Brain, behavior, & immunity - health最新文献

{"title":"Proinflammatory transcriptomic and kinomic alterations in astrocytes derived from patients with familial Alzheimer's disease","authors":"Benjamin Siciliano ,&nbsp;Nicholas D. Henkel ,&nbsp;William G. Ryan V ,&nbsp;Ali Sajid Imami ,&nbsp;John M. Vergis ,&nbsp;Chongchong Xu ,&nbsp;Taylen O. Arvay ,&nbsp;Smita Sahay ,&nbsp;Priyanka Pulvender ,&nbsp;Abdul-rizaq Hamoud ,&nbsp;Chadwick Hales ,&nbsp;Robert E. McCullumsmith ,&nbsp;Zhexing Wen","doi":"10.1016/j.bbih.2025.101044","DOIUrl":"10.1016/j.bbih.2025.101044","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by profound neuronal and cognitive decline, with increasing evidence implicating astrocyte dysfunction in disease pathology. While traditional therapeutic approaches have primarily targeted neurons, the crucial role of astrocytes in metabolism, neurotransmission, amyloid-beta clearance, and neuroinflammation underscores their potential as therapeutic targets. In this study, we employed a multiomic integrative analysis combining transcriptomic and kinomic profiling of human induced pluripotent stem cell (hiPSC)-derived astrocytes from patients with familial AD (fAD) compared to healthy controls (HCs). Our transcriptomic analysis identified 1249 significantly differentially expressed genes, highlighting a pronounced upregulation of inflammatory genes (<em>SERPINA3</em>, <em>IL6R</em>, <em>IL1RAP</em>, <em>TNFRSF11A</em>) and a concomitant downregulation of genes essential for synaptic support and ion channel function (<em>STMN2</em>, <em>NMNAT2</em>, <em>SCN2A</em>, <em>GRIN1</em>). Kinomic profiling revealed dysregulated kinase activities within DYRK, GSK, and MAPK families, further implicating altered kinase signaling pathways in astrocyte dysfunction. Integration of these datasets pinpointed critical molecular hubs, notably within the PI3K signaling and inflammatory pathways, highlighting targets such as <em>JAK2</em>, <em>STAT3</em>, and <em>AKT1</em> as potential modulators of disease progression. Furthermore, leveraging the Library of Integrated Network-Based Cellular Signatures (LINCS) platform, we identified chemical perturbagens, including fluticasone propionate and Akt inhibitors, capable of reversing the transcriptomic signatures associated with fAD astrocytes. This integrative multiomic approach not only enhances our understanding of astrocyte-specific molecular mechanisms in AD but also provides novel targets for therapeutic intervention aimed at mitigating astrocyte-driven neurodegeneration.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101044"},"PeriodicalIF":3.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EBI2-oxysterol signalling regulates VE-cadherin expression and multiple sclerosis CD4+ T cell attachment to a human tri-cell spheroid blood-brain barrier model","authors":"Fionä Caratis ,&nbsp;Inez Mruk ,&nbsp;Klaudia Konieczna-Wolska ,&nbsp;Bartłomiej Rojek ,&nbsp;Marek Hałas ,&nbsp;Paulina Czaplewska ,&nbsp;Bartosz Karaszewski ,&nbsp;Tomomi Furihata ,&nbsp;Aleksandra Rutkowska","doi":"10.1016/j.bbih.2025.101045","DOIUrl":"10.1016/j.bbih.2025.101045","url":null,"abstract":"<div><div>Changes in the function of the blood-brain barrier (BBB) are one of the hallmarks of multiple sclerosis (MS) and are observed at very early stages of the disease. Several disease-modifying therapies for MS regulate tight junction and adherence junction proteins in the BBB thus limiting the entry of peripheral immune cells into the central nervous system (CNS). The Epstein-Barr virus-induced gene 2 (EBI2) was shown to drive immune cell migration towards high concentration of its endogenous ligand, oxysterol 7α,25OHC, which concentrations increase during inflammation in the CNS. Here, the data showed upregulated transcripts of <em>EBI2</em> and <em>CH25H</em>, the first enzyme in 7α, 25OHC synthesis pathway, in MS brain lesions. <em>In vitro</em>, cerebrospinal fluid (CSF) from patients with MS downregulated <em>HSD3B7</em>, the 7α, 25OHC degrading enzyme, and <em>VE-cadherin</em> levels in the tri-cell human BBB spheroid model. Importantly, EBI2 signalling mediated the attachment of MS patient-derived CD4⁺ T cells to the BBB spheroids. The data raises the possibility that elevated oxysterol levels in an inflamed brain might trigger a downregulation of VE-cadherin in endothelial cells, potentially easing the CNS infiltration of EBI2-expressing immune cells. This process can be modulated through the use of EBI2 ligands, suggesting a potential pathway for therapeutic intervention.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101045"},"PeriodicalIF":3.