Brain, behavior, & immunity - health最新文献

{"title":"Targeting glycolysis for neuroprotection in early LPS-induced neuroinflammation","authors":"Adriana Fernanda K. Vizuete ,&nbsp;Fernanda Fróes ,&nbsp;Marina Seady ,&nbsp;Aline Castro Caurio ,&nbsp;Osmar Vieira Ramires Junior ,&nbsp;Ana Karla Oliveira Leite ,&nbsp;Clarissa Penha Farias ,&nbsp;Angela T.S. Wyse ,&nbsp;Carlos-Alberto Gonçalves","doi":"10.1016/j.bbih.2024.100901","DOIUrl":"10.1016/j.bbih.2024.100901","url":null,"abstract":"<div><div>Neuroinflammation is a pathophysiological feature of numerous neurological and psychiatric disorders. The immune response in the central nervous system, driven by microglia and astrocytes, leads to metabolic reprogramming towards aerobic glycolysis, a phenomenon known as the Warburg effect. The control of metabolic reprogramming via immunomodulation may represent a potential therapeutic target for providing protection against neuroinflammation, which contributes to neuronal dysfunction and death in several neurological disorders. For this purpose, we investigated putative neuroprotective effects of the downregulation of aerobic glycolysis using the 3PO inhibitor, and the downregulation of neuroinflammation using MCC950, in the early LPS-induced neuroinflammation model. The LPS-induced shift towards glycolysis, inflammatory and glial changes (IL-1β, NF-κB, COX2, Iba1, GFAP) were reversed by 3PO, which improved animal behavior. Additionally, MCC950 (an NLRP3 inhibitor) downregulated TLR4/Akt/p38 MAPK/NF-κB/STAT3 signaling, expressions of COX2 and IL-1β, and the astrocyte reactivity (decreasing GFAP) induced by early neuroinflammation, resulting in low glucose uptake. Our data support the occurrence of the Warburg effect during early neuroinflammation and suggest potential new approaches for the treatment of brain injury, given the role of neuroinflammation in such events.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100901"},"PeriodicalIF":3.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective role of TRPV1+ nociceptive neurons communication to macrophages against T. cruzi infection in mice","authors":"Sergio M. Borghi ,&nbsp;Aparecida D. Malvezi ,&nbsp;Maria Isabel Lovo-Martins ,&nbsp;Victor Fattori ,&nbsp;Tiago H. Zaninelli ,&nbsp;Mariana M. Bertozzi ,&nbsp;Camila R. Ferraz ,&nbsp;Thiago M. Cunha ,&nbsp;Rubia Casagrande ,&nbsp;Marli C. Martins-Pinge ,&nbsp;Phileno Pinge-Filho ,&nbsp;Waldiceu A. Verri Jr.","doi":"10.1016/j.bbih.2024.100897","DOIUrl":"10.1016/j.bbih.2024.100897","url":null,"abstract":"<div><div>Chagas’ disease is a life-threatening condition caused by <em>Trypanosoma cruzi</em>. Patients with chronic disease may develop gastrointestinal, neurological, or associated neuro-digestive dysfunctions. CNS invasion by <em>T. cruzi</em> can occur in the acute phase, and its presence in the brain and cerebrospinal fluid was reported. <em>T. cruzi</em> induces nociceptor neuron activation and pain. Nociceptive neurons and macrophage interact in diseases, and this neuroimmune communication has a pivotal role in disease outcome. We investigated, the role of TRPV1⁺ neurons in experimental <em>T. cruzi</em> infection in mice. <em>T. cruzi</em> forms were observed in the DRG and spinal cord in early stages of acute infection, and intrathecal administration of <em>T. cruzi</em> antigens into spinal cord induced pain. <em>Trpv1</em> mRNA expression was increased in the DRG of infected mice and targeting TRPV1 reduced <em>T. cruzi</em>-induced pain. TRPV1 nociceptor ablation increased blood parasitemia while TRPV1 knockout mice presented 50% mortality upon infection in a normally non-lethal model. TRPV1 knockout also worsened clinical outcomes (hepatomegaly and megacecum), increased plasmatic Th2 cytokines and nitrite in cardiac tissue, and reduced heart leukocyte infiltration. Conditioned media of capsaicin-stimulated DRG neurons decreased macrophage internalization of <em>T. cruzi</em>, and CGRP receptor antagonism in infected mice reduced pain, increased early parasitemia and promoted 18% mortality. This indicates that soluble mediators released upon nociceptor activation such as CGRP increase macrophage ability to control disease outcome. These data unveil TRPV1⁺ neurons release CGRP to limit macrophage internalization of <em>T. cruzi</em>, triggering protective mechanisms against <em>T. cruzi</em> infection.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100897"},"PeriodicalIF":3.