Brain, behavior, & immunity - health最新文献

{"title":"Body talk: Correlates of gut-immune dysregulation phenotypes in people living with HIV who use methamphetamine","authors":"Wilson Vincent ,&nbsp;Annesa Flentje ,&nbsp;Benjamin S. Dominguez ,&nbsp;Robert H. Paul ,&nbsp;Savita Pahwa ,&nbsp;Suresh Pallikkuth ,&nbsp;Margaret Roach ,&nbsp;Dietmar Fuchs ,&nbsp;Samantha E. Dilworth ,&nbsp;Torsten B. Neilands ,&nbsp;Peter W. Hunt ,&nbsp;Gowri Sunder ,&nbsp;Cody Lentz ,&nbsp;Sydney Telaak ,&nbsp;Adam W. Carrico","doi":"10.1016/j.bbih.2025.101156","DOIUrl":"10.1016/j.bbih.2025.101156","url":null,"abstract":"<div><h3>Background</h3><div>Microbial translocation, immune activation, inflammation, and dysregulated metabolism of neurotransmitter precursors are interacting pathophysiologic processes linked to neuropsychiatric comorbidities and faster HIV disease progression. We examined correlates of distinct phenotypes of gut-immune dysregulation in people living with HIV (PWH) who use methamphetamine.</div></div><div><h3>Methods</h3><div>Participants were 122 PWH who had biochemically confirmed recent methamphetamine use, including non-injection use. Peripheral plasma markers reflected: intestinal permeability, microbial translocation, immune activation, inflammation, and dysregulated metabolism of neurotransmitter precursors. Using latent profile analysis (i.e., clustering) of these markers, we identified gut-immune phenotypes and their clinical, demographic, and stigma-related correlates.</div></div><div><h3>Results</h3><div>Three immune profiles emerged: (1) <em>low gut-immune dysregulation</em> with lower microbial translocation, macrophage activation, inflammation, and tryptophan catabolism; (2) <em>moderate gut-immune dysregulation</em> with all markers within average range; and (3) <em>high gut-immune dysregulation</em> with higher microbial translocation, immune activation, inflammation, and tryptophan catabolism. In adjusted analyses, higher viral load (one log10 copy/ml; <em>AOR</em> = 1.97, 95 % CI = 1.02–3.82), injection of methamphetamine (<em>AOR</em> = 3.60, 95 % CI = 1.23–10.50), and internalized stigma (<em>AOR</em> = 1.78, 95 % CI = 1.01–3.15) were associated with having a moderate gut-immune dysregulation profile. Additionally, higher viral load (<em>AOR</em> = 2.98, 95 % CI = 1.53–5.24) and injecting methamphetamine (<em>AOR</em> = 5.45, 95 % CI = 1.34–17.78) were associated with having a high gut-immune dysregulation profile.</div></div><div><h3>Conclusions</h3><div>Distinct patterns of microbial translocation, immune activation, inflammation, and metabolism of amino acid precursors distinguished gut-immune phenotypes of PWH reporting injection methamphetamine use and greater internalized stigma. Interventions tailored to PWH who inject methamphetamine or struggle with internalized stigma could optimize HIV-related health outcomes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101156"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712257","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":"Glial activation and increase in cerebral pro-inflammatory cytokine expression in a female animal post-COVID model","authors":"Silvia Flaj Prados ,&nbsp;Esperanza Herradón Pliego ,&nbsp;Carlos Goicoechea Garcia ,&nbsp;Eva Ma Sánchez-Robles ,&nbsp;Lars Arendt-Nielsen ,&nbsp;Cesar Fernández-de-las-Peñas ,&nbsp;Visitación López-Miranda","doi":"10.1016/j.bbih.2025.101148","DOIUrl":"10.1016/j.bbih.2025.101148","url":null,"abstract":"<div><h3>Introduction</h3><div>Many COVID-19 survivors suffer long-term multi-organ damage leading to some symptoms such as brain fog. Around 25 % of patients report persistent memory loss, concentration difficulties, or other cognitive impairments after a SARS-COV-2 infection. Animal models are crucial for studying the pathophysiology of post-acute COVID-19 sequelae (PASC).</div></div><div><h3>Objective</h3><div>To assess the presence of neuro-inflammatory and glial activation biomarkers in brain tissue after a SARS-CoV-2 infection in an animal model to better understand the pathophysiology of neurocognitive symptoms.