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of neurodevelopmental disorders in the offspring of mothers with a history of endometriosis in Taiwanese women","authors":"Pei-Yin Yang ,&nbsp;Ching-Ming Wang ,&nbsp;Pei-Lun Liao ,&nbsp;Jing-Yang Huang ,&nbsp;Keng-Wei Liang ,&nbsp;Yu-Hsuan Lin ,&nbsp;Shun-Fa Yang ,&nbsp;Po-Hui Wang","doi":"10.1016/j.bbih.2025.101038","DOIUrl":"10.1016/j.bbih.2025.101038","url":null,"abstract":"<div><div>Several neurodevelopmental disorders have been linked to early life immune activation and inflammation, including developmental delay, cerebral palsy, intellectual disabilities, and other neurodevelopmental and psychiatric disorders. Certain inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, secreted by endometriosis cells cause chronic pelvic inflammation and pain. The aim of this study was to evaluate whether maternal endometriosis increased the risk of neurodevelopmental disorders in offspring in <u>Taiwanese women</u>. The study included eligible mother–offspring pairs with maternal endometriosis (the case cohort) and mother–offspring pairs without maternal endometriosis (the comparison cohort) matched for maternal age at delivery, infant sex, and delivery date, both with offspring born during 2009–2016 and followed till 2019, from the Taiwan Maternal and Child Health Database. The incidence rates and crude hazard ratios (HRs) of development delay and cerebral palsy in the offspring delivered by mothers with endometriosis were higher than those in the offspring delivered by mothers without endometriosis (developmental delay: incidence 1.51 vs. 1.30 per 1000 person-months, crude HR = 1.16; cerebral palsy: incidence 0.04 vs. 0.03 per 1000 person-months, HR = 1.38). In model 1, the adjusted HRs of development delay and cerebral palsy in the offspring of mothers with endometriosis were 1.16 (95 % confidence interval [CI] = 1.11–1.22, <em>P</em> &lt; 0.0001) and 1.39 (95 % CI = 1.04–1.85, <em>P</em> = 0.0256). In model 2, these were 1.11 (95 % CI = 1.06–1.17) and 1.01 (95 % CI = 0.76–1.36), respectively. However, the HRs of intellectual disabilities and other neurodevelopmental and psychiatric disorders were not significantly different between the offspring of mothers with and without endometriosis. In conclusion, maternal endometriosis may increase the risks of cerebral palsy and specifically developmental delay in offspring.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101038"},"PeriodicalIF":3.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perinatal depressive and anxiety symptoms are associated with gut microbiota in pregnant women with overweight and obesity","authors":"Janina Hieta ,&nbsp;Chouaib Benchraka ,&nbsp;Katariina Pärnänen ,&nbsp;Noora Houttu ,&nbsp;Kati Mokkala ,&nbsp;Mrunalini Lotankar ,&nbsp;Eeva-Leena Kataja ,&nbsp;Leo Lahti ,&nbsp;Kirsi Laitinen","doi":"10.1016/j.bbih.2025.101042","DOIUrl":"10.1016/j.bbih.2025.101042","url":null,"abstract":"<div><div>The associations of gut microbiota with depressive and anxiety symptoms have been investigated mainly in non-pregnant humans, and currently there is a significant gap in research on pregnant women, especially those who are living with overweight and thus at a higher risk for experiencing perinatal mental health problems. In this study, we used shotgun metagenomic sequencing to analyze the gut microbiota of pregnant women with overweight and obesity, both in early and late pregnancy. We compared gut microbial diversity, composition, and function across groups with different trajectories of depressive (n=419) and anxiety (n=408) symptoms. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS), and anxiety symptoms were evaluated with the Symptom Checklist 90 (SCL-90, anxiety subscale) at five time points spanning from early pregnancy to one year postpartum. Latent growth mixture modeling (LGMM) was used to model symptom trajectories from early pregnancy until one year postpartum and further symptom sum scores at five time points cross-sectionally. We observed differences in several bacterial species abundances between the trajectory groups and in cross-sectional analyses, including higher abundance of <em>Hungatella hathewayi</em> in the Moderate and increasing depressive symptoms group (FDR&lt;0.25), and <em>Bacteroides clarus</em> in the High and decreasing depressive symptoms group (FDR&lt;0.25) and in women experiencing clinically significant postpartum anxiety symptoms (FDR&lt;0.05). No differences were found regarding the gut microbiota diversity (α or β) or function. The results suggest that maternal gut microbiota, particularly the increased abundance of possible pro-inflammatory species, could be one of the factors affecting perinatal distress.