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Acute stroke is one of the leading causes of morbidity and mortality worldwide. Stroke-induced immune-inflammatory response occurs in the perilesion areas and the periphery. Although stroke-induced immunosuppression may alleviate brain injury, it hinders brain repair as the immune-inflammatory response plays a bidirectional role after acute stroke. Furthermore, suppression of the systemic immune-inflammatory response increases the risk of life-threatening systemic bacterial infections after acute stroke. Therefore, it is essential to explore the mechanisms that underlie the stroke-induced immune-inflammatory response. Autonomic nervous system (ANS) activation is critical for regulating the local and systemic immune-inflammatory responses and may influence the prognosis of acute stroke. We review the changes in the sympathetic and parasympathetic nervous systems and their influence on the immune-inflammatory response after stroke. Importantly, this article summarizes the mechanisms on how ANS regulates the immune-inflammatory response through neurotransmitters and their receptors in immunocytes and immune organs after stroke. To facilitate translational research, we also discuss the promising therapeutic approaches modulating the activation of the ANS or the immune-inflammatory response to promote neurologic recovery after stroke. © 2022 American Physiological Society. Compr Physiol 12:3665-3704, 2022.

The objective of this research is to study the effect of obstructive sleep apnea-hypopnea syndrome on cognitive function of stroke. Based on linear regression equation and Montreal Cognitive Assessment Scale, the degree of cognitive impairment in OSAHS patients was evaluated and the influencing factors of OSAHS-induced cognitive impairment and the correlation between the degree of OSAHS and cognitive impairment were explored. The results are as follows: about 68% of OSAHS patients have cognitive dysfunction, and the incidence of cognitive dysfunction is positively correlated with OSAHS; cognitive impairment of OSAHS patients was associated with age, obesity, years of schooling, and intermittent nocturnal hypoxia or hypoventilation; the severity of cognitive dysfunction of OSAHS patients was positively correlated with age and obesity but negatively correlated with education level; Logistic regression analysis results showed that there were three factors that were finally entered into the regression equation, namely, LSaO2, BMI, and AHI, and the Logistic regression equation obtained was as follows: Logist P = − 0.109 X 1 + 0.785 X 2 + 1.228 X 3 . This study helps clinical workers to detect and intervene the impaired cognitive ability of patients with OSAHS early, so as to reduce the incidence and mortality of related complications and improve the quality of life of patients.

Background/Objective: AD-associated PSEN1 mutations exhibit high clinical heterogeneity. The discovery of these mutations and the analysis of their associations with cases such as EOAD should be critical to understand the pathogenesis of AD. Methods: We performed clinical analysis, neuroimaging, target region capture and high-throughput sequencing, and Sanger sequencing in a family of 3 generations. The underlying Alzheimer’s pathology was evaluated by using biomarker evidence obtained from cerebrospinal fluid (CSF) amyloid testing and 18F-florbetapir (AV-45) PET imaging. Results: Target region capture sequencing revealed a novel heterozygous C to T missense point mutation at the base position 284 (c.850 C＞T,) located in exon 8 of the PSEN1 gene, resulting in a Proline-to-Serine substitution (P284S) at codon position 850. The mutation was also identified by Sanger sequencing in 2 family members including proband and her daughter and was absent in the other 4 unaffected family members and 50 control subjects. Cerebrospinal fluid (CSF) amyloid test exhibited biomarker evidence of underlying Alzheimer’s pathology. 18F-florbetapir (AV-45) PET imaging indicated extensive cerebral cortex and cerebellar Aβ deposition. Conclusions: We discovered a novel PSEN1 pathogenic mutation P284S, which was observed for the first time in a Chinese family with early-onset AD.

Background The long-term complications of gestational diabetes mellitus (GDM) may be associated with the development of arthritis, particularly rheumatoid arthritis (RA) and osteoarthritis (OA). However, the possible relationship between these two conditions remains unclear, hindering our understanding of both diseases. We conducted a novel study using bidirectional two-sample Mendelian randomization to explore the potential causal bidirectional relationship between GDM and arthritis. Methods In this study, we extracted single nucleotide polymorphisms closely associated with GDM and arthritis (RA, OA) from published genome-wide association studies (GWAS) data in open databases as instrumental variables (IVs). We employed inverse variance-weighted as the main evaluation criterion, the weighted median method as a possible alternative criterion, and multiple methods as supplements to assess causal relationships. Results were presented as odds ratios (ORs). Additionally, leave-one-out sensitivity analysis, horizontal pleiotropy, and heterogeneity tests were used to verify the reliability and stability of the results. Result Our results indicate a causal association between GDM and an increased risk of arthritis (RA: OR = 4.34, 95% CI = 3.49–5.41, P = 1.96 × 10–39, OA: OR = 1.05, 95% CI = 1.02–1.07, P = 5.27 × 10− 05). In reverse MR analysis, our findings supported the promoting effect of RA on the development of GDM (OR = 1.15, 95% CI = 1.11–1.20, P = 4.44 × 10–14), while the evidence is insufficient to support the conclusion that OA affects the development of GDM (P = 0.757). The heterogeneity test, horizontal pleiotropy test, and leave-one-out sensitivity analysis demonstrated the reliability and stability of our study's results. Conclusion Our study suggests that genetically predisposed GDM increases the risk of developing arthritis (OA, RA). Additionally, genetically predisposed RA is causally associated with an increased risk of GDM. However, we did not find evidence for a causal association between genetically predisposed OA and GDM. These results contribute to a better understanding of the underlying mechanisms of GDM and arthritis. Furthermore, our study has significant potential to guide clinical management and the prevention of complications in patients with GDM and arthritis.

