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BACKGROUND Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke that mainly affects the young. Anticoagulation (AC) with heparin is the mainstay of treatment for CVST. Although highly anticipated, endovascular therapy (ET) including local thrombolysis and mechanical thrombectomy has been controversial. REVIEW SUMMARY To compare the effectiveness and safety of ET with AC for patients with confirmed CVST, we systematically searched PubMed, Embase, and Cochrane Library from the earliest date to February 2020. Data on the total number of patients in each treatment group and the exact number of patients for each outcome were separately extracted from 10 studies with 891 patients.Our Results show that ET has a higher mortality rate compared with AC [odds ratio (OR)=1.95; 95% confidence interval (CI), 1.19-3.18; P=0.008

BackgroundSex differences affect the occurrence, progression and regression of subarachnoid haemorrhage (SAH). Oestrogen plays a protective role in alleviating the vasospasm and neuronal apoptosis induced by SAH. However, whether oestrogen affects blood‒brain barrier (BBB) integrity has not been fully studied. Oestrogen has been found to regulate the sonic hedgehog (SHH) signalling pathway through the oestrogen receptor in gastric cancer and adrenal glands, and the SHH signalling pathway has an important role in maintaining the BBB by upregulating the expression of tight junction proteins. In this study, we investigated the relationship between oestrogen and the SHH signalling pathway using clinical data and established an experimental SAH model to explore whether oestrogen could ameliorate BBB damage after SAH through the SHH pathway.MethodsCorrelations between oestrogen and the SHH pathway were analysed by patients’ cerebrospinal fluid (CSF) samples and the Genotype-Tissue Expression database (GTEx). Then, an experimental rat SAH model was established using the endovascular perforation method and treated with oestrogen, oestrogen inhibitors and SHH signalling pathway inhibitors. Then, the effects of oestrogen on BBB damage were analysed by western blot, immunofluorescence and neurobehavioural experiments.ResultsESLIA detection and correlation analysis showed that oestrogen levels in patients’ CSF were positively correlated with the SHH pathway, which was further verified by GTEx gene-correlation analysis. SHH was found to be mainly expressed in neurons and astrocytes in rats under physiological conditions and was upregulated by oestrogen pretreatment. In the SAH model, oestrogen pretreatment was found to reverse SAH-induced decreases in the SHH pathway, which were counteracted by oestrogen receptor inhibitors. Furthermore, oestrogen pretreatment reduced SAH-induced BBB damage, brain oedema and neurological dysfunction, which were eliminated by SHH pathway inhibitors.ConclusionIn conclusion, we demonstrate here that oestrogen pretreatment ameliorates brain injury after SAH, at least in part through SHH pathway-mediated BBB protection.

Solriamfetol is developed for the treatment of excessive sleepiness in adult patients with narcolepsy and obstructive sleep apnea (OSA). No systematic review of existing literature has been investigated before. Therefore, the meta-analysis is conducted to assess the efficacy and safety of solriamfetol for excessive sleepiness in narcolepsy and OSA.PubMed, Embase and Cochrane Library databases were searched from earliest date to July 2020 for randomized controlled trials (RCTs) and the primary outcomes were change from baseline in mean sleep latency and Epworth Sleepiness Scale (ESS).We pooled 1177 patients from five RCTs and found solriamfetol led to a significant increment in mean sleep latency (MD = 9.52, 95% CI: 7.60 to 11.44, P 0.00001) and a reduction in ESS score (MD = -3.74, 95% CI: -4.38 to -3.09, P 0.00001) compared with placebo. The proportion of patients with at least one adverse event was significantly increased in solriamfetol group (RR = 1.42, 95% CI: 1.24 to 1.64, P 0.00001), while no statistical differences existed in the risk of at least one serious adverse event between solriamfetol and controlled group (RR = 0.95, 95% CI: 0.24 to 3.77, P = 0.39).A dose of 150 mg solriamfetol is proved to be the appropriate and stable dose for excessive sleepiness. In addition, solriamfetol showed good efficacy for excessive sleepiness in narcolepsy and OSA but also significantly increases the risk of adverse events.