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BDNF methylation associated with stress in women: Novel insights in epigenetics and inflammation","authors":"Luciana Fungaro Rissatti ,&nbsp;David Wilson ,&nbsp;Fanny Palace-Berl ,&nbsp;Bárbara de Mello Ponteciano ,&nbsp;Flávia Sardela de Miranda ,&nbsp;Ivana Alece Arantes Moreno ,&nbsp;Tamires dos Santos Vieira ,&nbsp;Bruna Pereira Sorroche ,&nbsp;Lidia Maria Rebolho Batista Arantes ,&nbsp;Adriana Madeira Alvares da Silva ,&nbsp;Vânia D'Almeida ,&nbsp;Marcelo Demarzo ,&nbsp;Daniela Rodrigues de Oliveira","doi":"10.1016/j.bbih.2024.100900","DOIUrl":"10.1016/j.bbih.2024.100900","url":null,"abstract":"<div><div>The brain-derived neurotrophic factor (BDNF) gene plays an important role in modulating the stress-response axis and inflammation, which can be regulated by epigenetic mechanisms. BNDF methylation has been associated with stress-related psychiatric disorders such as depression, anxiety and post-traumatic stress. Previous studies have reported that stressful events are involved with long-lasting alterations in DNA methylation (DNAm) of the BNDF exon IV promoter, suggesting that glucocorticoids and inflammatory cytokines can regulate this process. We previously found that perceived psychological stress is modulated by inflammatory cytokines, such as interleukin (IL)-6, IL-8 and IL-10, and IL-12p70, suggesting their role in mediating the stress response. However, the epigenetic mechanism mediating this response has yet to be fully understood. In this study, we propose that high perceived stress and high serum levels of inflammatory cytokines may correlate with specific methylation sites within the BNDF exon IV promoter. To address these questions, we conducted a cross-sectional study of 82 adult women teachers working in basic education in Brazil. The perceived stress scale was used to assess stress and blood samples were collected for the measurement of inflammatory markers and BNDF methylation through flow cytometry assay and DNA pyrosequencing, respectively. We detected differentially methylated CpG sites in the <em>BNDF</em> gene, where 5 CpG sites were directly correlated with high stress levels. However, 4 CpG sites showed inverse effects, indicating that changes in methylation levels in those sites could lead to a protective effect on perceived stress. About inflammatory markers, IL-6 and IL-8 were associated with high perceived stress. However, only IL-8 and IL-10 showed simultaneous modulation of perceived stress, while IL-10 and IL12p70 correlated with DNAm. We found that higher levels in IL-10 and IL-12p70 serum decrease methylation in CpG11. A direct relationship was also found to IL-12p70, where higher levels in serum increase methylation in CpG5 and 13, respectively. Taken as a whole, our findings reinforce the hypothesis regarding stress-sensitive regions within the BDNF gene, mainly for CpG5, 11, and 13. In addition to these results, CpG7 and 9 may be regarded as stress-protective regions. Our data suggest that BDNF DNAm in the blood may represent a novel biomarker for early detection of adverse effects of chronic exposure to stress in healthy individuals.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100900"},"PeriodicalIF":3.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic stress modulates the expression level of leptin and leptin receptors in the hypothalamus of male rats with a history of maternal stress","authors":"Roya Hosseini ,&nbsp;Sara Emadian ,&nbsp;Manijeh Dogani ,&nbsp;Touba Ghazanfari ,&nbsp;Nayere Askari","doi":"10.1016/j.bbih.2024.100895","DOIUrl":"10.1016/j.bbih.2024.100895","url":null,"abstract":"<div><div>The activity of different neurotransmitter pathways in the hypothalamus controls the stress response. Meanwhile, leptin is known as an effective mediator in the stress response, and its serum and brain levels change when exposed to stressful factors. In this study, the effect of chronic social instability stress (INS) and chronic unpredictable stress (CUS) on anxiety-like behavioral responses and the level of expression of leptin and its receptor in the brain of male Wistar rats that were under maternal stress (MS) were investigated. Grouping: control (n = 7), MS (n = 7), INS (n = 7), CUS (n = 7), MS + INS (n = 7), MS + CUS (n = 7). Forced swimming, elevated plus-maze, and open field tests were used to check anxiety-like behaviors. Next, the mRNA expression of leptin and its receptor in the hypothalamus was measured by Real-Time PCR. According to the results, adult rats with maternal stress showed an increase in their anxiety-like behaviors faced with the stress of chronic social instability and chronic unpredictable stress (compared to the groups that only received adult stresses). Also, the hypothalamic expression of leptin decreased, but we saw an increase in the expression of hypothalamic leptin receptors in INS, CUS, and MS groups and a decrease in MS + INS and MS + CUS groups. Results of this research suggest that leptin plays a role as an effective mediator in the occurrence of central and behavioral changes caused by maternal stress. In other words, it can be effective in changing resilience in the face of adult stress.