Background： The relationship between ankylosing spondylitis (AS) and mechanical complications of prosthesis after arthroplasty has garnered increasing attention in the medical community. However, the causal relationship between them remains unclear. We conducted a novel study utilizing a two-sample Mendelian randomization analysis to investigate the relationship between these two diseases. Methods: In this study, we obtained single-nucleotide polymorphisms (SNPs) strongly associated with AS and mechanical complications of prosthesis from summary data from genome-wide association studies (GWAS). AS was used as exposure and SNPs as instrumental variables (IVs). The causality was assessed using inverse variance weighted method, and the results were presented as odds ratios (OR). In addition, we conducted heterogeneity tests, horizontal pleiotropy tests, and sensitivity analysis to investigate the potential existence of any bias that may impact the causal relationship. Results: Our results indicate that AS has a causal effect that promotes mechanical complications of prosthesis, as assessed by the inverse variance weighted (IVW) method (OR= 1.037, 95% CI = 1.011, 1.062; P = 0.00366). Although the results of other methods such as MR Egger, weighted median, simple mode， and weighted mode showed no significant causal relationship between the two diseases (P > 0.05), the IVW results should be considered the primary criterion of causality, indicating that AS is a facilitator of mechanical complications of prosthesis. Heterogeneity tests, horizontal pleiotropy tests, and sensitivity analysis showed that these results are reliable and stable. Conclusion: In a word, the results of this Mendelian randomized study suggest that ankylosing spondylitis is associated with an increased risk of mechanical complications of prosthesis after arthroplasty. Therefore, it is recommended that AS patients undergo careful assessment and monitoring during the surgical process to minimize the risk of such complications.

A core proposition in economics is that voluntary exchanges benefit both parties. We show that people often deny the mutually beneficial nature of exchange, instead espousing the belief that one or both parties fail to benefit from the exchange. Across four studies (and 8 further studies in the online supplementary materials), participants read about simple exchanges of goods and services, judging whether each party to the transaction was better off or worse off afterward. These studies revealed that win-win denial is pervasive, with buyers consistently seen as less likely to benefit from transactions than sellers. Several potential psychological mechanisms underlying win-win denial are considered, with the most important influences being mercantilist theories of value (confusing wealth for money) and theory of mind limits (failing to observe that people do not arbitrarily enter exchanges). We argue that these results have widespread implications for politics and society. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

This study was designed to investigate the impact of the preexisting use of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) on the cellular immune response in peripheral blood and the clinical outcomes of patients with acute ischemic stroke. We retrospectively collected clinical data from a cohort of 69 patients with premorbid beta-blockers and 56 patients with premorbid ACEIs/ARBs. Additionally, we selected a cohort of 107 patients with acute ischemic stroke to be the control of the same age and sex. We analyzed cellular immune parameters in peripheral blood 1 day after the appearance of symptoms, including the frequencies of circulating white blood cell subpopulations, the neutrophil-to-lymphocyte ratio (NLR), and the lymphocyte-to-monocyte ratio (LMR). We found that the count of lymphocytes and the lymphocyte-to-monocyte ratio were significantly higher in the peripheral blood of patients treated with beta-blockers before stroke than in matched controls. However, the premorbid use of ACEIs/ARBs did not considerably impact the circulating immune parameters listed above in patients with acute ischemic stroke. Furthermore, we found that premorbid use of beta-blockers or ACEIs/ARBs did not significantly change functional outcomes in patients 3 months after the onset of stroke. These results suggest that premorbid use of beta-blockers, but not ACEIs/ARBs, reversed lymphopenia associated with acute ischemic stroke. As cellular immune changes in peripheral blood could be an independent predictor of stroke prognosis, more large-scale studies are warranted to further verify the impact of premorbid use of beta-blockers or ACEIs/ARBs on the prognosis of patients with ischemic stroke. Our research is beneficial to understanding the mechanism of the systemic immune response induced by stroke and has the potential for a therapeutic strategy in stroke interventions and treatment.

Short-term intensive insulin therapy (SIIT) is an option for individuals with type 2 diabetes (T2D) starting insulin. In the BEYOND V study in Chinese individuals with uncontrolled T2D, SIIT was administered during study run-in (prior to randomisation) using a basal-first insulin titration method.This was an exploratory analysis exclusively of the 7-10-day run-in period of BEYOND V. Participants were hospitalised and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4-0.5 units/kg/day, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4-6.1 mmol/L (79-119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4-6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets.Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG7.0 mmol/L (126 mg/dL) and 2-hour PBG10 mmol/L (180 mg/dL) and 282/396 (71.2%) had both FBG6.1 mmol/L (100 mg/dL) and 2-hour PBG10 mmol/L. Mean first time to achieve FBG7 mmol/L, 2-hour PBG10 mmol/L, and both was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia.Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.www.gov NCT03359837 This article is protected by copyright. All rights reserved.

Peng Ji,1,2,&ast; Qixing Kou,2,&ast; Jiewen Zhang3 1Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Neurology, The Third People’s Hospital of Zhengzhou (Tumor Hospital Affiliated of Henan University), Zhengzhou, People’s Republic of China; 3Department of Neurology, Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiewen Zhang, Email zhangjiewen2022@163.comPurpose: The purpose of this study was to explore the change of carotid intima-media thickness (IMT) and its correlation with inflammatory markers in patients with different degrees of obstructive sleep apnea (OSA).Methods: One hundred hospitalized patients were selected and were divided into the normal control group (21 cases), the mild-moderate group (39 cases) and the severe group (40 cases) according to their apnea hypopnea index (AHI). Carotid IMT of all registered patients was studied with ultrasound, and serum levels of high-sensitivity C-reactive protein (hs-CRP), Lipoprotein-associated phospholipaseA2 (Lp-PLA2) and tumor necrosis factor-α (TNF-α) were measured. Pearson correlation analysis and multiple stepwise regression analysis were used to analyze the correlation between carotid IMT and inflammatory factors.Results: Patients with mild, moderate and severe OSA Carotid IMT had significantly higher levels of serum hs-CRP, Lp-PLA2 and TNF-α compared with the normal control group (P < 0.001). The levels of carotid IMT, serum protein hs-CRP, Lp-PLA2 and TNF-α in the severe OSA group were significantly higher than those of the mild-moderate OSA group, with P values being less than 0.001. Carotid artery IMT was positively correlated with serum hs-CRP (r = 0.83, P < 0.001), Lp-PLA2 (r =0.58, P < 0.001), and TNF-α (r =0.69, P < 0.001). hs-CRP, TNF-α and AHI were independent factors affecting carotid artery IMT. In addition, AHI was an independent indicator of carotid atherosclerosis (P = 0.0012).Conclusion: Increased inflammatory factors in OSA patients might cause the progression of atherosclerosis, which might increase the risk of cardiovascular and cerebrovascular diseases in OSA patients.Keywords: atherosclerosis, intima-media thickness, inflammation, obstructive sleep apnea