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101042"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated neural coding in the vagus nerve during long sepsis","authors":"Joshua J. Strohl ,&nbsp;Tomás S. Huerta ,&nbsp;Sergio Robbiati ,&nbsp;Patricio T. Huerta","doi":"10.1016/j.bbih.2025.101043","DOIUrl":"10.1016/j.bbih.2025.101043","url":null,"abstract":"<div><div>Sepsis is a life-threatening condition characterized by organ dysfunction resulting from the body's unbalanced and excessive response to an infection. ‘Long sepsis’ (LS) is an emerging concept referring to persistent sequelae experienced by long-term sepsis survivors, which include cognitive impairment, immune dysfunction, high cardiovascular risk, fatigue, and depression. Here, we investigated the role of the vagus nerve, a key component of the inflammatory reflex, in a mouse model of LS. Six weeks after cecal ligation and puncture (CLP) or sham surgery, we performed electrophysiological recordings from the cervical vagus nerve in anesthetized male mice. We found that LS mice exhibited significantly higher baseline vagal activity compared to controls, with elevated firing rates during both respiratory bursts and inter-burst intervals. Control mice showed clear increases in vagal activity following systemic administration of pro-inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-1β (IL-1β), but LS mice displayed markedly dysregulated responses. LS mice showed altered firing dynamics, with many vagal units decreasing rather than increasing their activity after cytokine stimulation. Using a naïve Bayes decoder, we demonstrated that LS disrupted the neural code in the vagus nerve, significantly altering its activity pattern in response to cytokine signals. These results suggest that LS fundamentally alters vagus nerve function, with elevated baseline activity and diminished responsiveness to inflammatory signals. This neurophysiological dysregulation may contribute to the persistent multi-organ dysfunctions observed in long sepsis survivors, suggesting a potential role for vagal signaling in sepsis outcomes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101043"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parasympathetic nervous activity and CTRA gene expression among healthy young adults in Japan","authors":"Yoshino Murakami ,&nbsp;Takeshi Hashimoto ,&nbsp;Steve Cole","doi":"10.1016/j.bbih.2025.101040","DOIUrl":"10.1016/j.bbih.2025.101040","url":null,"abstract":"<div><div>Previous research suggests that parasympathetic nervous system (PNS) activity may inhibit the leukocyte Conserved Transcriptional Response to Adversity (CTRA) which has been observed in individuals exposed to prolonged stressors like loneliness, social isolation, and bereavement. Previous PNS-CTRA studies have focused on Western populations, raising questions about the generalizability of these findings across different cultural and ethnic backgrounds. This study examined the relationship between PNS activity (as indexed by heart rate variability; HRV) and CTRA gene expression in young, healthy adults in Japan (n = 26; Mean age = 26; 34.6 % female). In analyses that controlled for demographic and behavioral covariates (including age, sex, ethnicity, smoking, alcohol, and BMI), results showed a significant inverse relationship between HRV and CTRA gene expression (i.e., lower expression of pro-inflammatory genes and elevated expression of Type I interferon response genes). Convergent validation analyses of genome-wide transcription factor activity linked HRV to up-regulation of Interferon Response Factors and down-regulation of NF-κB. These results parallel previous findings from Western samples, confirming that PNS neuro-immune regulation generalizes to an population based in Japan, as part of broader East Asian region and identifying HRV as a useful index for optimizing immune health in diverse populations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101040"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibody profiling of autism spectrum disorder patients with monoamine oxidase a deficiency","authors":"Guan-Da Syu ,&nbsp;Yawei Cheng ,&nbsp;Kevin Chen ,&nbsp;Chih-Yung Yang ,&nbsp;F.X. Reymond Sutandy ,&nbsp;Chia-Chien Liu ,&nbsp;Chien-Sheng Chen ,&nbsp;Jean C. Shih","doi":"10.1016/j.bbih.2025.101039","DOIUrl":"10.1016/j.bbih.2025.101039","url":null,"abstract":"<div><div>Monoamine oxidase A (MAO A) is a key enzyme for serotonin metabolism. Knockout MAO A in mice results in elevated serotonin, altered serum autoantibodies, and autistic-like behavior. There is a subset of patients with autism spectrum disorder (ASD) who exhibit