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100895"},"PeriodicalIF":3.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing doxycycline for Alzheimer's treatment: Challenges from a nano-based drug delivery perspective","authors":"Mariana Conceição ,&nbsp;Leonardo Delello Di Filippo ,&nbsp;Jonatas Lobato Duarte ,&nbsp;Fernando Pereira Beserra ,&nbsp;Maria Palmira Daflon Gremião ,&nbsp;Marlus Chorilli","doi":"10.1016/j.bbih.2024.100894","DOIUrl":"10.1016/j.bbih.2024.100894","url":null,"abstract":"<div><div>Drug repurposing, also known as drug repositioning, involves identifying new applications for drugs whose effects in a disease are already established. Doxycycline, a broad-spectrum antibiotic belonging to the tetracycline class, has demonstrated potential activity against neurodegenerative diseases like Alzheimer's and Parkinson's. However, despite its promise, the repurposed use of doxycycline encounters challenges in reaching the brain in adequate concentrations to exert its effects. To address this issue, nanostructured systems offer an innovative approach that can enhance brain targeting and the desired therapeutic outcomes. This review discusses the advances in doxycycline repurposing for Alzheimer's disease, presenting physicochemical and biological aspects that permeate doxycycline's repositioning and its application in nano-based delivery systems.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100894"},"PeriodicalIF":3.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between uric acid and depressive symptoms, and the mediating role of immunoinflammatory: Findings from rural older adults","authors":"Yating Luo ,&nbsp;Sha Wang ,&nbsp;Qinqin Cheng ,&nbsp;Jing Li ,&nbsp;Huiyi Zhang ,&nbsp;Jingying Wang ,&nbsp;Juan Luo ,&nbsp;Chen Pan ,&nbsp;Qiuxiang Zhang ,&nbsp;Jianfei Xie ,&nbsp;Andy S.K. Cheng","doi":"10.1016/j.bbih.2024.100893","DOIUrl":"10.1016/j.bbih.2024.100893","url":null,"abstract":"<div><h3>Background</h3><div>In the low-resource rural areas, older adults may experience prolonged and severe depressive symptoms. This study aimed to investigate the relationship between uric acid, depressive symptoms and immunoinflammatory among rural older adults.</div></div><div><h3>Method</h3><div>This case-control study was conducted in 17 rural villages in Hunan Province, China, between January 2023 and April 2024. This study included 180 participants: (1) Rural Older Adults with Depressive Symptoms group:90 patients with first-time diagnosed with depressive symptoms (Geriatric Depression Scale-15, GDS-15 ≥ 5 scores); (2) Control group: 90 individually matched (age and sex) healthy subjects (GDS-15 &lt; 5 scores) who were aged ≥60 years.</div></div><div><h3>Results</h3><div>Both males and females, depressive symptoms were associated with higher uric acid levels and C-reactive protein levels (All <em>P</em> &lt; 0.05). Whereas in females, depressive symptoms were also linked to higher procalcitonin (<em>P</em> = 0.005) and serum amyloid A (<em>P</em> = 0.008) levels. In addition, C-reactive protein plays a significant mediating role between uric acid and depressive symptoms in males.</div></div><div><h3>Conclusion</h3><div>Further investigation is necessary to clarify the underlying mechanisms, examine gender-specific disparities, and assess potential therapeutic interventions targeting uric acid and inflammation levels to mitigate mental disorders risk.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100893"},"PeriodicalIF":3.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical features and predictive nomogram for fatigue sequelae in non-severe patients infected with SARS-CoV-2 Omicron variant in Shanghai, China","authors":"Xiao-Lei Shen ,&nbsp;Yu-Han Jiang ,&nbsp;Shen-Jie Li,&nbsp;Xin-Yi Xie,&nbsp;Yu Cheng,&nbsp;Li Wu,&nbsp;Jun Shen,&nbsp;Wei Chen,&nbsp;Jian-Ren Liu","doi":"10.1016/j.bbih.2024.100889","DOIUrl":"10.1016/j.bbih.2024.100889","url":null,"abstract":"<div><h3>Background</h3><div>Patients with coronavirus disease 2019(COVID-2019) infections may still experience long-term effects, with fatigue being one of the most frequent ones. Clinical research on the long COVID in the Chinese population after infection is comparatively lacking.