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an early-onset inherited small vessel disease. Decreased cerebral blood flow (CBF) may contribute to white matter hyperintensity (WMH) severity in CADASIL, but more evidence is needed to support this hypothesis. This study comprised six patients with CADASIL who harbored mutations in the coding sequence of

Social media has expanded the scope and method of interpersonal communication, and presents the risk of social media addiction as well. This study reported the psychometrics of the Bergen Social Media Addiction Scale (BSMAS) and further analyzed the moderating role of peer relationship on the association between negative emotions and risk of social media addiction. A total of 1258 survey participants were asked to complete a set of scales online. Exploratory structural equation modeling enabled BSMAS to reveal a solid one-factor structure with satisfactory internal consistency coefficient. Criterion-related validity and variance explanation rate analysis implied a positive relationship between negative emotions and risk of social media addiction, and identified the significant contributions of negative emotions and peer relationship to the risk of social media addiction. Moderation analysis demonstrated that peer relationship positively moderated the effect of negative emotions on the risk of social media addiction. However, gender was not a moderator affecting negative emotions on the risk of social media addiction. BSMAS was a valid tool for measuring the risk of social media addiction among Chinese adolescents. Lastly, peer relationship is a positive moderator in influencing negative emotions and risk of social media addiction.

Glioblastomas (GBM) is the most common primary malignant brain tumor, and radiotherapy plays a critical role in its therapeutic management. Unfortunately, the development of radioresistance is universal. Here, we identified calcium-regulated heat-stable protein 1 (CARHSP1) as a critical driver for radioresistance utilizing genome-wide CRISPR activation screening. This is a protein with a cold-shock domain (CSD)-containing that is highly similar to cold-shock proteins. CARHSP1 mRNA level was upregulated in irradiation-resistant GBM cells and knockdown of CARHSP1 sensitized GBM cells to radiotherapy. The high expression of CARHSP1 upon radiation might mediate radioresistance by activating the inflammatory signaling pathway. More importantly, patients with high levels of CARHSP1 had poorer survival when treated with radiotherapy. Collectively, our findings suggested that targeting the CARHSP1/TNF-α inflammatory signaling activation induced by radiotherapy might directly affect radioresistance and present an attractive therapeutic target for GBM, particularly for patients with high levels of CARHSP1.

To explore phenotypic and mutational characteristics of a pedigree with distal hereditary motor neuropathy (dHMN).Clinical data of the proband and her family members was collected. Electrophysiology, muscle biopsy and whole exome sequencing were carried out for the proband.Patients of the family mainly presented with distal lower limb weakness. Electrophysiological test of the proband revealed distal motor neuropathy and sensory nerves were normal. Muscle biopsy suggested neurogenic atrophy of muscle fibers. Genetic analysis revealed a heterozygous c.421AG (p.K141E) mutation in exon 2 of the HSPB8 gene, which was a hot spot mutation.This family was the first reported HSPB8 related dHMN2A in Chinese population, and p.K141E was the causative mutation, which enriched the mutational spectrum of dHMN in China.

Acute intracerebral hemorrhage (ICH) is a devastating type of stroke worldwide. Neuronal destruction involved in the brain damage process caused by ICH includes a primary injury formed by the mass effect of the hematoma and a secondary injury induced by the degradation products of a blood clot. Additionally, factors in the coagulation cascade and complement activation process also contribute to secondary brain injury by promoting the disruption of the blood-brain barrier and neuronal cell degeneration by enhancing the inflammatory response, oxidative stress, etc. Although treatment options for direct damage are limited, various strategies have been proposed to treat secondary injury post-ICH. Perihematomal edema (PHE) is a potential surrogate marker for secondary injury and may contribute to poor outcomes after ICH. Therefore, it is essential to investigate the underlying pathological mechanism, evolution, and potential therapeutic strategies to treat PHE. Here, we review the pathophysiology and imaging characteristics of PHE at different stages after acute ICH. As illustrated in preclinical and clinical studies, we discussed the merits and limitations of varying PHE quantification protocols, including absolute PHE volume, relative PHE volume, and extension distance calculated with images and other techniques. Importantly, this review summarizes the factors that affect PHE by focusing on traditional variables, the cerebral venous drainage system, and the brain lymphatic drainage system. Finally, to facilitate translational research, we analyze why the relationship between PHE and the functional outcome of ICH is currently controversial. We also emphasize promising therapeutic approaches that modulate multiple targets to alleviate PHE and promote neurologic recovery after acute ICH.

Earthquake stress drop is an important source parameter that directly links to strong ground motion and fundamental questions in earthquake physics. Stress drop estimations may contain significant ...

Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer’s disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer’s disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer’s disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10−19, 2.49 × 10−23, 1.35 × 10−67, and 4.81 × 10−9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P, Jia et al. identify novel Alzheimer’s disease-related variants in a two-stage genome-wide association study in a Chinese population, and use the variants to build 11 predictive models. Validation of the models in a separate longitudinal cohort confirms that they can predict Alzheimer's disease risk.

Objective: Bone marrow mononuclear cells (BMMCs) are considered a potential approach to promote the recovery of stroke-induced neurological deficit. However, the exact mechanism of BMMCs in nerve function recovery is still unclear. Methods: Adult Sprague-Dawley (SD) rat models of cerebral ischemia-reperfusion injury was established by using thread method. BMMCs were transplanted into rat models. Neurological deficits were evaluated by Longa score scale. Immunohistochemistry assay were employed to examine the expression of GFAP and Nogo-A around the ischemic foci in the right frontal lobe. Caspase-3 activity was examined by Western Blot. Results: Rats in BMMCs group had lessened neurological deficits and cleaved Caspase-3 expression on day 21 after reper-fusion, as well as higher expression of GFAP [(37.62±2.45) vs. (27.62±1.69) and (38.00±1.85) vs. (27.25±1.83), P < 0.05] and lower expression of Nogo-A [(28.88±2.64) vs. (32.50±1.60) and (23.87±2.36) vs. (32.00±1.85), P < 0.05] on day 14 and 21 after reperfusion. Meanwhile, the expression of Nogo-A on day 21 was lower than that on day 14 after reperfusion [(23.87±2.36) vs. (28.88±2.64), P < 0.05] in BMMCs group. Conclusion: These findings suggested that BMMCs treatment could improve the functional recovery of neurological deficits in rats with MCAO, which was probably related to enhanced expression of GFAP and reduced Nogo-A expression and Caspase-3 activity in the ischemic brain tissues.