Intracerebral hemorrhage (ICH), the most lethal type of stroke, often leads to poor outcomes in the clinic. Due to the complex mechanisms and cell-cell crosstalk during ICH, the neurovascular unit (NVU) was proposed to serve as a promising therapeutic target for ICH research. This review aims to summarize the development of pathophysiological shifts in the NVU and neural-glia networks after ICH. In addition, potential targets for ICH therapy are discussed in this review. Beyond cerebral blood flow, the NVU also plays an important role in protecting neurons, maintaining central nervous system (CNS) homeostasis, coordinating neuronal activity among supporting cells, forming and maintaining the blood-brain barrier (BBB), and regulating neuroimmune responses. During ICH, NVU dysfunction is induced, along with neuronal cell death, microglia and astrocyte activation, endothelial cell (EC) and tight junction (TJ) protein damage, and BBB disruption. In addition, it has been shown that certain targets and candidates can improve ICH-induced secondary brain injury based on an NVU and neural-glia framework. Moreover, therapeutic approaches and strategies for ICH are discussed.

Esketamine is a promising drug which can induce antidepressant effects in Major Depression Disorder (MDD). Several randomized controlled trials (RCTs) have been implemented to assess the efficacy and safety of esketamine for the treatment of MDD. Therefore, we carried out a meta-analysis to assess adverse effect profiles of esketamine for the treatment of MDD. We searched RCTs which were implemented from January 2010 to June 2020 by searching PubMed, Embase and Cochrane Library databases. Finally, four RCTs with 551 patients were included in our study. We pooled 551 patients from 4 RCTs. Compared with placebo, an increased risk of adverse effects was observed in our analysis. After using esketamine, the risk of nausea (RR = 2.34, 95% CI, 1.04 to 5.25, P = 0.04), dissociation (RR = 4.54, 95% CI, 2.36 to 8.73, P P P = 0.0002), hypoesthesia (RR = 5.68, 95% CI, 2.06 to 15.63, P = 0.0008), sedation (RR = 3.96, 95% CI, 1.29 to 12.15, P = 0.02) and paresthesia(RR = 3.05, 95% CI, 1.07 to 8.65, P = 0.04)were significantly increased compared with placebo. Our synthesized data analysis revealed drug specific risk profiles. The most frequent adverse effects under treatment with esketamine were nausea, dissociation, dizziness, vertigo, hypoesthesia,sedation and paresthesia.

The infiltration of blood components into the brain parenchyma through the lymphoid system is an important cause of subarachnoid hemorrhage injury. AQP4, a water channel protein located at the astrocyte foot, has been reported to regulate blood–brain barrier integrity, and its polarization is disrupted after SAH. Neuronal ferroptosis is involved in subarachnoid hemorrhage- (SAH-) induced brain injury, but the inducing factors are not completely clear. Transferrin is one of the inducing factors of ferroptosis. This study is aimed at researching the role and mechanism of AQP4 in brain injury after subarachnoid hemorrhage in mice. An experimental mouse SAH model was established by endovascular perforation. An AAV vector encoding AQP4 with a GFAP-specific promoter was administered to mice to achieve specific overexpression of AQP4 in astrocytes. PI staining, Fer-1 intervention, and transmission electron microscopy were used to detect neuronal ferroptosis, and dextran (40 kD) leakage was used to detect BBB integrity. Western blot analysis of perfused brain tissue protein samples was used to detect transferrin infiltration. First, neuronal ferroptosis 24 h after SAH was observed by PI staining and Fer-1 intervention. Second, a significant increase in transferrin infiltration was found in the brain parenchyma 24 h after SAH modeling, while transferrin content was positively correlated with neuronal ferroptosis. Then, we observed that AQP4 overexpression effectively improved AQP depolarization and BBB injury induced by SAH and significantly reduced transferrin infiltration and neuronal ferroptosis after SAH. Finally, we found that AQP4 overexpression could effectively improve the neurobehavioral ability of SAH mice, and the neurobehavioral ability was negatively correlated with transferrin brain content. Taken together, these data indicate that overexpression of AQP4 in the mouse brain can effectively improve post-SAH neuronal ferroptosis and brain injury, at least partly by inhibiting transferrin infiltration into the brain parenchyma in the glymphatic system.

Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. Galactose lectin-9 (Gal-9) belongs to the family of β-galactoside-binding lectins, which has been shown to play a vital role in immune tolerance and inflammation. However, the function of Gal-9 in ICH has not been fully studied in details. Several experiments were carried out to explore the role of Gal-9 in the late period of ICH. Primarily, ICH models were established in male adult Sprague Dawley (SD) rats. Next, the relative protein levels of Gal-9 at different time points after ICH were examined and the result showed that the level of Gal-9 increased and peaked at the 7th day after ICH. Then we found that when the content of Gal-9 increased, both the number of M2-type microglia and the corresponding anti-inflammatory factors also increased. Through co-immunoprecipitation (CO-IP) analysis, it was found that Gal-9 combines with Toll-like receptor-4 (TLR-4) during the period of the recovery after ICH. TUNEL staining and Fluoro-Jade B staining (FJB) proved that the amount of cell death decreased with the increase of Gal-9 content. Additionally, several behavioral experiments also demonstrated that when the level of Gal-9 increased, the motor, sensory, learning, and memory abilities of the rats recovered better compared to the ICH group. In short, this study illustrated that Gal-9 takes a crucial role after ICH. Enhancing Gal-9 could alleviate brain injury and promote the recovery of ICH-induced injury, so that Gal-9 may exploit a new pathway for clinical treatment of ICH.

As one kind of disease-modifying therapies, sphingosine-1-phosphate receptor (S1PR) modulators such as fingolimod, ozanimod, and siponimod have been approved or are being developed to treat multiple sclerosis (MS). Several randomized controlled trials (RCT) have been implemented to compare the efficacy and safety of S1PR modulators versus interferon beta in the treatment of people with relapsing-remitting multiple sclerosis (RRMS).We searched RCTs which were implemented from January 2010 to June 2020 by searching PubMed, Embase, Cochrane Library databases, and the Central Register of Controlled Trials. Finally, five RCTs were included in our study after carefully choosing.We pooled 4304 patients from 5 RCTs. The primary outcome was the annualized relapse rate. We found that the annualized relapse rate in the S1PR modulator group is 20% less than that in the interferon beta group (95%CI, - 0.32 to - 0.07, P = 0.002). S1PR modulators led to a significant reduction in number of new or enlarging T2 lesions per scan and number of gadolinium-enhancing lesions compared with interferon beta. Moreover, S1PR modulators can also improve 54-item multiple sclerosis quality of life (MSQOL-54) physical health composite score (P = 0.0005).S1PR modulators exhibited good efficacy and safety for the treatment of RRMS compared with interferon beta. According to follow-up trials, S1PR modulators can improve MSQOL-54 physical health composite score so that it may be beneficial to neurological recovery which need more research to confirm.

Objectives To identify clinical characteristics of severe patients with COVID-19. Methods The WHO database of publications on COVID-19 and PubMed were searched from inception to March 20, 2020 and all valuable studies were analyzed using Stata 15.0. Results We selected forty-four studies with 13,497 patients. In the comparison of severe and non-severe groups, age over 50 (OR = 4.090; 95% CI = 2.422–6.907, P = 0.000) and underlying disease (OR = 3.992; 95% CI = 2.631–6.507, P = 0.000) are risk factors. Female gender (OR = 0.740; 95% CI = 0.622–0.881, P = 0.001) is a protective factor. Characteristics like dyspnea (OR = 4.914; 95% CI = 3.069–7.867, P = 0.000), lymphopenia (OR = 5.528; 95% CI = 3.484–8.772, P = 0.000), thrombocytopenia (OR = 3.623; 95% CI = 1.034–12.691, P = 0.044), elevated C-reactive protein (OR = 5.217; 95% CI = 2.459–11.070, P = 0.000) and D-dimer (OR = 3.780; 95% CI = 1.481–9.648, P = 0.005) were more frequently in severe cases. Diffuse lesions and consolidation (OR = 4.680; 95% CI = 3.183–6.881, P = 0.000) in imaging was considered reliable. Conclusions Men older than 50 with underlying disease are susceptible to develop severe pneumonia while female gender is protective. The typical symptom of severe pneumonia was dyspnea, but high fever, headache and diarrhea were not significantly different among patients with varying degrees of severity. Lymphopenia, thrombocytopenia, elevated C-reactive protein and D-dimer occurred more frequently in severe patients and yet leukopenia is not a characteristic laboratory indicator. Diffuse lesions and consolidation are important imaging features to distinguish severe pneumonia.