hyperserotonemia. The link between the MAO A, hyperserotonemia, immunity, and ASD is still unknown. To address this question, we harness the high-density human proteome microarray to profile the serum autoantibodies in ASD patients with or without MAO A deficiency. We recruited 25 subjects, including 20 ASD patients, from National Yang Ming Chiao Tung University Hospital and determined their plasma serotonin levels, screened for MAO A gene mutations and identified one patient with a C374 G mutation, which abolished MAO A activity and showed the highest serotonin level (hsASD; 518.42 ng/ml) and severe ASD symptoms. In another family with twin brothers, one was diagnosed with mild ASD and exhibited an increased serotonin level (isASD; 31.48 ng/ml), while the other twin was a healthy control. These three subjects were used for serum autoantibody profiling using high-density human proteome microarrays. Comparing serum antibodies from hsASD with healthy control, we identified 354 up-regulated and 398 down-regulated autoantibodies in hsASD. By comparing isASD with healthy controls, we reported 235 up-regulated and 279 down-regulated autoantibodies in isASD. Interestingly, the up-regulated autoantibodies for hsASD were enriched in the brain region and exhibited distinct features from that of isASD. This study indicates that MAO A deficiency and serotonin levels significantly impact the immunological changes in ASD patients, which may shed some light on pathological mechanisms and provide potential biomarkers for translational research in ASD.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101039"},"PeriodicalIF":3.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Where's my mom? Resilient maternal preference in post-weaning male and female mice within a multi-chamber social behavior task","authors":"Maggie M. Slamin ,&nbsp;Indra R. Bishnoi ,&nbsp;Izabella M. Bankowski,&nbsp;Haley A. Norris,&nbsp;Evan A. Bordt","doi":"10.1016/j.bbih.2025.101034","DOIUrl":"10.1016/j.bbih.2025.101034","url":null,"abstract":"<div><div>One of the earliest and most important social bonds for many mammals is the bond formed with their mother. Mothers often provide essential benefits for offspring development and survival. Growing evidence suggests that this social bond is retained even when animals gain independence, such as during the juvenile period immediately following weaning. Here, we investigated whether or not juvenile mice (postnatal day [P]26) retain the ability to recognize and prefer their mothers post-weaning. We further investigated the strength of this bond using an acute immune activator. On P26, male and female C57BL/6J mice were intraperitoneally injected with the endotoxin lipopolysaccharide (LPS) or saline control (0.5 mg/kg). Four hours later, mice were subject to a five-chamber social preference task (the AGORA) containing their biological mother, a sex- and age-matched novel mouse, a sex- and age-matched sibling, a novel object, and an empty chamber. Our findings reveal that juvenile mice exhibit a strong maternal preference, which was significantly greater than chance and higher compared to any other social or non-social stimuli. While LPS exposure reduced the time spent investigating all stimuli, juvenile maternal preference was not significantly altered by LPS exposure. These effects were especially pronounced in females, while subtle shifts towards novel exploration began to emerge in males by P26. The novel multi-chamber task employed in the present study offered a more nuanced understanding of how social bonds evolve and vary across sex. The current findings suggest that juvenile mice have a robust social preference for their mother that is resilient to early-life immune activation.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101034"},"PeriodicalIF":3.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic S100A8/A9 in patients with moderate to severe acute ischemic stroke: Exploratory analysis of inflammation and functional outcome","authors":"Christoph Vollmuth ,&nbsp;Felipe A. Montellano ,&nbsp;Cornelia Fiessler ,&nbsp;Fabian Essig ,&nbsp;Christian Hametner ,&nbsp;Alexander M. Kollikowski ,&nbsp;Vivian Vogt ,&nbsp;Mirko Pham ,&nbsp;Peter U. Heuschmann ,&nbsp;Karl Georg Haeusler ,&nbsp;Guido Stoll ,&nbsp;Hermann Neugebauer ,&nbsp;Michael K. Schuhmann","doi":"10.1016/j.bbih.2025.101041","DOIUrl":"10.1016/j.bbih.2025.101041","url":null,"abstract":"<div><h3>Introduction</h3><div>S100A8/A9, a danger-associated molecular pattern (DAMP), is released from leukocytes, mainly neutrophils, and augments inflammation and tissue damage. The role of systemic plasma levels of S100A8/A9 in stroke-related inflammation and its association with clinical outcome lacks sufficient data.