Exosomes are nano-sized extracellular vesicles that are secreted by cells and usually found in body fluids. Since they freely cross the blood-brain barrier, neuronal exosomes respond directly to changes in the brain's environment. Recent studies have shown that exosomes contain both amyloid-β (Aβ) and tau proteins and have a controversial role in the Alzheimer's disease (AD) process. In this study, enzyme-linked immunosorbent assay was used to detect the levels of P-S396-tau and Aβ1-42 in plasma exosomes. We found that levels of P-S396-tau and Aβ1-42 in plasma exosomes of AD patients were significantly higher compared to those in matched healthy controls. The difference between plasma exosomes of AD patients and those of matched healthy controls was determined using transmission electron microscopy and nanoparticle tracking analysis. Exosomes from AD patients were smaller and lower in quantity. These data together may provide a basis for early diagnosis of AD.

Objectives: Muscle magnetic resonance imaging (MRI) is a reliable noninvasion tool for detecting muscle abnormalities of myopathies. This study aimed to investigate the MRI features of lower limb muscles in Chinese patients with myotonic dystrophy type 1 (DM1) and to evaluate the correlation between clinical factors and muscle MRI.Methods: We retrospectively reviewed the medical records and lower limb muscle MRI in 24 Chinese DM1 patients. Muscular Impairment Rating Scale (MIRS) was used to assess the clinical muscular impairment. Modified Mercuri's scale was used to assess the degree of fatty infiltration. Spearman rank correlation test was used to analyze the relationship between fatty degeneration score with age, age of onset, disease duration, MIRS grading and creatinine kinase (CK) level.Results: Fatty infiltration was found in 22 of 24 DM1 patients and 8 patients were asymmetrically affected. The medial gastrocnemius was the most affected muscle, followed by soleus and tibialis anterior muscles in lower legs. At thigh level, the anterior compartment was usually the most affected region with the rectus femoris relatively spared. 79.2% of DM1 patients had edema in lower limb muscles. The total mean score of fatty infiltration correlated with MIRS grading, age and disease duration but did not correlate with the age of onset or CK level.Conclusion: Here, we found fatty infiltration present in most Chinese DM1 patients with a selective involvement pattern. There is a correlation between the total mean score of fatty infiltration and MIRS grading, age and disease duration.

Immunologic changes in the hematoma of patients with intracerebral hemorrhage (ICH) and the contribution of these changes to prognosis are unknown. We collected the blood samples and hematoma fluid from 35 patients with acute ICH (

The detection of biomarkers is of great significance in the diagnosis of numerous diseases, especially cancer. Herein, we developed a sensitive and universal fluorescent aptasensor strategy based on magnetic beads, DNA G-quadruplex, and exonuclease III (Exo III). In the presence of a target protein, a label-free single strand DNA (ssDNA) hybridized with the aptamer was released as a trigger DNA due to specific recognition between the aptamer and target. Subsequently, ssDNA initiates the Exo III-aided recycling to amplify the fluorescence signal, which was caused by N-methylmesoporphyrin IX (NMM) insertion into the G-quadruplex structure. This proposed strategy combines the excellent specificity between the aptamer and target, high sensitivity of the fluorescence signal by G-quadruplex and Exo III-aided recycling amplification. We selected (50–1200 nmol/L) MUC1, a common tumor biomarker, as the proof-of-concept target to test the specificity of our aptasensor. Results reveal that the sensor sensitively and selectively detected the target protein with limits of detection (LODs) of 3.68 and 12.83 nmol/L in buffer solution and 10% serum system, respectively. The strategy can be easily applied to other targets by simply substituting corresponding aptamers and has great potential in the diagnosis and monitoring of several diseases.

Hydrogen sulfide (H2S), a well-known signaling molecule, exerts significant regulatory effects on the cardiovascular and nervous systems. Therefore, monitoring the metabolism of H2S offers a potential mechanism to detect various diseases. In addition, biotin is significantly used as a targeting group to detect cancer cells exclusively. In this work, a biotin-guided benzoxadizole-based fluorescent probe, NP-biotin, was developed for H2S detection and evaluated in normal liver cell (LO2) and liver cancer cell (HepG2) lines. Results reveal that NP-biotin can detect cellular H2S with high sensitivity and selectivity. Moreover, NP-biotin has been confirmed to possess the ability to target cancer cells under the guidance of the biotin group.

Background: Sufficient understanding of the systemic inflammatory response after stroke will make the therapeutic strategy targeting inflammation more feasible. Here, we aimed to identify the globally alterations of circulating cytokines in super-acute ischemic stroke (AIS). Methods: A broad panel of 65 cytokines was measured in the plasma of twenty-eight AIS patients within 6 hours after stroke onset ( n =28), cerebral hemorrhagic patients ( n =28) and healthy controls ( n =18). The diagnostic power of the candidate cytokines and their relationship with the number of lymphocytes and neutrophils were analyzed by receiver operating characteristic (ROC) and spearman rank correlation respectively. Results: The expression level of plasma IL-1beta, IL-2, IL-2R, IL-5, IL-10, CD40L, HGF, MIP-3alpha and MMP-1 were obviously up-regulated, while IL-16 was down-regulated in AIS patients compared to healthy controls. Among them, IL-2R, IL-10, IL-16, MIP-3alpha, and MMP-1 were specially altered in AIS patients, while IL-1beta, IL-2, IL-5, CD40L and HGF were elevated simultaneously in AIS patients and hemorrhagic stroke patients. Interestingly, IL-6 and TNF-beta were found to be key cytokines among the 65 inflammatory factors to distinguish cerebral hemorrhage from ischemia. Furthermore, plasma IL-1beta, IL-16, CD40L and HGF were obviously correlated with the number of lymphocytes, and IL-1beta and IL-16 were significantly associated with the number of neutrophils in AIS patients. These results suggest that lymphocytes and neutrophils associated inflammation may play a pivotal role in AIS. Conclusions: These significantly changed inflammatory mediators could serve as biomarkers for AIS diagnosis. More importantly, except for some mutual pathological processes, AIS and hemorrhage had their own distinctive pathogenesis, and transformation of this knowledge to further research may provide novel treatment strategy for AIS.

