Multicenter registry study of cerebral venous thrombosis in china (RETAIN-CH): Rationale and design.

BACKGROUND AND RATIONALE: Cerebral venous thrombosis (CVT) is a rare cerebrovascular disorder that mainly affects young and middle-aged adults. Epidemiological data on the incidence, risk factors, diagnosis, treatment, and prognosis of CVT are lacking in China. In addition, there is a lack of evidence from large, multicenter, real-world studies on the efficacy and safety of endovascular. AIM: To understand the incidence, diagnosis and treatment status of CVT in China and to estimate the effectiveness and safety of endovascular treatment in the real-world. METHODS: A multicenter, retrospective observational cohort study will be conducted on CVT patient records from 104 hospitals, between January 1, 2018 and June 30, 2022, identified using a 2-stage cluster sampling design based on per capita gross domestic product. Each enrolled participant is required to complete a further follow-up, which includes the current situation and the assessment at 3 and 12 months after discharge. STUDY OUTCOMES: The outcomes of this study will include the current status of the incidence, pathogenesis, etiology, clinical symptoms, diagnosis, and treatment of CVT in China, as well as the effectiveness and safety of endovascular treatment in the real-world. DISCUSSION: Results from this study will provide evidence on the incidence, specific risk factors, symptomatic and imaging features, and clinical outcomes of CVT in China as well as indicate whether endovascular treatment is superior to medical management alone for patients with acute CVT in the real-world. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov. IDENTIFIER: NCT05448248.

Prevalence of stroke in China, 2013-2019: A population-based study.

Background: The stroke burden in China has increased during the past 40 years. The present study aimed to determine the recent trends in the prevalence of stroke from 2013 to 2019 stratified by sociodemographic characteristics, including sex, age, residence, ethnicity, and province within a population-based screening project in China. Methods: We made use of data generated from 2013 to 2019 in the China Stroke High-risk Population Screening Program. All living subjects with confirmed stroke at interview were considered to have prevalent stroke. All analyses of prevalence of stroke were weighted and results were presented as percentage and 95% confidence interval (CI). Findings: A total of 4229,616 Chinese adults aged ≥40 years from 227 cities in the 31 provinces were finally included. The enrollment rate ranged from 58.8% (2017) to 67.8% (2013). The weighted prevalence of stroke increased annually from 2013 to 2019, being 2.28% (95% CI: 2.28-2.28%) in 2013, 2.34% (2.34-2.35%) in 2014, 2.43% (2.43-2.43%) in 2015, 2.48% (2.48-2.48%) in 2016, 2.52% (2.52-2.52%) in 2017, 2.55% (2.55-2.55%) in 2018, and 2.58% (2.58-2.58%) in 2019 (p for trend <0.001). The weighted prevalence of stroke was higher for male sex, older age, and residence in rural and northeast areas. Interpretation: The prevalence of stroke in China and most provinces has continued to increase in the past 7 years (2013-2019). These findings, especially in provinces with high stroke prevalence, can help public health officials to increase province capacity for stroke and related risk factors prevention. Fundings: This study was supported by grants from the National Major Public Health Service Projects.

Monocytohigh-density lipoprotein ratio has a high predictive value for the diagnosis of multiple system atrophy and the differentiation from Parkinson's disease.