</div></div><div><h3>Methods</h3><div>Twelve C57BL/6 female hACE2 mice infected with SARS-CoV-2 Omicron variant (BA.1.17 lineage) and eleven non-infected female mice were included. Different proteins evaluating the innate immune activation in neuro-inflammation (TLR4, MyD88, NF-κB signalling pathway), inflammatory state (interleukins IL-6, IL-18 and IL-1β), and glial neuro-inflammatory response (CD11d, Iba1, GFAP expression) were evaluated from cerebral tissue 28 days after infection.</div></div><div><h3>Results</h3><div>As compared to non-infected mice, significant higher (p = 0.014) post-COVID expression of IL-18 (suggesting an inflammatory state) and significant higher (p = 0.0473) post-COVID GFAP expression (indicating enhanced astrocytic glia activation in response to the infection) was observed in brain tissue. No significant differences in TLR4 (p = 0.512), MyD88 (p = 0.151), NF-κB p65 (p = 0.712), IL-6 (p = 0.962), IL-1β (p = 0.343), CD11d (p = 0.750), and Iba1 (p = 0.935) expressions were observed.</div></div><div><h3>Conclusions</h3><div>This study provides evidence on brain neuro-inflammation, highlighting glial activation and IL-18 overexpression after an acute SARS-CoV-2 infection. These findings improve current understanding of post-COVID neuroinflammation and could aid in the design of treatment strategies for persistent neurological sequelae, such as cognitive impairment and mental confusion.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101148"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684291","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":"Moderating effects of individual factors on the relationship between inflammation and psychophysiological states in healthy adults","authors":"Kao Yamaoka ,&nbsp;Yuri Ishii ,&nbsp;Yuri Terasawa","doi":"10.1016/j.bbih.2025.101135","DOIUrl":"10.1016/j.bbih.2025.101135","url":null,"abstract":"<div><div>Systemic inflammation affects psychological processes. Although the association between inflammation and psychophysiological state has been extensively investigated in patients with depression or inflammatory disease, how this relationship manifests in healthy individuals is not clearly known. Not all individuals exhibit distress in response to elevated inflammatory markers, suggesting the presence of psychological moderators. Elucidating the effect of elevated inflammatory markers on healthy adults would broaden the understanding of the relationship between inflammation and psychophysiological state. We investigated the moderating effect of individual factors, including emotion regulation, sleep quality, and interoceptive awareness, on the relationship between inflammatory markers and psychophysiological states in healthy adults. A total of 155 participants aged 30–59 years were assessed for inflammatory markers, individual factors, and subjective psychological and physical symptoms. Hierarchical regression and interaction models revealed that individuals with poor emotion regulation or low-quality sleep showed stronger associations between inflammatory markers and symptoms such as fatigue, somatic complaints, depression, and anxiety. Conversely, individuals with effective emotion regulation or high-quality sleep exhibited attenuated or even reversed associations, suggesting protective effects. Interoceptive awareness showed weaker and more context-dependent moderating effects. These results highlight the importance of psychological traits in modulating the effects of inflammation on mental and physical well-being in clinically healthy adults. Targeted interventions for enhancing emotion regulation and sleep quality may mitigate the psycho-physiological burden of inflammation and reduce the risk of future disease onset. The findings underscore the need for individualized psychoneuroimmunological models that incorporate trait-level moderators to explain variability in stress-related health outcomes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101135"},"PeriodicalIF":3.5,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571557","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":"IL-1b