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a typical neurodegenerative disease associated with mitochondrial dysfunction. Methylation of the D-loop region and mitochondrial DNA copy number (mtDNAcn) play a critical role in the maintenance of mitochondrial function. However, the association between D-loop region methylation, mtDNAcn and CADASIL remains unclear. Methods Overall, 162 individuals were recruited, including 66 CADASIL patients and 96 age- and sex-matched controls. After extracting genomic DNA from the peripheral white blood cells, levels of D-loop methylation and mtDNAcn were assessed using MethylTarget sequencing and real-time PCR, respectively. Results We observed increased mtDNAcn and decreased D-loop methylation levels in CADASIL patients compared to the control group, regardless of gender stratification. Besides, we found a negative correlation between D-loop methylation levels and mtDNAcn. Mediation effect analysis shows that the proportion of the association between mtDNAcn and CADASIL that is mediated by D-loop methylation is 11.6% (95% CI 5.6, 22.6). After gender stratification, the proportions of such associations that are mediated by D-loop methylation in males and females were 7.2% (95% CI 2.4, 19.8) and 22.0% (95% CI 7.4, 50.1), respectively. Conclusion Decreased methylation of the D-loop region mediates increased mtDNAcn in CADASIL, which may be caused by a compensatory mechanism of mitochondrial dysfunction in patients with CADASIL.

Toll-like receptor 9 (TLR9) can participate in the signal transduction of activated immune cells and induce myelitis and other autoimmune diseases. The effector molecule fibrin-like protein 2 (Fgl2) plays a role in regulating the body's autoimmune signaling pathway. They both have the conditions for the treatment of this disease target. The objective of this work was to investigate the effect of Fgl2 on the expression of DNA receptor TLR9 in autoimmune myelitis. 140 rats were randomly divided into a normal control group, an autoimmune myelitis group, a low-dose Fgl2 group, a middle-dose Fgl2 group, a higher-dose Fgl2 group, a high-dose Fgl2 group, and a methylprednisolone group. Different injection methods were used in each group. The changes of rat behavior and disease were recorded, and brain and spinal cord tissue slices were made for observation. The results showed that in the high dose Fgl2 group, the incidence of disease was 15 %, the nerve injury score was 1.0 ± 0.15, the body weight change was -5.8 ± 1.24 g, the number of spinal cord tissue injury was 1.82 ± 0.44, the number of TLR9 positive cells in the brain tissue was 7.53 ± 1.84, and the number of TLR9 positive cells in spinal cord tissue was 5.02 ± 1.81. These indexes were lower than those in other Fgl2 groups and significantly lower than those in autoimmune myelitis group (P 0.05). The average incubation period of the disease was 13.66 ± 0.41 days, which was significantly higher than that of the autoimmune myelitis group (P 0.05). It can be observed that TLR9 signaling pathway played an important role in the occurrence and development of autoimmune myelitis. With the increase of Fgl2 dose, the number of TLR9 positive cells decreased gradually. Fgl2 treatment can reduce the expression of inflammatory factors and the severity of dysfunction in autoimmune myelitis, inhibit the expression of TLR9, and improve the condition of autoimmune myelitis.

Bcl2-associated athanogene 3 (BAG3) gene mutations cause dilated cardiomyopathy and myofibrillar myopathy. Recently, a novel c.625C>T (p.Pro209Ser) mutation in BAG3 was reported to cause axonal Charcot-Marie-Tooth (CMT) disease in three families. Here, we describe two patients with adult-onset and moderate CMT in a Chinese family. Nerve conduction velocity studies revealed an axonal sensorimotor neuropathy, which was supported by sural nerve biopsy. Lower limb magnetic resonance imaging (MRI) revealed fatty infiltration more severe in the soleus and deep posterior compartment muscles than in the medial gastrocnemius and anterior compartment muscles. Whole exome sequencing identified the same c.625C>T (p.Pro209Ser) mutation in BAG3, which co-segregated with the CMT disease in this family. This study further enforces the association between BAG3 gene and CMT disease, indicating that BAG3 should be considered in the genetic testing for CMT. The p.Pro209Ser mutation with different ethnic origins might be another hotspot mutation of BAG3. MRI is helpful to detect accurate extent of muscle involvement.

The pathophysiological mechanism of white matter hyperintensities of cerebral small vessel disease (CSVD) includes an impaired blood-brain barrier (BBB) with increased permeability. Neuroinflammation likely contributes to the disruption of the BBB in CSVD. Therefore, understanding the molecular mechanism of how neuroinflammation causes BBB damage is essential to preventing BBB disruption in CSVD. Matrix metalloproteinase 9 (MMP-9) contributes to BBB damage in neuroinflammatory diseases. In this study, we observed that interleukin-1β (IL-1β)-induced MMP-9 secretion in pericytes increased BBB permeability to sodium fluorescein (Na-F) by damaging the disruption of VE-cadherin, occludin, claudin-5, and zonula occludin-1 (ZO-1). Melatonin reduced BBB permeability to Na-F and inhibited the disruption of the adherens and tight junction proteins. Melatonin also downregulated MMP-9 and upregulated tissue inhibitor of metalloproteinases 1 (TIMP-1) gene expression, which decreased the MMP-9/TIMP-1 ratio. In addition, nuclear translocation of NF-κB/p65 induced by IL-1β in pericytes upregulated MMP-9 expression, which was inhibited by the NF-κB inhibitor PDTC. However, the NOTCH3 inhibitor DAPT significantly inhibited NF-κB/p65 translocation to the nucleus, while melatonin in combination with DAPT significantly prevented NF-κB/p65 translocation than DAPT alone. Our results suggest that melatonin reduced MMP-9-induced permeability of the BBB. Melatonin reduced MMP-9 expression and activity, which was induced by IL-1β through the regulation of the NOTCH3/NF-κB signaling pathway in pericytes, suggesting that pericytes regulate BBB integrity and function.