Background and purpose: Inflammation is closely related to the pathogenesis of multiple system atrophy (MSA). As markers of inflammation, the monocyte to high-density lipoprotein ratio (MHR), neutrophil to lymphocyte ratio (NLR), and red cell distribution width to platelet ratio (RPR) have been proven to be associated with a large variety of diseases. The aim of this study was to explore the association between inflammatory markers (MHR, NLR, and RPR) and MSA, and the difference between MSA and Parkinson's disease (PD) was further compared by these inflammatory markers. Materials and methods: This study was divided into three groups: 47 patients with MSA, 125 patients with PD, and 124 healthy controls. The corresponding laboratory indicators of subjects were collected and analyzed to obtain MHR, NLR, and RPR values. Results: Compared with healthy controls, the MHR, NLR, and RPR were higher in the MSA group (P < 0.05), and the MHR was higher in the MSA group than in the PD group (P < 0.001). Multivariate logistic regression analysis showed that MHR*10 (corrected OR = 1.312, 95% CI 1.093-1.575) and RPR*100 (corrected OR = 1.262, 95% CI 1.055-1.509) were positively correlated with the risk of MSA. The receiver operating characteristic (ROC) curve indicated that the areas under the curve (AUCs) of the MHR, NLR, and RPR for predicting MSA were 0.651 (95% CI 0.562-0.74; P < 0.05), 0.6 (95% CI 0.501-0.699; P < 0.05), and 0.612 (95% CI 0.516-0.708; P < 0.05), respectively. The AUC of MSA and PD predicted by the MHR was 0.727 (P < 0.001). When the cut-off value was 0.38, the sensitivity and specificity were 60 and 77%, respectively. Spearman correlation analysis showed that the MHR was significantly and positively correlated with the course of MSA cerebellar type (MSA-C) patients. Conclusion: There may be peripheral inflammation in patients with MSA. Compared with NLR and RPR, MHR has higher predictive value for the diagnosis and differential diagnosis of MSA.

Polydatin Prevents Neuroinflammation and Relieves Depression via Regulating Sirt1/HMGB1/NF-κB Signaling in Mice.

Depression is a prevalent psychiatric disorder with a significant health impact and economic burden worldwide. Unfortunately, the exact pathogenesis of depression is not well understood. Neuroinflammation and microglial activation play an essential role in the pathogenesis of depression. Previous studies have shown that polydatin has anti-inflammatory and antioxidant properties. However, the link between polydatin and depression remains unclear. Therefore, the objective of this study was to investigate the antidepressant effect of polydatin in lipopolysaccharide (LPS)-induced depression in mice and its possible mechanism. Adult male C57BL/6 J mice were used in this study. The polydatin and LPS were injected intraperitoneally daily for 5 days. In addition, the EX527, an inhibitor of Sirt1, was injected intraperitoneally daily and 1 h before the polydatin injection. The behavior tests were performed to elucidate the depression-like behaviors. The Sirt1/HMGB1/NF-κB pathway expression was detected by western blot, ELISA, and immunofluorescence staining. Polydatin can significantly improve LPS-induced depression-like behavior in mice. Treatment with polydatin increased the expression of the Sirt1 but decreased the expression of the HMGB1, p-NF-κB, IL-1b, and TNF-α in the LPS-induced depression mice. In addition, the EX527 abolished the anti-depressive effects of the polydatin and the levels of Sirt1 protein. These findings suggested that the polydatin reversed the depressive effects through the Sirt1/HMGB1/NF-κB signaling in the LPS-induced depression mice. Therefore, polydatin can be used in the treatment of depression.

Oridonin relieves depressive-like behaviors by inhibiting neuroinflammation and autophagy impairment in rats subjected to chronic unpredictable mild stress.

Major depressive disorder (MDD) is a severe life-threatening disorder with increasing prevalence. However, the mechanistic interplay between depression, neuroinflammation, and autophagy is yet to be demonstrated. This study investigated the effect of Oridonin on CUMS-induced depression, neuroinflammation, and autophagy impairment. Male 4-week-old Sprague-Dawley rats were subjected to chronic unpredictable mild stress (CUMS), some of which were injected with Oridonin, fluoxetine (FLX), or their combination at different durations of CUMS. CUMS significantly increased the levels of cytokines (IL-1ß, IL-18, and caspase-1), reduced autophagy-related protein levels (Beclin-1, p62, Atg5, and LC3B), and caused microglia cells activation. Oridonin prevented and reversed the depressive-like behavior. Furthermore, it has a stronger and longer-lasting antidepressant effect than FLX. And the antidepressant effect of Oridonin in combination with fluoxetine was greater than that of high-dose fluoxetine alone. In addition, Oridonin significantly normalized autophagy-related protein levels, and reduced levels of cytokines by blocking the interaction between NLRP3 and NEK7. Similarly, Oridonin abolished levels of cytokines and reversed autophagy impairment in LPS-activated BV2 cells. All these results supported our hypothesis that Oridonin possesses potent anti-depressive action, which might be mediated via inhibition of neuroinflammation and autophagy impairment by blocking the interaction between NLRP3 and NEK7.