and TNF-a-driven sleep alterations: Neuroimmune mechanisms and behavioral implications","authors":"Nathan Zhang ,&nbsp;Kyungsoo Park ,&nbsp;Shinjae Chung ,&nbsp;Yeong Shin Yim","doi":"10.1016/j.bbih.2025.101139","DOIUrl":"10.1016/j.bbih.2025.101139","url":null,"abstract":"<div><div>Sleep is a fundamental physiological state essential for immune function, metabolic regulation, and recovery from illness. During infection, sleep patterns are altered in a stereotyped fashion-characterized by increased non-rapid eye movement (NREM) sleep and reduced rapid eye movement (REM) sleep. These sleep changes are not incidental consequences of illness but reflect an evolutionarily conserved neuroimmune adaptation driven by proinflammatory cytokines. In particular, interleukin 1b (IL-1b) and tumor necrosis factor-a (TNFa) modulate sleep by acting directly on central nervous system circuits, including the serotonergic system and homeostatic sleep regulation. In this review, we synthesize current knowledge on how IL-1b and TNFa interact with sleep-regulating networks to alter behavioral state transitions during immune challenge. We also explore the broader clinical relevance of cytokine-driven sleep changes across infectious, psychiatric, and neurodegenerative disorders, and highlight emerging therapeutic opportunities targeting neuroimmune pathways to restore sleep homeostasis. Understanding these interactions is essential for advancing mechanistic insight into sleep regulation and for improving clinical management of inflammation-related sleep disturbances.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101139"},"PeriodicalIF":3.5,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145521108","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":"Social stress changes gut microbiome composition in male, female, and aggressor mice","authors":"Isabel Garcia ,&nbsp;Fatmanur Kilic ,&nbsp;Chris-Ann Bryan ,&nbsp;Jose Castro-Vildosola ,&nbsp;Sai Anusha Jonnalagadda ,&nbsp;Akhila Kasturi ,&nbsp;Jacqueline Tilly ,&nbsp;Jordyn Smith ,&nbsp;Sofia Valentin ,&nbsp;Sergio Moncayo ,&nbsp;Tamara Hala ,&nbsp;Eric Klein ,&nbsp;Brian F. Corbett","doi":"10.1016/j.bbih.2025.101138","DOIUrl":"10.1016/j.bbih.2025.101138","url":null,"abstract":"<div><div>Psychological stress causes gut dysbiosis, which is associated with adverse effects on physical and mental health in humans and mice. Identifying taxa of gut bacteria changed by stress, and whether stress differentially alters their relative abundance in males and females, has important implications for stress-related disorders. We modeled individual differences in resilience or susceptibility using the chronic social defeat stress (CSDS) paradigm. Here, C57BL/6 mice are exposed to a novel retired breeder CD-1 aggressor for 10 min per day for 10 days. In this paradigm, resilient and susceptible subpopulations can be identified using the social interaction paradigm following CSDS. Fecal samples were collected immediately following Day 1 and Day 10 of CSDS. 16S ribosomal RNA sequencing was used to identify the relative abundance of 200 bacteria species. We analyzed group differences in phyla, genera, and species in resilient, susceptible, and non-stressed control male and female C57/BL/6 intruders along with CD-1 aggressors. Stress reduced microbiome diversity and caused gut dysbiosis in all groups, including aggressors. These changes were not observed in non-stressed mice. CSDS altered the relative abundance of every gut bacteria phylum. CSDS reduced genera in the Firmicutes phylum whereas sex altered fewer genera. The relative abundance of an uncultured <em>Ruminococcus</em> species on Day 1 predicted social avoidance following CSDS, with a stronger correlation in stressed females compared to males. Together, our findings demonstrate that CSDS changes gut microbiome composition in male and female mice.