Ruirui Zhang,1 Shanjun Gao,2 Shenghui Wang,3 Jiewen Zhang,1,3 Yingying Bai,3 Shuang He,3 Pan Zhao,3 Hongju Zhang1,3 1Department of Neurology, Henan Provincial People’s Hospital Affiliated to Henan University, Zhengzhou, Henan, People’s Republic of China; 2Microbiome Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Neurology, Henan Provincial People’s Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Hongju ZhangDepartment of Neurology, Henan Provincial People’s Hospital Affiliated to Henan University, Zhengzhou, Henan, People’s Republic of ChinaEmail hongjuz@sina.comPurpose: To explore the characteristics of gut microbiota and its relationship between clinical manifestations in patients with type 1 narcolepsy (NT1).Patients and Methods: Scale and polysomnography were performed in 20 NT1 patients and 16 healthy controls (HC group) to evaluate the clinical characteristics of NT1. Illumina sequencing was performed on bacterial 16S ribosomal RNA gene using V3-V4 regions to compare the fecal microbiota in all subjects. Associations between clinical characteristics and gut microbiota were analyzed using partial correlation analysis.Results: Compared with the HC group, the NT1 group had a significantly higher ESS score, longer total sleep time, increased wakefulness, decreased sleep efficiency, disturbance of sleep structure, shorter mean sleep latency, and increased sleep-onset REM periods (all P < 0.05). No differences in alpha and beta diversity were observed between the two groups. In contrast, there were significant differences at the level of class, order, family, and genus (all P < 0.05). LEfSe analysis showed that the relative abundance of Klebsiella in the NT1 group was higher than that in the HC group (P < 0.05), while the relative abundance of Blautia, Barnesiellaceae, Barnesiella, Phocea, Lactococcus, Coriobacteriia, Coriobacteriales, Ruminiclostridium_5, and Bilophila were lower (all P < 0.05). Partial correlation analysis revealed that partial differential bacteria in the NT1 group were correlated with total sleep time, sleep efficiency, stage 1 sleep, arousal index, and sleep latency (all P < 0.05).Conclusion: Our data revealed differences in intestinal flora structure between NT1 patients and the normal population, thus providing a theoretical basis for future microecological therapy for narcolepsy. However, future larger sample size studies and different study designs are needed to further clarify the possible pathogenesis and potential causality of intestinal flora in NT1 patients and explore the new treatment strategies.Keywords: type 1 narcolepsy, gut microbiota, 16SrRNA, high throughput sequencing

Objective Hereditary spastic paraplegia (HSP) due to ERLIN2 gene mutations was designated as spastic paraplegia 18 (SPG18). To date, SPG18 families/cases are still rarely reported. All early reported cases shared the autosomal recessive (AR) inheritance pattern. Over the past 3 years, autosomal dominant (AD) or sporadic SPG18 cases had been continuously reported. Here, we reported the clinical and genetic features of the first autosomal dominant SPG18 pedigree in Chinese. Methods We conducted detailed medical history inquiry, neurological examinations of the proband and his family members, and charted the family tree. The proband underwent brain and cervical magnetic resonance imaging (MRI), electromyography (EMG), and whole exome sequencing. Sanger sequencing was performed to verify the genetic variation in the proband and some family members. A literature review of all reported SPG18 families/cases was carried out to summarize the clinical‐genetic characteristics of SPG18 under different inheritance patterns. Results Four patients were clinically diagnosed as chronic spastic paraplegia in three consecutive generations with the autosomal dominant inheritance model. All the patients presented juvenile‐adolescent onset and gradually worsening pure HSP phenotype. Clinical phenotypes were consistent within the family. Whole exome sequencing in the proband identified a previously reported heterozygous c.502G > A (p.V168M) mutation in exon 8 of ERLIN2 gene. This mutation was cosegregated with the phenotype in the family and was classified as likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines. To date, eight AR‐SPG18 families, five AD‐SPG18 families, and three sporadic cases had been reported. Clinical phenotype of AD‐SPG18 was juvenile‐adolescent onset pure HSP, while the phenotype of AR‐SPG18 was mostly complicated HSP with earlier onset and more severe conditions. In rare cases, the initial spastic paraplegia could evolve to rapidly progressive amyotrophic lateral sclerosis (ALS). Conclusions We reported the first autosomal dominant SPG18 pedigree in Chinese Han population, which added more pathogenic evidence for V168M mutation. As more SPG18 cases reported, the essentials of SPG18 need to be updated in clinical practice. Special attentions should be given in gene test for upper motor neuron disorders in case of missing heterozygous mutations in ERLIN2., we reported the first autosomal dominant SPG18 pedigree in Chinese Han population, which added more pathogenic evidence for V168M mutation. The clinical phenotypes of SPG18 are expanded and are highly heterogeneous under different inheritance patterns. As more cases reported, the essentials of SPG18 need to be updated in clinical practice and genetic testing. Special attentions should be given in genetic testing of upper motor neuron disorders in case of missing heterozygous mutations in ERLIN2.

We combine earthquake spectra from multiple studies to investigate whether the increase in stress drop with depth often observed in the crust is real, or an artifact of decreasing attenuation (incr...

Osimertinib has demonstrated promising efficacy against leptomeningeal metastasis (LM) associated with T790M-positive non-small-cell lung cancer (NSCLC). However, the effect of cerebrospinal fluid's (CSF's) epidermal growth factor receptor (EGFR) T790M mutation on osimertinib efficacy remains unclear.Seventy-eight patients were studied with EGFR-mutated NSCLC and LM. Case data were collected and EGFR mutation status of circulating cell-free DNA from paired CSF, and plasma of 23 patients with LM was detected using droplet digital PCR. The median overall survival (mOS) was 8.08 months (95% CI: 6.07–10.09) in the study. Forty-four osimertinib-treated patients had an improved mOS of 13.15 (95% CI: 5.74–20.57) and a median progression-free survival (PFS) of 9.50 months (95% CI: 6.77–12.23) when compared with patients treated with first- or second-generation EGFR-TKI (mOS = 3.00 months (95% CI: 1.32–4.68) and median PFS = 1.50 months (95% CI: 0.00–3.14)). In the osimertinib group, mOS values for CSF with and without T790M mutation were 22.15 months (95% CI: 9.44–34.87) and 13.39 months (95% CI: 7.01–19.76), respectively, with no statistical differences. Regardless of the CSF T790M mutation status, osimertinib demonstrated significant efficacy against LM associated with NSCLC.