Tert-butylhydroquinone prevents neuroinflammation and relieves depression via regulation of NLRP3 signaling in mice.

Depression is a common psychiatric disorder, which seriously affects people's health and quality of life. Current treatments, which mainly focus on neurotransmitter levels, are not effective in many patients. Recent studies have shown that neuroinflammation has certain correlation with the pathogenesis of depression. Tert-butylhydroquinone (TBHQ) is an antioxidant with an anti-inflammatory effect. The present study evaluated the effects of TBHQ on the improvement of depression-like behaviors induced by lipopolysaccharide (LPS) in mice and its possible mechanism. Behavioral test results showed that TBHQ treatment could significantly improve the depression-like behaviors of mice. Western blot results showed that TBHQ treatment inhibited the protein expression of NLRP3, Caspase-1, IL-1ß, and IL-18, which induced by LPS. Immunofluorescence staining results showed that TBHQ treatment inhibited the activation of microglia induced by LPS. These results suggested that, by inhibiting LPS-induced neuroinflammation and microglia activation, TBHQ could effectively improve LPS-induced inflammation-related depression-like behavior through modulating the NLRP3 signaling pathway.

Higher serum occludin after successful reperfusion Is associated with early neurological deterioration.

AIMS: Early neurological deterioration (END) is an important factor that affects prognosis in patients with acute ischemic stroke. We explored the relationship between serum occludin levels after successful reperfusion and END in patients treated with endovascular thrombectomy (EVT). METHODS: We prospectively enrolled 120 stroke patients who underwent EVT with successful reperfusion. Enzyme-linked immunosorbent assay was used to detect the serum occludin levels on admission and within 1 h after successful reperfusion. Receiver operating characteristic curves (ROC) and regression analysis were used to compare the relationship between serum occludin and END after thrombectomy. RESULTS: Among the 120 patients, 36 (30%) experienced END. The END group had higher serum occludin levels than the non-END group after successful reperfusion [4.31 (3.71-5.38) vs 6.32 (5.88-6.99), p < 0.001]. The ROC curve showed that postoperative serum occludin levels had a significant prediction value for END (AUC: 0.86, p < 0.001). Regression analysis showed that serum occludin was an independent risk factor for END in EVT patients (adjusted odds ratio: 4.46, 95% confidence interval: 1.92-10.32; p < 0.001). CONCLUSIONS: The higher serum occludin levels were strongly related to END after successful reperfusion. Serum occludin may be an independent risk factor for END in EVT patients.

RGFP966 is protective against lipopolysaccharide-induced depressive-like behaviors in mice by inhibiting neuroinflammation and microglial activation.

