) in plasma are elevated in several vascular diseases. Alzheimer's disease (AD) is associated with microcirculatory injury, capillary blocking and disruption of the blood-brain barrier. We wanted to test the hypothesis that EMPs would be increased in AD patients and would correlate with a cognitive decline, and to determine if EMPs are released as a result of activation or apoptosis/necrosis in AD. METHODS: EMP levels in plasma of AD patients and controls were quantified by flow cytometry. EMP markers for apoptosis/necrosis [platelet/endothelial cell adhesion molecule-1 (PECAM-1)/CD31] and for activation (E-selectin/CD62e) were evaluated. The EMP CD62E/CD31 populations ratio of ≤1.0 was used to differentiate activation from apoptosis. RESULTS: Significantly higher CD31+/CD42- and CD62e+/CD42- counts were observed in the AD group relative to the controls (p < 0.05). There was no difference between the moderate- to-severe AD group and the mild AD group. Significant correlations were found between circulating EMP counts and Mini-Mental State Examination and AD Assessment cognition (ADAS-cog) score. Multivariate regression analysis demonstrated the persistence of significant correlations between ADAS-cog score and CD31+/CD42- EMPs. CONCLUSION: The (PECAM-1)/CD31 ratio demonstrated that EMPs were generated via apoptosis/necrosis and not by activation. Certain circulating EMP phenotypes may be associated with a cognitive decline of AD patients. EMP analysis shows a promising contribution to understanding vascular pathophysiology in AD.