Understanding users’ safety perception of the credibility of web-based information has become increasingly important in the context of new retailing. This study extends the existing literature by exploring the factors influencing information credibility in the context of new retailing. Based on the technology acceptance model and the rational behavior theory, a theoretical model for the assessment of information credibility in new retailing was developed. We analyzed the factors influencing users’ safety preference toward information communication procedures and information credibility in new retailing based on two aspects: perceived information quality and user judgment motivation. The reliability and validity of the model measure were analyzed, and structural equation modeling was used to test the model hypotheses. The following results were obtained: (1) Authenticity, accuracy, and practicability positively affected the perceived information quality of new retailing information; (2) User judgment motivation had a positive impact on information users’ safety preference and information credibility; (3) Users’ safety preference positively affected information credibility; (4) Information acquisition, social interaction, and self-identity positively affected the perceived credibility of new retailing information.

Background: The rate of occurrence of Alzheimer’s disease is increasing around the world. However, there is still no significant breakthrough in the study of its etiology and pathogenesis. Objective: To screen Alzheimer's disease pathogenic genes, which may be conducive to the elucidation of the pathogenic mechanisms of Alzheimer's disease And predict the pathogenicity by various computer software. Method: Clinical and neuroimaging examination, Whole Exome Sequencing, and Sanger sequencing were performed in the proband. Mutation sites were verified in 158 subjects. Results: We reported a proband carrying a probably novel pathogenic mutation, which clinically manifests as progressive memory loss, visual-spatial disorders, apraxia, psychobehavioral disorders, and temperamental and personality changes. Whole Exome Sequencing detected a novel missense mutation at codon 222 (Q222L), which is a heterozygous A to T point mutation at position 665 (c.665A>T) in exon 5 of the presenilin 1 leading to a glutamine-to-leucine substitution. The mutation was also identified by Sanger sequencing in one family member; nevertheless, it was not detected in the other 7 unaffected family members, 50 sporadic Alzheimer's disease patients and 100 control subjects. Conclusion: A novel mutation in exon 5 of the presenilin 1 gene (Gln222Leu) in a Chinese family with early-onset Alzheimer’s disease has been reported, besides， it was predicted that the missense mutation was probably a novel pathogenic mutation that was reported for the first time in a Chinese family with early-onset Alzheimer’s disease.

BACKGROUND This study aimed to identify NOTCH3 mutations and describe the genetic and clinical features and magnetic resonance imaging results in 11 unrelated patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from Henan province in China. MATERIAL AND METHODS NOTCH3 was directly sequenced in 11 unrelated patients of Chinese descent. The clinical presentations and magnetic resonance imaging features were retrospectively analyzed in the 11 index patients with a definite diagnosis. RESULTS Seven different mutations were identified in 11 unrelated patients, including 4 novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) in China and 3 reported mutations (p.C117R, p.R578C, and p.R607C). Four novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) were predicted to be probably pathogenic using an online pathogenicity prediction program through comprehensive analysis. Clinical presentations in symptomatic patients included stroke, cognitive decline, psychiatric disturbances, and migraine. Multiple lacunars infarcts and leukoaraiosis were detected on MRI in most symptomatic patients, while white-matter lesions were identified in the temporal pole or the external capsule in all affected patients. CONCLUSIONS The mutation spectrum of CADASIL patients from Henan province in China displayed some differences from that of those reported previously. DNA sequencing was used to diagnose all 11 patients as having CADASIL, and we found 4 novel mutations. The present results further contribute to the enrichment of NOTCH3 mutation databases.

Water trading is an effective method for solving regional water shortage problems and addressing the uneven spatiotemporal distribution of water resources. Therefore, taking the Middle Route of China's South-to-North Water Diversion Project (MR-SNWDP) as the research object, we present a study on a feasible water trading scheme in the water-receiving area of Henan Province. First, the tradable water of each calculation unit in the water-receiving area was calculated by analyzing the water-saving potential of different industries. Second, a multi-objective optimization model for trading water between different regions was developed, taking the largest social and economic benefits of the water-receiving area as the objective function. Finally, non-dominated sorting genetic algorithms were used to solve this optimization model, and an optimal scheme for water trading was proposed. The simulated results of the optimal scheme indicate that the total water shortage of the water-receiving areas will decrease by 650.69 million m3, and there will be a surplus of 14.98 million m3 of water, and the gross national product will increase by RMB 130.5 billion at a rate of 5.2%. This demonstrates that the water-receiving areas of Henan Province can effectively alleviate local water shortages by trading water without increasing external water supplies.

Objective: To investigate the predictive value of transcranial Doppler (TCD) ultrasound for cerebral small vessel disease in elderly patients. Methods: Transcranial Doppler ultrasound and magnetic resonance imaging (MRI) were performed on 184 elderly patients with cerebral small vessel disease. The relationship of clinical characteristics and TCD ultrasound parameters with severe white matter lesions (WMLs) in MRI were investigated by univariate analysis and multivariate analysis. Results: The univariate analysis showed that age, left middle cerebral artery (MCA) mean flow velocity, right MCA mean flow velocity and mean MCA pulsatility index were significantly correlated with severe WMLs (p < 0.05). The multivariate logistic regression analysis showed that only age (odds ratio: 1.21; 95%CI: 1.10–1.36; p < 0.01) and MCA pulsatility index (dominance ratio: 1.13; 95%CI: 1.06–1.80; p = 0.02) were significantly correlated with severe WMLs. The analysis of TCD ultrasound parameters showed that when the cut-off for MCA pulsatility index was 1.04, it could identify severe WMLs. The area under the curve was 0.70 (95%CI: 0.60–0.80). The sensitivity and specificity were 63.0% and 72.0%, respectively. The positive and negative predictive values were 35.4% and 86.6%, respectively. Conclusion: The MCA pulsatility index in TCD ultrasound is significantly correlated with severe WMLs; and TCD ultrasound can guide selective MRI for the detection of WMLs. RESUMO Objetivo: Investigar o valor preditivo do ultrassom de Doppler transcraniano (TCD) para doença de pequenos vasos (SVD) em pacientes idosos. Métodos: ultrassonografia de TCD e ressonância magnética (RM) foram realizadas em 184 idosos portadores de SVD cerebral. As relações das características clínicas e os parâmetros ultrassonográficos do TCD com lesão grave de substância branca (WML) no desempenho da RM foram investigados por análise univariada e análise multivariada. Resultados: A análise univariada mostrou que, a idade, a velocidade média de fluxo (MFV) da artéria média cerebral (MCA) esquerda, a MFV da MCA direita e o índice de pulsatilidade (PI) médio estiveram significativamente relacionados à WML grave (P