Background Some studies have reported that women are at higher risk for spontaneous subarachnoid hemorrhage (SAH) compared with men, and smoking is the most important lifestyle risk factor for spontaneous SAH. However, it is still unknown whether the risk of SAH from smoking and smoking status is differential for women and men. We performed a meta-analysis to estimate the effect of smoking on SAH in women compared with men. Methods PubMed (January 1, 1966 to February 19, 2020) and EMBASE (January 1, 1980 to February 19, 2020) were systematically searched. Studies that estimated sex-specific relative risks (RRs) of SAH were selected. We pooled sex-specific RRs, comparing women with men using random-effects meta-analysis. Results Data from 20 observational studies that included 1,387,204 participants (563,898 women) and 7,838 SAHs (3,977 women) were analyzed. The combined women-to-men RRs of former smokers versus never smokers for SAH were 1.08 (95% confidence interval [CI] 0.62–1.89, p = 0.78). The pooled women-to-men RRs of current smokers versus never smokers were 1.39 (95% CI 1.05–1.83, p = 0.02). The combined women-to-men RRs of total smokers versus never smokers RRs were 1.15 (95% CI 0.88–1.52, p = 0.30). Conclusions Our study shows there is not enough evidence to suggest that women who smoke have a greater risk for SAH than men; however, women who persistently smoke have a greater risk. Smoking seems to be more susceptible in the increased SAH risk in women.

The activation of microglia and inflammatory responses is essential for the process of intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). In this study, we investigated the effects of luteolin on ICH-induced SBI and the potential mechanisms. Autologous blood was injected to establish the ICH model in vivo, and oxyhemoglobin (OxyHb) was used to mimic the ICH model in vitro. We found that the administration of luteolin significantly improved motor and sensory impairments and inhibited neuronal cell degeneration in vivo. In the in vitro study, the decrease of the neuronal cell viability induced by activated microglia was alleviated by luteolin treatment. Furthermore, by antagonizing the activation of the Toll-like receptor 4 (TLR4)/TNF receptor-associated factor 6 (TRAF6)/nuclear transcription factor-κB (NF-κB) signaling pathway, the ICH-induced elevation of cytokine release was decreased after treatment with luteolin, which was confirmed both in vivo and in vitro. Additionally, we found that luteolin engaged with TRAF6 and inhibited the ubiquitination of TRAF6. Taken together, our findings demonstrate the neuroprotective effects of luteolin after ICH and the potential mechanisms, which suggest that luteolin is a potential therapeutic candidate for ICH treatment.

Excessive daytime sleepiness is considered as the prominent symptom in narcolepsy and Obstructive Sleep Apnea (OSA). Pitolisant is a novel selective histamine H3 receptor antagonist approved for improving excessive daytime sleepiness. The meta-analysis is conducted to assess the efficacy and safety of pitolisant versus placebo for excessive daytime sleepiness in narcolepsy and OSA. PubMed, Embase and Cochrane Library databases were searched from earliest date to November 2020 for randomized controlled trials (RCTs). The primary outcomes were mean changes in Epworth Sleepiness Scale (ESS), mean sleep latency, European quality-of-life questionnaire (EQ-5D), and risk ratio of treatment-emergent adverse events (TEAEs). We pooled 678 patients from four RCTs and found pitolisant significantly decreased ESS by mean difference (MD) of − 2.86 points (95% CI: − 3.75 to − 1.96), increased mean sleep latency by MD of 3.14 min (95% CI: 2.18–4.11), and increased EQ-5D by MD of 3.32 points (95% CI: 0.26–6.39) compared with placebo. The risk ratio of TEAE was 1.37 (95% CI: 1.08–1.74). Insomnia was the only TEAE significantly associated with pitolisant treatment. In conclusion, pitolisant showed great efficacy and controllable security versus placebo for excessive daytime sleepiness in narcolepsy and OSA. Compared with narcolepsy, patients with OSA were deemed to benefit more from pitolisant especially in terms of improving mobility and quality of life of patients without continuous positive airway pressure therapy.