</div></div><div><h3>Objective</h3><div>To collect and analyze the long-term effects of non-severe COVID-19 infection patients and to develop a model for the prediction of fatigue symptoms.</div></div><div><h3>Methods</h3><div>223 non-severe COVID-19 patients admitted to one designated hospital were enrolled after finish all the self-designed clinical information registration form and nine-month follow-up. We explored the frequency and symptom types of long COVID. Correlation analysis was done on the neuropsychological scale results. After cluster analysis, lasoo regression and logistic regressions, a nomogram prediction model was produced as a result of investigating the risk factors for fatigue.</div></div><div><h3>Results</h3><div>A total of 108 (48.4%) of the 223 non-severe COVID-19 patients reported sequelae for more than 4 weeks, and of these, 35 (15.7%) had fatigue sequelae that were scale-confirmed. Other sequelae of more than 10% were brain fog (<em>n</em> = 37,16.6%), cough (<em>n</em> = 26,11.7%) and insomnia (n = 23,10.3%). A correlation between depression and fatigue was discovered following the completion of neuropsychological scale. The duration of hospitalization, the non-use of antiviral medications in treatment, IL-6 and CD16+CD56⁺ cell levels in blood are the main independent risk factors and predictors of fatigue sequelae in long COVID. Additionally, the neurology diseases and vaccination status may also influence the fatigue sequelae.</div></div><div><h3>Conclusion</h3><div>Nearly half of the patients infected with COVID-19 Omicron variant complained of sequelae, and fatigue was the most common symptom, which was correlated with depression. Significant predictors of fatigue sequelae included length of hospitalization, non-use of antiviral drug, and immune-related serum markers of IL-6 and CD16+CD56⁺ NK cell levels. The presence of neurology diseases and a lack of vaccination could also predict the occurrence of fatigue sequelae.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100889"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation is associated with pain and fatigue in older adults","authors":"Sara A. Norton ,&nbsp;Lauren M. Blaydon ,&nbsp;Megan Niehaus ,&nbsp;Alex P. Miller ,&nbsp;Patrick L. Hill ,&nbsp;Thomas F. Oltmanns ,&nbsp;Ryan Bogdan","doi":"10.1016/j.bbih.2024.100874","DOIUrl":"10.1016/j.bbih.2024.100874","url":null,"abstract":"<div><h3>Introduction</h3><div>Increasing evidence suggests that inflammation may play a pivotal role in the development of chronic pain and fatigue in aging individuals. This study investigated the relationship between three inflammatory markers (IL-6, CRP, and TNFα) and pain and fatigue, both cross-sectionally and longitudinally, in a sample of older adults from the Saint Louis Personality and Aging (SPAN) study.</div></div><div><h3>Methods</h3><div>SPAN study participants provided blood samples at two in-person sessions approximately 2 years apart for the analysis of the inflammatory biomarkers IL-6, CRP, and TNFα. Pain and fatigue were assessed using the RAND-36 Health Status Inventory. Correlations (with false discovery rate correction for multiple testing) and follow-up linear regressions including potentially confounding demographic (e.g., annual household income) and health (e.g., BMI, medication use) covariates were used to estimate cross sectional and longitudinal associations. Analytic ns ranged from 533 to 815.</div></div><div><h3>Results</h3><div>Cross-sectional analyses revealed that higher IL-6 and CRP were associated with greater reported pain and fatigue, even after accounting for covariates (βs &gt; .098, <em>p</em>s &lt; .05). TNFα was associated with greater fatigue only (β = .100, <em>p</em> = .012). Longitudinally, CRP and IL-6 predicted future pain and fatigue, although only the relationship between CRP and future fatigue survived the inclusion of covariates (β = .104, <em>p</em> = .022). Both pain and fatigue predicted higher levels of IL-6 and CRP approximately 2 years later, although only the associations with IL-6 survived the inclusion of covariates (βs &gt; .12, <em>ps</em> &lt; .01).