A dicyanoisophorone-based near-infrared fluorescent probe (NIR-NP) was successfully designed for hydrogen sulfide (H2S) detection. 7-Nitro-1,2,3-benzoxadiazole (NBD) amine, an electron-withdrawing group, was applied to quench the fluorescence of dicyanoisophorone-based fluorescent dyes and could be removed by H2S-specific thiolysis of an NBD amine bond, leading to a significant fluorescence turn-on response. The probe could quantitatively detect H2S with a lower detection limit (0.03 μM) in vitro and in living cells. The probe with a large Stokes shift (186 nm) showed a high selectivity to H2S in the presence of other biothiols, including glutathione, homocysteine, and cysteine. Moreover, the probe was successfully applied to image endogenous H2S in different tumor cells and in liver tissues. The excellent properties of the probe and its applications in cell and tissue imaging indicated its potential for further exploration and application of H2S in the pathophysiology of cancers and even in the diagnosis of H2S-related diseases.

Growing evidence indicates that circular RNA (circRNA) plays an important role in the regulation of tumor biological behaviors. In this study, we aimed to explore the role of a novel circRNA, circ_0034642, in glioma. qRT-PCR was conducted to evaluate the levels of circ_0034642 in glioma tissues and cells. In addition, the clinical severity and prognostic role of circ_0034642 were illustrated. Functionally, loss and gain-of function assays were performed by CCK-8, colony-forming, flow cytometric and transwell experiments in glioma cells. Moreover, luciferase reporter assay was used to detect the mechanism of circ_0034642. Circ_0034642 was upregulated in glioma tissues and cell lines. Overexpressed circ_0034642 was correlated with adverse phenotypes in the patients with glioma. In addition, circ_0034642 could be regarded as a prognostic predictor for glioma patients. Moreover, circ_0034642 could promote cell proliferation, migratory and invasive capacities and inhibit cell apoptosis. For the mechanism investigation, circ_0034642 was proved to be a sponge of miR-1205, and miR-1205 could regulate BATF3 expression via targeting 3'UTR of BATF3. Rescue assays also illustrated that the oncogenic function of circ_0034642 is partly attributed to its modulation on miR-1205/BATF3 axis. Collectively, circ_0034642/miR-1205/BATF3 pathway may play an important role in glioma.

With recent availability of COVID-19 vaccine, post-vaccination neurological complications had been occasionally reported. Here, we reported for the first time a case of neuromyelitis optica spectrum disorder (NMOSD) that developed after the first dose of inactivated virus vaccine for COVID-19. The patient developed mild fever, vomiting, diarrhea, and cough after receiving the first dose of inactivated virus vaccine. Two months later, she experienced dizziness and unsteady walking. MRI scanning of the brain revealed lesions in area postrema and bilateral hypothalamus, typical for NMOSD. Serum antibodies for AQP4, ANA, SSA, SSB, Ro-52, and p-ANCA were positive. The patient was diagnosed as AQP4-positive NMOSD with coexisting systemic autoimmunity. After treatment with methylprednisolone (500 mg for 5 days), symptoms were greatly relieved. As NMOSD is seriously harmful and curative, it is important to be aware of the NMOSD symptoms after vaccination. Cautions should be given for those with preexisting systemic autoimmune abnormalities in vaccination for COVID-19.

Background Chronic cerebral hypoperfusion (CCH) is the leading cause of cerebral small vessel disease (CSVD). CCH is strongly associated with blood–brain barrier (BBB) dysfunction and white matter lesions (WMLs) in CSVD. However, the effects of CCH on BBB integrity and components and the cellular and molecular mechanisms underlying the effects of BBB dysfunction remain elusive. Whether maintaining BBB integrity can reverse CCH-induced brain damage has also not been explored. Methods In this study, we established a rat model of CSVD via permanent bilateral common carotid artery occlusion (2VO) to mimic the chronic hypoperfusive state of CSVD. The progression of BBB dysfunction and components of the BBB were assessed using immunostaining, Western blotting, transmission electron microscopy (TEM) and RNA sequencing. We also observed the protective role of imatinib, a tyrosine kinase inhibitor, on BBB integrity and neuroprotective function following CCH. The data were analyzed using one-way or two-way ANOVA. Results We noted transient yet severe breakdown of the BBB in the corpus callosum (CC) following CCH. The BBB was severely impaired as early as 1 day postoperation and most severely impaired 3 days postoperation. BBB breakdown preceded neuroinflammatory responses and the formation of WMLs. Moreover, pericyte loss was associated with BBB impairment, and the accumulation of serum protein was mediated by increased endothelial transcytosis in the CC. RNA sequencing also revealed increased transcytosis genes expression. BBB dysfunction led to brain damage through regulation of TGF-β/Smad2 signaling. Furthermore, imatinib treatment ameliorated serum protein leakage, oligodendrocyte progenitor cell (OPC) activation, endothelial transcytosis, microglial activation, and aberrant TGF-β/Smad2 signaling activation. Conclusions Our results indicate that reduced pericyte coverage leads to increased BBB permeability via endothelial transcytosis. Imatinib executes a protective role on the BBB integrity via inhibition of endothelial transcytosis. Maintenance of BBB integrity ameliorates brain damage through regulation of TGF-β/Smad2 signaling following CCH; therefore, reversal of BBB dysfunction may be a promising strategy for CSVD treatment.