Depression is a prevalent mental disorder. However, its pathophysiological mechanism has still remained elusive, and a limited number of effective treatments have been presented. Recent studies have shown that neuroinflammation and microglial activation are involved in the pathogenesis of depression. Histone deacetylase 3 (HDAC3) has neurotoxic effects on several neuropathological conditions. The inhibition of HDAC3 has been reported to induce anti-inflammatory and antioxidant effects. RGFP966 is a highly selective inhibitor of HDAC3. This study aimed to investigate the antidepressant effect of RGFP966 on lipopolysaccharide (LPS)-induced depressive-like behaviors in mice and to explore its possible mechanism. Adult male C57BL/6J mice were utilized in this study. The LPS and RGFP966 were injected intraperitoneally daily for 5 days. The behavior tests were performed to elucidate the depression-like behaviors. Western blot, ELISA and immunofluorescence staining were used to study the HDAC3/TLR4/NLRP3 pathway-related proteins. The results of behavioral tests showed that RGFP966 could improve the LPS-induced depressive-like behaviors in mice. The results of Western blotting showed that RGFP966 treatment downregulated the expression levels of toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3), caspase-1, and interleukin-1ß (IL-1ß) (P < 0.05). Furthermore, the results of immunofluorescence staining showed that RGFP966 treatment inhibited microglial activation in the hippocampus of mice (P < 0.01). These findings suggested that RGFP966 could effectively ameliorate LPS-induced depressive-like behaviors in mice by inhibiting neuroinflammation and microglial activation. The anti-inflammatory mechanism of RGFP966 might be related to the inhibition of the HDAC3/TLR4/NLRP3 signaling pathway. Therefore, inhibition of HDAC3 using RGFP966 could serve as a potential treatment strategy for depression.

Scutellarin protects against lipopolysaccharide-induced behavioral deficits by inhibiting neuroinflammation and microglia activation in rats.

Depression is a complex and heterogeneous mental disorder. Yet, the mechanisms behind depression remain elusive. Increasing evidence suggests that inflammatory reaction and microglia activation are involved in the pathogenesis of depression. Scutellarin has been found to have anti-inflammatory and antioxidant effects in various diseases. The aim of the present study was to investigate the anti-depressant effects and potential mechanism of scutellarin in the lipopolysaccharide (LPS)-induced depression animal model. The behavioral tests showed that scutellarin administration ameliorated LPS-induced depressive-like behaviors. Additionally, the scutellarin treatment inhibited reactive oxygen species (ROS) generation. Western blot analysis results showed that scutellarin pretreatment suppressed LPS-induced the protein levels of NLRP3, caspase-1, and IL-1ß. Furthermore, immunostaining results showed that scutellarin pretreatment inhibited LPS-induced microglia activation in the hippocampus of rats. These findings suggest that scutellarin effectively improves LPS-induced inflammation-related depressive-like behaviors by inhibiting LPS-induced neuroinflammation and microglia activation, possibly via regulation of the ROS/NLRP3 signaling pathway and microglia activation. Thus, scutellarin may serve as a potential therapeutic strategy for depression.

Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/NLRP3 signaling in rat.

BACKGROUND: Recently, depression has been identified as a prevalent and severe mental disorder. However, the mechanisms underlying the depression risk remain elusive. The neuroinflammation and NLRP3 inflammasome activation are known to be involved in the pathology of depression. Dihydrolipoic acid (DHLA) has been reported as a strong antioxidant and exhibits anti-inflammatory properties in various diseases, albeit the direct relevance between DHLA and depression is yet unknown. The present study aimed to investigate the preventive effect and potential mechanism of DHLA in the lipopolysaccharide (LPS)-induced sickness behavior in rats. METHODS: Adult male Sprague-Dawley rats were utilized. LPS and DHLA were injected intraperitoneally every 2 days and daily, respectively. Fluoxetine (Flu) was injected intraperitoneally daily. PD98059, an inhibitor of ERK, was injected intraperitoneally 1 h before DHLA injection daily. Small interfering ribonucleic acid (siRNA) for nuclear factor erythroid 2-like (Nrf2) was injected into the bilateral hippocampus 14 days before the DHLA injection. Depression-like behavior tests were performed. Western blot and immunofluorescence staining detected the ERK/Nrf2/HO-1/ROS/NLRP3 pathway-related proteins. RESULTS: The DHLA and fluoxetine treatment exerted preventive effects in LPS-induced sickness behavior rats. The DHLA treatment increased the expression of ERK, Nrf2, and HO-1 but decreased the ROS generation levels and reduced the expression of NLRP3, caspase-1, and IL-1ß in LPS-induced sickness behavior rats. PD98059 abolished the effects of DHLA on preventive effect as well as the levels of Nrf2 and HO-1 proteins. Similarly, Nrf2 siRNA reversed the preventive effect of DHLA administration via the decreased expression of HO-1. CONCLUSIONS: These findings suggested that DHLA exerted a preventive effect via ERK/Nrf2/HO-1/ROS/NLRP3 pathway in LPS-induced sickness behavior rats. Thus, DHLA may serve as a potential therapeutic strategy for depression.