</div></div><div><h3>Discussion</h3><div>Our study adds to a growing body of literature showing that inflammation is associated with greater pain and fatigue in older adults. Our longitudinal data showing temporal bidirectional associations is consistent with evidence from non-human animal models that heightened inflammation causally contributes to fatigue and also suggests that the experience of pain and fatigue may contribute to inflammation. It will be important for future work to identify how lifestyle factors associated with pain and fatigue (e.g., physical activity) may contribute to these associations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100874"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage","authors":"Beibei Xu ,&nbsp;Hao Li ,&nbsp;He Zheng ,&nbsp;Zhongyu Gao ,&nbsp;Zhigang Miao ,&nbsp;Xingshun Xu ,&nbsp;Hao Yang ,&nbsp;Yi Yang","doi":"10.1016/j.bbih.2024.100890","DOIUrl":"10.1016/j.bbih.2024.100890","url":null,"abstract":"<div><div>Interleukin 18 (IL-18), a proinflammatory cytokine, has been implicated in various neurological disorders, including cerebrovascular disease and psychiatric disorders. In a previous study, IL-18 was observed to activate microglia and enhance the inflammatory response following intracranial hemorrhage (ICH). However, the underlying mechanism remains unclear. In the present study, we found that IL-18 and IL-18 receptor (IL-18 R) are primarily secreted by neurons during the early stages after ICH, with microglia becoming the predominant source at 12–24 h after ICH. Meanwhile, the expression level of IL-18 R increased following ICH, along with an augmentation in the binding affinity of IL-18 R to IL-18. Subsequently, the deficiency of IL-18 R mitigated neurological impairment and subsequent activation of inflammatory pathways in mice post-ICH. Moreover, our findings suggest that IL-18-induced neurological injury after ICH may be mediated by the interaction between IL18R and NKCC1. Significantly, the NKCC1 inhibitor rescued the neurologic injury after ICH. In conclusion, our study suggests that targeting the IL-18/IL-18R/NKCC1 pathway could be an effective therapeutic strategy to attenuate secondary brain injury after ICH.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100890"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contributions of maternal prenatal infection and antibiotic exposure to offspring infection and risk for allergic respiratory conditions through age 5","authors":"Shannon K. Murphy ,&nbsp;Madeline R. Pike ,&nbsp;Emily Lipner ,&nbsp;Seth D. Maxwell ,&nbsp;Barbara A. Cohn ,&nbsp;Piera Cirillo ,&nbsp;Nickilou Y. Krigbaum ,&nbsp;Elizabeth C. Breen ,&nbsp;Lauren M. Ellman","doi":"10.1016/j.bbih.2024.100892","DOIUrl":"10.1016/j.bbih.2024.100892","url":null,"abstract":"<div><h3>Objectives</h3><div>To determine if maternal prenatal infection increases risk of offspring postnatal infections through age 5 or diagnosis of respiratory allergy at age 5, independent of prenatal/postnatal antibiotic exposure. To evaluate if frequency of offspring infections mediates an association between prenatal infection and respiratory allergy at age 5.</div></div><div><h3>Study design</h3><div>Secondary data analyses were performed from the Child Health and Development Studies (CHDS), a prospective, longitudinal birth cohort that enrolled pregnant women from 1959 to 1966 (N = 19,044 live births). The sample included a subset of mother-offspring dyads (<em>n</em> = 2062) with abstracted medical record data from the prenatal period through age 5 that included information on antibiotic use, infection, and offspring respiratory allergy.</div></div><div><h3>Results</h3><div>Second trimester maternal infection was associated with an increased risk of offspring infection (IRR = 1.23; 95% CI = 1.09–1.39; <em>p</em> = 0.001). No significant direct associations were detected between prenatal infection and diagnosis of offspring respiratory allergy. Offspring infection (OR = 1.17; 95% CI = 1.13–1.20; <em>p</em> &lt; 0.001) and antibiotic exposure (OR = 1.28; 95% CI = 1.22–1.33; <em>p</em> &lt; 0.001) were significantly associated with a diagnosis of offspring respiratory allergy. Respiratory allergy diagnosis risk was greater with increasing offspring infection exposure and antibiotics. There was a significant indirect effect of second trimester maternal infection on offspring respiratory allergy, due to infections and not antibiotic use, via offspring infection, indicating a partially mediated effect.</div></div><div><h3>Conclusion</h3><div>Prenatal maternal infection may contribute to increase risk for early childhood infections, which in turn, may increase risk for allergic conditions.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100892"},"PeriodicalIF":3.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}