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101138"},"PeriodicalIF":3.5,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520733","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":"Relationship between body mass index, gray matter volume and peripheral inflammation in patients with post-COVID condition","authors":"Luise Victoria Claaß ,&nbsp;Franziska Schick ,&nbsp;Tonia Rocktäschel ,&nbsp;Alejandra P. Garza ,&nbsp;Christian Gaser ,&nbsp;Philipp A. Reuken ,&nbsp;Andreas Stallmach ,&nbsp;Kathrin Finke ,&nbsp;Sharmili Edwin Thanarajah ,&nbsp;Martin Walter ,&nbsp;Ildiko Rita Dunay ,&nbsp;Bianca Besteher ,&nbsp;Nils Opel","doi":"10.1016/j.bbih.2025.101137","DOIUrl":"10.1016/j.bbih.2025.101137","url":null,"abstract":"<div><h3>Background</h3><div>Obesity, a condition associated with low-grade peripheral inflammation, is an independent risk factor for severe COVID-19 and has been linked to structural brain alterations. Given that post-COVID condition (PCC) is also associated with structural brain abnormalities and lingering immunological alterations, this study aimed to assess whether obesity contributes to these neural and immunological differences in PCC patients.</div></div><div><h3>Methods</h3><div>We investigated a previously established cohort of PCC patients (n = 61), recruited between April 2021 and June 2022. Whole-brain comparison of gray matter volume (GMV) was conducted by voxel-based morphometry (VBM). Obesity, as measured by body mass index (BMI), as well as age, sex, and total intracranial volume (TIV), were included as regressors in a linear model. Signature immunological markers were quantified in 50 participants using a LEGENDplex™ multiplex bead-based assay.</div></div><div><h3>Results</h3><div>A significant negative association was found between BMI and GMV in the right thalamus (p(FWE) = 0.039, k = 209, TFCE = 1037.97, x = 18, y = −21, z = 8). Moreover, BMI and thalamic GMV were significantly associated with immunological markers in PCC. Specifically, BMI was positively associated with Interleukin-6 (p = 0.021) and negatively with Interleukin-7 (p = 0.021), while GMV showed positive associations with Interleukin-8 (p = 0.05).</div></div><div><h3>Conclusion</h3><div>The results suggest that BMI contributes to GMV alterations in PCC patients, with both BMI and GMV demonstrating correlations with peripheral immunological markers. These findings indicate that converging mechanisms involving inflammation and structural brain alterations may contribute to obesity and PCC.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101137"},"PeriodicalIF":3.5,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145521107","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":"Serotonin and neurofilament light chain in alcohol-related suicide: Preliminary case observations","authors":"Shao-Cheng Wang ,&nbsp;Chih-Hui Wang ,&nbsp;Tung-Hsia Liu ,&nbsp;Hsian-Wei Kuo ,&nbsp;Yu-Li Liu","doi":"10.1016/j.bbih.2025.101136","DOIUrl":"10.1016/j.bbih.2025.101136","url":null,"abstract":"<div><div>Alcohol dependence significantly impacts both physiological and psychological health and is strongly linked to increased suicide attempt. However, the neurobiological mechanisms connecting alcohol use disorder (AUD) to suicidality remain inadequately understood. This study evaluated the severity of alcohol dependence in 24 patients diagnosed with AUD using the Alcohol Use Disorders Identification Test (AUDIT). In parallel, peripheral blood levels of neurofilament light chain (NfL), a bioindicator of neuronal injury, and serotonin, a neurotransmitter implicated in mood regulation and suicidality, were quantified. One patient with a prior history of suicide attempts exhibited markedly elevated plasma NfL levels (1350 pg/ml), greatly exceeding the mean observed in non-suicidal AUD patients (33.06 pg/ml). Despite the absence of detectable brain abnormalities on imaging, the patient presented with a lumbar vertebral burst fracture, suggesting spinal cord trauma as the source of neuronal injury. Moreover, serotonin levels in this individual were substantially reduced (89.41 ng/ml) relative to the group average (340.5 ng/ml). These findings suggest that elevated NfL levels may reflect neural injury originating from spinal, rather than cerebral, sources in AUD patients with suicide attempts. Additionally, reduced serotonin levels may serve as a clinically useful bioindicator to stratify suicide attempt in this population.