The arousal effect of hyperbaric oxygen through orexin/hypocretin an upregulation on ketamine/ethanol-induced unconsciousness in male rats.

Approaches that facilitate the recovery from coma would have enormous impacts on patient outcomes and medical economics. Orexin-producing neurons release orexins (also known as hypocretins) energy-dependently to maintain arousal. Hyperbaric oxygen (HBO) could increase ATP levels by preserving mitochondrial function. We investigated, for the first time, the arousal effects of HBO and orexins mechanisms in a rat model of unconsciousness induced by ketamine or ethanol. A total of 120 Sprague-Dawley male rats were used in this study. Unconsciousness was induced either by intraperitoneal injection of ketamine or ethanol. The HBO treatment (100% O2 at 3 ATA) was administered immediately after unconsciousness induction for 1 hr. SB334867, orexin-1 receptor (OX1R) inhibitor, or JNJ10397049, orexin-2 receptor (OX2R) inhibitor was administered 30 min intraperitoneally before unconsciousness induction. Loss of righting reflex test (LORR) and Garcia test were used to evaluate the unconsciousness duration and neurological deficits after recovering from unconsciousness, respectively. Enzyme-linked immunosorbent assay was used to measure brain tissue ATP and orexin A levels. Ketamine or ethanol injection resulted in LORR immediately and neurological deficits 6 hr after unconsciousness induction. HBO treatment significantly reduced the LORR duration, improved Garcia scores and unregulated ATP and orexin A levels in the brain tissue. Administration of OX1R inhibitor or OX2 R inhibitor abolished arousal and neurological benefits of HBO. In conclusion, HBO exerted arousal-promoting effects on unconscious rats induced by ketamine or ethanol. The underlying mechanism was via, at least in part, ATP/orexin A upregulation. HBO may be a practical clinical approach to accelerate unconsciousness recovery in patients.

Prefrontoparietal dysfunction during emotion regulation in anxiety disorder: a meta-analysis of functional magnetic resonance imaging studies.

OBJECTIVE: Impairments in emotion regulation, and more specifically in cognitive reappraisal, are thought to play a key role in the pathogenesis of anxiety disorders. However, the available evidence on such deficits is inconsistent. To further illustrate the neurobiological underpinnings of anxiety disorder, the present meta-analysis summarizes functional magnetic resonance imaging (fMRI) findings for cognitive reappraisal tasks and investigates related brain areas. METHODS: We performed a comprehensive series of meta-analyses of cognitive reappraisal fMRI studies contrasting patients with anxiety disorder with healthy control (HC) subjects, employing an anisotropic effect-size signed differential mapping approach. We also conducted a subgroup analysis of medication status, anxiety disorder subtype, data-processing software, and MRI field strengths. Meta-regression was used to explore the effects of demographics and clinical characteristics. Eight studies, with 11 datasets including 219 patients with anxiety disorder and 227 HC, were identified. RESULTS: Compared with HC, patients with anxiety disorder showed relatively decreased activation of the bilateral dorsomedial prefrontal cortex (dmPFC), bilateral dorsal anterior cingulate cortex (dACC), bilateral supplementary motor area (SMA), left ventromedial prefrontal cortex (vmPFC), bilateral parietal cortex, and left fusiform gyrus during cognitive reappraisal. The subgroup analysis, jackknife sensitivity analysis, heterogeneity analysis, and Egger's tests further confirmed these findings. CONCLUSIONS: Impaired cognitive reappraisal in anxiety disorder may be the consequence of hypo-activation of the prefrontoparietal network, consistent with insufficient top-down control. Our findings provide robust evidence that functional impairment in prefrontoparietal neuronal circuits may have a significant role in the pathogenesis of anxiety disorder.