</div></div><div><h3>Methods</h3><div>Prospective, monocentric, observational study including patients with moderate to severe acute ischemic anterior circulation stroke [National Institutes of Health Stroke Scale (NIHSS) score ≥6 points and/or mechanical recanalization)]. We assessed functional outcome by telephone interview 3 months (±14 days) after stroke using the 7-point modified Rankin Scale (mRS). Poor outcome was defined as mRS ≥3. Systemic plasma levels of S100A8/A9 were determined by ELISA &lt;48 h after onset of symptoms, alongside a differential blood count. Univariable and multivariable logistic regression were performed to investigate the association between systemic plasma levels of S100A8/A9 and functional outcome.</div></div><div><h3>Results</h3><div>Between June 2020 and September 2022, a total of 272 patients were enrolled [52 % female, median age 79 years (IQR: 66–84), median NIHSS score on admission 13 (IQR: 8–17), median ASPECTS 8 (IQR: 6–9)]. Of these, 220 patients (81 %) underwent mechanical recanalization, and 118 (43 %) received systemic thrombolytic therapy. There was a significant correlation between systemic plasma levels of S100A8/A9 and neutrophil counts at baseline [p &lt; 0.0001; r = 0.33 (95 % confidence interval: 0.22; 0.44)]. At 3 months, 192 of 272 (71 %) patients had poor functional outcome, who had significantly higher systemic plasma levels of S100A8/A9 at baseline [median: 525 ng/ml (IQR: 342–897)] than those with good functional outcome [397 ng/ml (IQR: 232–580); p = 0.001]. Furthermore, systemic plasma levels of S100A8/A9 at baseline were associated with poor outcome [unadjusted odds ratio (OR): 2.01 (95 %CI: 1.04–3.96)], however this association was attenuated and no longer significant when adjusting for age, sex, NIHSS Score on admission, ASPECT Score on admission and recanalization therapy (yes/no) [adjusted OR: 1.92 (95 %CI: 0.86–4.34)].</div></div><div><h3>Conclusions</h3><div>Systemic plasma levels of S100A8/A9 were associated with poor outcome in patients with moderate to severe ischemic stroke. The observed correlation with neutrophil counts at baseline might underscore an important pathophysiological link between patients’ prognosis and stroke-related inflammation.</div></div><div><h3>Study registration</h3><div>DRKS00022064.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101041"},"PeriodicalIF":3.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mediating role of Interleukin-6 in the predictive association of diabetes with Hippocampus atrophy, Amyloid, Tau, and Neurofilament pathology at pre-clinical stages of diabetes-related cognitive impairment","authors":"Asma Hallab ,&nbsp;The Health and Aging Brain Study (HABS-HD) Study Team","doi":"10.1016/j.bbih.2025.101031","DOIUrl":"10.1016/j.bbih.2025.101031","url":null,"abstract":"<div><h3>Introduction</h3><div>Type-2 diabetes (T₂DM) has been associated with higher dementia risks, but the mechanisms are still unclear, and there is increasing evidence of the role of cytokines. Interleukin-6 (IL-6) mediating effect has never been explored.</div></div><div><h3>Methods</h3><div>The study included a subset of 1927 community-dwelling participants from the Health and Aging Brain Study: Healthy Disparities (HABS-HD) cohort with complete data. Cross-sectional and longitudinal analyses were performed. Associations were studied using multivariable linear, logistic, and mediation analysis with non-parametric bootstrapping.</div></div><div><h3>Results</h3><div>T₂DM and IL-6 were associated with worse executive function, Hippocampus atrophy, lower Aß₄₂/Aß₄₀ ratio, and higher Aß₄₀, Aß₄₂, total Tau, and NfL levels. IL-6 mediated 5 % of the association of T₂DM with Aß₄₀ ([1.5 %–10 %], <em>p-</em>value&lt;2 × 10⁻¹⁶), 4 % with Aß₄₂ ([0.7 %–11 %], <em>p-</em>value = 0.014), 8 % with TMT-B ([0.2 %–35 %], <em>p-</em>value = 0.046), 11 % with total Tau ([2.5 %–40 %], <em>p-</em>value = 0.010), 5 % with NfL ([1.6 %–8 %], <em>p-</em>value&lt;2 × 10⁻¹⁶), and 12 % Hippocampus atrophy ([3 %–49 %], <em>p-</em>value = 0.004). The results, except TMT-B, were replicated in the longitudinal analysis of long-lasting T₂DM on non-previously diagnosed cognitive impairment.</div></div><div><h3>Conclusions</h3><div>The study captured a pre-clinical stage of the T₂DM-dementia association. The mediating effect of IL-6 is a novelty that has to be further explored and accounted for in risk stratification and preventive measures, particularly in ethnic minorities.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101031"},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}