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101136"},"PeriodicalIF":3.5,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468665","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":"Plasma profiles of neurology-related proteins in at-risk mental state and first-episode psychosis: Associations with psychotic symptoms and cognitive performance","authors":"Martí Llaurador-Coll ,&nbsp;Itziar Montalvo ,&nbsp;Francesc Estrada ,&nbsp;Vanessa Sánchez-Gistau ,&nbsp;Henrik Zetterberg ,&nbsp;Javier Labad ,&nbsp;Andrea L. Benedet ,&nbsp;Elisabet Vilella","doi":"10.1016/j.bbih.2025.101134","DOIUrl":"10.1016/j.bbih.2025.101134","url":null,"abstract":"<div><h3>Background</h3><div>Early diagnosis of psychosis is crucial, and biomarker detection may provide insights into the pathophysiology of psychosis and the potential for the development of early diagnostic tools. In particular, blood-based proteomic profiling has yielded promising results for psychiatric disorders because of the use of novel high-throughput techniques and the feasibility of performing blood extractions in routine clinical practice.</div></div><div><h3>Study design and methodology</h3><div>Here, we studied 182 participants (33.3 % females, <span><math><mrow><mover><mi>X</mi><mo>‾</mo></mover></mrow></math></span>_age = 24.66 ± 5.05), comprising 50 healthy controls (HCs), 37 patients with an at-risk mental state (ARMS) and 95 patients with a first episode of psychosis (FEP). We used a panel of 92 neurology-related proteins in a multiplex immunoassay to identify the plasma protein profiles of each group, their coexpression patterns and biological relevance, and their associations with psychotic symptoms and cognitive performance.</div></div><div><h3>Results</h3><div>CPA2 was overexpressed in both ARMS participants (β = 0.876, adj. p = 0.009) and FEP participants (β = 0.568, adj. p = 0.011) compared with HCs. In FEP participants, in addition to CPA2, 31 other proteins were overexpressed, with GFRA1 being the most differentially expressed protein (β = 1.159, adj. p &lt; 0.001). Coexpression clusters in FEP patients were involved in several biological processes, such as the regulation of myelination, cell adhesion, multicellular organismal processes and axon guidance. In ARMS patients, THY1 expression was inversely correlated with symptom severity (ρ = −0.640, adj. p = 0.039), and IL12 expression was correlated with cognitive performance (ρ = 0.707, adj. p = 0.007); however, no further correlations were found after the false discovery rate adjustment.</div></div><div><h3>Conclusions</h3><div>Our findings suggest the involvement of CPA2, GFRA1 and IL12, among other neurology-related proteins, in the early phases of psychosis, which, if confirmed, could become promising biomarkers for diagnosis, psychotic symptom development and psychosis-associated cognitive impairment. However, future studies with larger samples, a longitudinal design, and more extensive proteomic panels are needed to validate these biomarkers and refine their clinical applicability.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101134"},"PeriodicalIF":3.5,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468663","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":"Natural-cause mortality and C-reactive protein levels in patients with schizophrenia spectrum disorders: A prospective total cohort study","authors":"F. Fathian ,&nbsp;I. Divkovic ,&nbsp;M. Fagerbakke Strømme ,&nbsp;A. Mykletun ,&nbsp;R.A. Kroken ,&nbsp;C.A. Bartz-Johannessen ,&nbsp;E. Johnsen","doi":"10.1016/j.bbih.2025.101133","DOIUrl":"10.1016/j.bbih.2025.101133","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia spectrum disorders (SSD) are associated with an excess mortality risk compared with the general population. The involvement of low-grade inflammation and elevated C-reactive protein (CRP) levels is well established in SSD. However, associations between CRP and mortality risk in SSD are less investigated.