Prevalence of Stroke and Vascular Risk Factors in China: a Nationwide Community-based Study.

We aimed to investigate the prevalence of stroke and related vascular risk factors in adult population aged 40 years and older in China. We conducted a prospective cross-sectional survey in nationally representative sample of 207323 individuals from all 31 Chinese provinces in 2013. Data were used to analyze the prevalence of stroke by age, sex, geographical regions and educational level. The age-standardized prevalence of stroke was significantly higher in men than in women in all age groups (P < 0.001). The age-standardized prevalence of stroke was significantly higher in rural than in urban residents among both men and women (P < 0.001). The prevalence of stroke was inversely associated with educational level. There were striking geographical variations in stroke prevalence in China with a higher prevalence of stroke in northern provinces as compared with southern provinces of the country. The age-standardized prevalence of hypertension, diabetes, dyslipidemia, atrial fibrillation and obesity in the Chinese population aged 40 years and older were 35.24%, 9.55%, 58.72%, 1.57% and 4.09%, respectively. Stroke and related vascular risk factors remains a major public threat in China and effective primary preventive strategies that aimed at reducing the burden of stroke and its risk factors are urgently needed.

Remote Ischemic Conditioning Improves Cognitive Function During Cerebral Vascular Injury Through the Induction of Autophagy.

BACKGROUND: The most valid model for vascular cognitive impairment (VCI) is the mouse bilateral common carotid artery stenosis (BCAS), whose behavioral outcomes are supposedly affected by the remote ischemic conditioning (RIC) through the induction of autophgy. We hope to determine whether RIC contributes to the neuroprotection through the induction of autophagy. METHODS: Wastar male mice were randomized into three groups including the Sham, the BCAS and the RIC+BCAS groups. All the animals were submitted to 4 cycles of 5 min occlusion and 5 min reperfusion of both the femoral vessels performing RIC. Then the animal behaviors were recorded as well as the expression of proteins and the mRNA levels. Notably, the expression of proteins relates to autophagy. By this means, it is possible to estimate the cell death, the severity of pathology and the expression of proteins under different groups. RESULTS: Compared with the sham group, the expression of proteins increased for ATG7, Beclin-1, LC3, ATG5-ATG12 while decreased for P62 in the BCAS group. These changes were further promoted in the RIC+BCAS group, which indicates that the RIC can improve the cognitive function in the BCAS group. Moreover, RT-PCR demonstrated that the mRNA level of BECN1, Atg5, Atg7 in white matter (WM) and Hippocampus in BCAS group was higher than the sham group, while it was much greater in the RIC+BCAS group. This confirmed that the autophagy was activated in the BCAS and the RIC+BCAS groups, especially the RIC+BCAS group. CONCLUSION: Improved cognition during vascular injury and RIC was associated with increased activity of autophagy.

Hyperbaric Oxygen Reduces Infarction Volume and Hemorrhagic Transformation Through ATP/NAD+/Sirt1 Pathway in Hyperglycemic Middle Cerebral Artery Occlusion Rats.

BACKGROUND AND PURPOSE: Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO). METHODS: After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion. Immediately after it, rats were exposed to HBO at 2 atmospheres absolutes for 1 hour. ATP synthase inhibitor oligomycin A, nicotinamide phosphoribosyl transferase inhibitor FK866, or silent mating type information regulation 2 homolog 1 siRNA was administrated for interventions. Infarct volume, hemorrhagic volume, and neurobehavioral deficits were recorded; the level of blood glucose, ATP, and nicotinamide adenine dinucleotide and the activity of nicotinamide phosphoribosyl transferase were monitored; the expression of silent mating type information regulation 2 homolog 1, acetylated p53, acetylated nuclear factor-κB, and cleaved caspase 3 were detected by Western blots; and the activity of matrix metalloproteinase-9 was assayed by zymography. RESULTS: Hyperglycemia deteriorated energy metabolism and reduced the level of ATP and nicotinamide adenine dinucleotide and exaggerated hemorrhagic transformation, blood-brain barrier disruption, and neurological deficits after middle cerebral artery occlusion. HBO treatment increased the levels of the ATP and nicotinamide adenine dinucleotide and consequently increased silent mating type information regulation 2 homolog 1, resulting in attenuation of hemorrhagic transformation, brain infarction, as well as improvement of neurological function in hyperglycemic middle cerebral artery occlusion rats. CONCLUSIONS: HBO induced activation of ATP/nicotinamide adenine dinucleotide/silent mating type information regulation 2 homolog 1 pathway and protected blood-brain barrier in hyperglycemic middle cerebral artery occlusion rats. HBO might be promising approach for treatment of acute ischemic stroke patients, especially patients with diabetes mellitus or treated with r-tPA (recombinant tissue-type plasminogen activator).

The role of C/EBPβin the inflammatory reaction mechanism of neurodegenerative diseases / 中华行为医学与脑科学杂志

To investigate the effect of C/EBP βon the neuroinflammation.Recently,neuroinflamma-tion research mainly focused on C/EBP β,more and more researches indicated that C/EBP βmay play an important role in neurodegenerative diseases.We searched the published papers in PubMed,CNKI,and Wan Fang date bases in June 2015.The key words were used asCCAAT enhancer binding protein beta,Neu-ron,Neuroinflammationand so on.According to the inclusion and exclusion criteria, we summaried and analyzed the literatures.Eventually,42 articles were adapted,most of which were foused on the functions and mechanisms of C/EBP βin neuroinflammation.C/EBP βparticipate in multiple signaling pathways of neu-roinflammation,and the regulation mechanism is complicated.Abrogation of C/EBPβexpression or its down-regulation by gene regulation may may serve as a therapeutic target to attenuate deleterious effects in neural tissue and ultimately prevent the development of neurodegenerative disorders.

Hyperbaric oxygen preconditioning attenuates hemorrhagic transformation through increasing PPARγ in hyperglycemic MCAO rats.

Hyperbaric oxygen preconditioning (HBO-PC) has been demonstrated to attenuate hemorrhagic transformation (HT) after middle cerebral artery occlusion (MCAO) in hyperglycemic rats. However, the mechanisms remain to be illustrated. Recently, HBO-PC has been shown to activate peroxisome proliferator-activated receptor-gamma (PPARγ) by increasing 15d-PGJ2 in primary cultured neurons. We hypothesize that HBO-PC reduces HT by suppressing inflammation through increasing 15d-PGJ2 and activating PPARγ in hyperglycemic MCAO rats. HBO (2.5ATA) was administered for 1h daily for 5 consecutive days. The PPARγ inhibitor GW9662 was administered intraperitoneally to designated animals. Infarction volume, hemorrhage volume, neurological scores and mortality were analyzed. The levels of 15d-PGJ2, PPARγ, TNF-α and IL-1ß, tight junction proteins as well as the activity of MMP-2 and MMP-9 were evaluated 24h after MCAO. HBO-PC reduced HT, improved neurological function, down-regulated inflammatory molecules and inhibited the activation of MMP-9 by increasing 15d-PGJ2 and PPARγ at 24h after MCAO. The results suggested that HBO-PC might be an alternative measure to decrease HT in ischemic stroke.