</div></div><div><h3>Aim</h3><div>To investigate the association between the baseline CRP level and natural-cause mortality risk in SSD.</div></div><div><h3>Methods</h3><div>We included all patients with an SSD diagnosis and baseline CRP measurement from an open cohort study of consecutively admitted patients to a psychiatric acute unit at Haukeland University Hospital, Bergen, Norway, between May 1, 2005 and June 15, 2014. All patients were followed until the time of death or censoring/study end, up to 18.6 years, and only the assessments at admission were the focus of the present study. A competing risk model was used, adjusting for age and sex.</div></div><div><h3>Results</h3><div>Among 1315 individuals, 245 (19 %) died of natural causes; among these patients, 66 (27 %) deaths were related to cardiovascular disease (CVD). Elevated baseline CRP levels of 1.0 ≤ CRP &lt;3.0 mg/L were significantly associated with increased natural-cause mortality risk (adjusted hazard ratio [AHR], 1.88; 95 % confidence interval [CI], 1.22–2.88; p-value, 0.004), with a stronger association for CRP ≥3.0 mg/L (AHR, 2.28; 95 % CI, 1.50–3.48; p-value, &lt;0.001), compared with patients with CRP &lt;1.0 mg/L. Moreover, baseline CRP ≥3.0 mg/L was associated with increased CVD-related mortality risk (AHR, 3.12; 95 % CI, 1.16–8.41; p-value, 0.024).</div></div><div><h3>Conclusions</h3><div>Elevated CRP levels were associated with increased natural-cause mortality and, specifically, with CVD-related mortality risk. The CRP level may thus be considered a predictive factor in mortality risk scoring algorithms in SSD.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101133"},"PeriodicalIF":3.5,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468667","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":"Baicalein alleviates long-term cognitive impairments induced by repeated neonatal sevoflurane exposure via inhibition of cortical microglial TLR4/NF-kB signaling","authors":"Yingqiao Niu ,&nbsp;Qiuting Zeng ,&nbsp;Yan Yang ,&nbsp;Wenbo Liu ,&nbsp;Hui Zhang ,&nbsp;Shuyu Chen ,&nbsp;Xiaomin Li","doi":"10.1016/j.bbih.2025.101126","DOIUrl":"10.1016/j.bbih.2025.101126","url":null,"abstract":"<div><div>Sevoflurane, a widely used pediatric anesthetic, has been associated with long-term cognitive impairments following repeated neonatal exposure. Baicalein, a flavonoid derived from Scutellaria baicalensis, exhibits neuroprotective and anti-inflammatory properties. This study evaluated whether baicalein can mitigate sevoflurane-induced neuroinflammation and cognitive deficits in developing rats. Neonatal rats were exposed to sevoflurane (3 %, 2 h/day) from postnatal day (P) 6 to P8. In the intervention group, baicalein (50 mg/kg) was administered intraperitoneally from P6 to P8 and orally via drinking water from P21 to P35. Cognitive performance was assessed between P35 and P40 using the open field test, novel object recognition, and fear conditioning paradigms. Brain tissues were collected for Western blot, ELISA, and immunofluorescence analyses. Baicalein treatment significantly attenuated sevoflurane-induced deficits in memory and learning, particularly in the novel object recognition and fear conditioning tasks. Mechanistically, baicalein inhibited microglial activation, reduced cortical expression of TLR4 and phosphorylated NF-κB p65, and decreased pro-inflammatory mediators including iNOS, IL-1β, and IL-6 at P8. These findings indicate that repeated neonatal sevoflurane exposure impairs cognitive function via microglial-mediated neuroinflammation, and that baicalein's neuroprotective effect is at least partly attributable to modulation of cortical microglial activity via TLR4/NF-κB signaling. This study highlights baicalein as a promising therapeutic strategy to prevent long-term neurodevelopmental deficits in neonates.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101126"},"PeriodicalIF":3.5,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468666","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}