Follistatin-like 1 attenuates apoptosis via disco-interacting protein 2 homolog A/Akt pathway after middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: Follistatin-like 1 (FSTL1), an extracellular glycoprotein, has been reported to decrease apoptosis in ischemic cardiac diseases, but its effect in ischemic stroke has not been examined. We hypothesized that recombinant FSTL1 attenuates neuronal apoptosis through its receptor disco-interacting protein 2 homolog A (DIP2A) and the Akt pathway after middle cerebral artery occlusion (MCAO) in rats. METHODS: One hundred forty male Sprague-Dawley rats were subjected to 2 hours of MCAO followed by reperfusion. In a subset of animals, the time course and location of FSTL1 and DIP2A were detected by Western blot and immunofluorescence double staining. Another set of animals were intracerebroventricularly given either recombinant FSTL1 1 hour after reperfusion or FSTL1-small interfering RNA (siRNA) 48 hours before reperfusion. Additionally, DIP2A was knockdown by siRNA in some animals. Infarction volume and neurological deficits were measured, and the expression of FSTL1, DIP2A, phosphorylated Akt, cleaved caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labeling were quantified using Western blot. RESULTS: The expression of FSTL1 and DIP2A was increased in neurons and peaked 24 hours after MCAO. Recombinant FSTL1 reduced brain infarction and improved neurological deficits 24 and 72 hours after MCAO via activation of its receptor DIP2A and downstream phosphorylation of Akt. These effects were reversed by DIP2A-siRNA and FSTL1-siRNA. CONCLUSIONS: Recombinant FSTL1 decreases neuronal apoptosis and improves neurological deficits through phosphorylation of Akt by activation of its receptor DIP2A after MCAO in rats. Thus, FSTL1 may have potentials as a treatment for patients with ischemic stroke.

Impairment in preattentive processing among patients with hypertension revealed by visual mismatch negativity.

OBJECTIVE: Patients with hypertension show deficits in cognitive function. However, the neural mechanisms underlying the preattentive information processing in hypertensive patients are poorly understood. We seek to investigate whether hypertensive patients have impairments in preattentive information processing. METHODS: We compared visual mismatch negativity (vMMN) between 15 hypertensive patients and 15 age-matched healthy controls, which was elicited by the change of visual duration randomly presented in both peripheral visual fields. In addition, the global cognitive function for all participants was assessed with Mini-Mental State Examination (MMSE). RESULTS: The vMMN in deviant-standard comparison was observed at occipital-temporal regions. Compared with normal healthy controls, the amplitude of vMMN was significantly decreased in hypertensive patients (P < 0.05). Meanwhile, the vMMN peak latency was delayed in the hypertensive group (P < 0.05). However, the MMSE scores of patients with hypertension were not significantly different from those of controls (P > 0.05), and there was no significant correlation between the mean amplitude of vMMN and SBP, DBP, and MMSE in hypertensive individuals, respectively. CONCLUSIONS: These data indicate dysfunction of automatically change detection processing in patients with hypertension. Moreover, the changes of vMMN provide a more objective and reliable assessment for cognitive impairment in hypertensive patients.

Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.

INTRODUCTION: Neurogenic pulmonary edema (NPE) is an acute and serious complication after subarachnoid hemorrhage (SAH) with high mortality. The present study aimed to test the therapeutic potential of brilliant blue G (BBG), a selective P2X purinoceptor 7 (P2X7R) antagonist, on NPE in a rat SAH model. METHODS: SAH was induced by endovascular perforation. 86 Sprague-Dawley rats were randomly divided into sham, vehicle-, or BBG-treatment groups. Mortality, body weight, SAH grading, neurological deficits, NPE clinical symptoms, and pulmonary index were measured at 24 hours following SAH. Western blot, gelatin zymography, lung histopathology, and immunofluorescence staining were performed in the left lung lobe to explore the underlying mechanisms at 24 hours post-surgery. RESULTS: The incidence of clinical symptoms was correlated with pulmonary index. P2X7R and the marker of alveolar type I epithelial cells (the mucin-type glycoprotein T1-α) immunoreactivities were generally co-localized. BBG administration decreased mature interleukin-1ß, myeloperoxidase, and matrix metallopeptidase-9 activation, but increased tight junction proteins, such as ZO-1 and occludin, which ameliorated pulmonary edema via anti-inflammation and improved neurological deficits. CONCLUSION: P2X7R inhibition prevented NPE after SAH by attenuating inflammation. Thus, BBG is a potential therapeutic application for NPE after SAH and warrants further research.