Brain Research Bulletin最新文献

{"title":"EEG microstate in people with different degrees of fear of heights during virtual high-altitude exposure","authors":"Chaolin Teng ,&nbsp;Lin Cong ,&nbsp;Qiumei Tian ,&nbsp;Ke Liu ,&nbsp;Shan Cheng ,&nbsp;Taihui Zhang ,&nbsp;Weitao Dang ,&nbsp;Yajing Hou ,&nbsp;Jin Ma ,&nbsp;Duoduo Hui ,&nbsp;Wendong Hu","doi":"10.1016/j.brainresbull.2024.111112","DOIUrl":"10.1016/j.brainresbull.2024.111112","url":null,"abstract":"<div><div>Previous neuroimaging studies based on electroencephalography (EEG) microstate analysis have identified abnormal neural electric activity in patients with psychiatric diseases. However, the microstate information in individuals with different degrees of fear of heights (FoH) remains unknown so far. The aim of the study was therefore to explore the changes of EEG microstate characteristics in different FoH individuals when exposed to high-altitude stimulated by virtual reality (VR). First, acrophobia questionnaire (AQ) before the experiment and 32-channel EEG signals under the virtual high-altitude exposure were collected from 69 subjects. Second, each subject was divided into one of three levels of FoH including no-FoH, mild or moderate FoH (m-FoH) and severe FoH (s-FoH) groups according to their AQ scores. Third, using microstate analysis, we transformed EEG data into sequences of characteristic topographic maps and computed EEG microstate features including microstate basic parameters, microstate sequences complexity and microstate energy. Finally, the extracted features as inputs were sent to train and test an support vector machine (SVM) for classifying different FoH groups. The results demonstrated that five types of microstates (labeled as A, B, C, D and F) were identified across all subjects, of which microstates A-D resembled the four typical microstate classes and microstate F was a non-canonical microstate. Significantly decreased occurrence, coverage and duration of microstate F and transition probabilities from other microstates to microstate F in m-FoH and s-FoH groups were observed compared to no-FoH group. It was also demonstrated that both m-FoH and s-FoH groups showed a notable reduction in sample entropy and Lempel-Ziv complexity. Moreover, energies of microstate D for m-FoH group and microstate B for s-FoH group in right parietal, parietooccipital and occipital regions exhibited prominent decreases as comparison to people without FoH. But, no significant differences were found between m-FoH and s-FoH groups. Additionally, the results indicated that AQ-anxiety scores were negatively correlated with microstate basic metrics as well as microstate energy. For classification, the performance of SVM reached a relatively high accuracy of 89 % for distinguishing no-FoH from m-FoH. In summary, the findings highlight the alterations of EEG microstates in people with fear of heights induced by virtual high-altitude, reflecting potentially underlying abnormalities in the allocation of neural assemblies. Therefore, the combination of EEG microstate analysis and VR may be a potential valuable approach for the diagnosis of fear of heights.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"218 ","pages":"Article 111112"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Correlations among serum alpha-(1,6)-fucosyltransferase and early symptoms associated with Parkinson's disease: A cross-sectional retrospective study” [Brain Res. Bull. 212 (2024) 110959]","authors":"Qi-rong Wang ,&nbsp;Xue Yu ,&nbsp;Yang Li ,&nbsp;Ming-zhen Zhu","doi":"10.1016/j.brainresbull.2024.111099","DOIUrl":"10.1016/j.brainresbull.2024.111099","url":null,"abstract":"","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"218 ","pages":"Article 111099"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ablation of NAMPT in dopaminergic neurons leads to neurodegeneration and induces Parkinson’s disease in mouse","authors":"Cong Chen ,&nbsp;Tong Wang ,&nbsp;Tong-Yao Gao ,&nbsp;Ya-Ling Chen ,&nbsp;Yun-Bi Lu ,&nbsp;Wei-Ping Zhang","doi":"10.1016/j.brainresbull.2024.111114","DOIUrl":"10.1016/j.brainresbull.2024.111114","url":null,"abstract":"<div><div>Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme in the salvaging synthesize pathway of nicotinamide adenine dinucleotide (NAD). The neuroprotective roles of NAMPT on neurodegeneration have been explored in aging brain and Alzheimer’s Disease. However, its roles in Parkinson’s Disease (PD) remain to be elucidated. We found that the dopaminergic neurons in substantia nigra expressed higher levels of NAMPT than the other types of neurons. Using conditional knockout of the <em>Nampt</em> gene in dopaminergic neurons and utilizing a NAMPT inhibitor in the substantia nigra of mice, we found that the NAMPT deficiency triggered the time-dependent loss of dopaminergic neurons, the impairment of the dopamine nigrostriatal pathway, and the development of PD-like motor dysfunction. In the rotenone-induced PD mouse model, nicotinamide ribose (NR), a precursor of NAD, rescued the loss of dopaminergic neurons, the impairment of dopamine nigrostriatal pathway, and mitigated PD-like motor dysfunction. In SH-SY5Y cells, NAD suppression induced the accumulation of reactive oxygen species (ROS), mitochondrial impairment, and cell death, which was reversed by N-acetyl cysteine, an antioxidant and ROS scavenger. Rotenone decreased NAD level, induced the accumulation of ROS and the impairment of mitochondria, which was reversed by NR. In summary, our findings show that the ablation of NAMPT in dopaminergic neurons leads to neurodegeneration and contributes to the development of PD. The NAD precursors have the potential to protect the degeneration of dopaminergic neurons, and offering a therapeutic approach for the treatment of PD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"218 ","pages":"Article 111114"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The extremely low-frequency electromagnetic field (50 Hz) can establish a new “set-point” for the activity of the locus coeruleus–noradrenergic (LC-NA) system in rat","authors":"Angelika Klimek ,&nbsp;Hanna Kletkiewicz ,&nbsp;Agnieszka Siejka ,&nbsp;Joanna Wyszkowska ,&nbsp;Justyna Maliszewska ,&nbsp;Maciej Klimiuk ,&nbsp;Milena Jankowska ,&nbsp;Justyna Rogalska","doi":"10.1016/j.brainresbull.2024.111111","DOIUrl":"10.1016/j.brainresbull.2024.111111","url":null,"abstract":"<div><div>Exposure of organisms to extremely low-frequency electromagnetic field (ELF-EMF; 50 Hz) has been increasing in recent decades, which is connected with dynamic technological development. ELF-EMF is considered a stress factor and its effects on organisms are still being investigated. We aimed to determine its impact on the locus coeruleus–noradrenergic (LC-NA) system enabling adaptation to stressful conditions. For this purpose, we exposed rats to 50 Hz ELF-EMF of 1 and 7 mT, 1 h/day for 7 days. The procedure was repeated three times to examine the organism's adaptive capabilities. Subsequently, the concentration of adrenaline, noradrenaline and its metabolite MHPG as well as the expression of the β2-adrenergic receptor was assessed. After the end of each exposure, part of the animals were subjected to a behavioural test to assess the influence of repeated ELF-EMF exposure on stress response to subsequent stress factors. Our research proved that mechanisms underlying the effects of ELF-EMF on stress response include the LC-NA system. ELF-EMF of 1 mT induced adaptive changes in the NA-LC system. However, exposure to 7 mT caused increased activity of the stress system which resulted in sensitization to subsequent, heterotypic (different from the one previously acting) stress factor. As ELF-EMF of 7 mT caused a profound decrease in β2-AR level would strongly inhibit the potential for neuroplastic processes in the hippocampus. Moreover, rats exposed to ELF-EMF of 7 mT showed moderately increased anxiety-related behaviour. Disturbances in NA-LC transmission may underlie the development of some neurodegenerative and psychiatric diseases which indicates the possible involvement of ELF-EMF in the pathogenesis of these disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"219 ","pages":"Article 111111"},"PeriodicalIF":3.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive dysfunction induced by cranial radiotherapy: mechanisms and therapeutic methods","authors":"Xuejiao Li,&nbsp;Zhongxiang Ding","doi":"10.1016/j.brainresbull.2024.111106","DOIUrl":"10.1016/j.brainresbull.2024.111106","url":null,"abstract":"<div><div>Cranial radiotherapy can damage normal brain tissues, inducing cognitive dysfunction in patients. Radiotherapy-induced cognitive dysfunction is associated with hippocampal injury, white matter damage and microvascular injury. In this study, the mechanisms of cognitive dysfunction induced by cranial radiotherapy and combined chemoradiotherapy are reviewed, and the advances in therapeutic methods for radiotherapy-induced brain injury are summarized. The mechanisms of radiotherapy-induced brain injury include a decline of neurogenesis, impairment of neurons and glial cells, vascular injury, oxidative stress and DNA damage, cell death, and inflammatory response. Disruption of the blood<img>brain barrier (BBB) increases the exposure of the brain to chemotherapeutic agents, thus exacerbating radiotherapy-induced brain damage. The current methods used to prevent radiotherapy-induced brain injury mainly include precision radiotherapy, stem cell transplantation, and treatment with neuroprotective drugs. The combined application of precision radiotherapy and neuroprotective drugs, including antioxidants, anti-inflammatory agents and other drugs, might exert better neuroprotective effects. To resolve the issues of neuroprotective drugs, such as difficulty in crossing the BBB, nanoenzymes and drug delivery nano-systems could be applied in the future.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"218 ","pages":"Article 111106"},"PeriodicalIF":3.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemia","authors":"Maysam Havasi Mehr ,&nbsp;Shahein Momenabadi ,&nbsp;Ali Vakili ,&nbsp;Abbas Pakdel ,&nbsp;Abbas Ali Vafaei ,&nbsp;Abedin Vakili","doi":"10.1016/j.brainresbull.2024.111103","DOIUrl":"10.1016/j.brainresbull.2024.111103","url":null,"abstract":"<div><div>The purpose of this research was to assess the impact of different doses of Daphnetin (DAP, a natural compound derived from coumarin) on hippocampus neuronal injury, neurobehavioral function, blood-brain barrier (BBB) integrity, expression of claudin-5, brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), and inflammatory markers in a mouse model of cerebral ischemia. Cerebral ischemia was induced in mice through 30 minutes of bilateral common carotid occlusion (BCCAO), followed by 48 hours of reperfusion. The viability of hippocampal neurons was assessed using Cresyl violet staining and BBB function was determined by measuring Evans blue (E.B) dye leakage. Spatial memory was tested using the Radial Arm Water Maze (RAWM) task. Claudin-5 and BDNF were measured by immunofluorescence, while SOD, interleukin-1 beta (IL-1β), and nuclear factor-κB (NF-κB) expression were determined through western blotting. Administering DAP significantly increased neuron survival in the hippocampus CA1, CA3, and dentate gyrus (DG) regions and improved spatial memory dose-dependently (P&lt;0.0001). Treatment with DAP (40 mg/kg IP) significantly reduced E.B leakage and brain water content (P&lt;0.001). Furthermore, it increased the claudin-5, BDNF, and SOD levels and diminished NF-κB and IL-1β expression (P&lt;0.0001). The research found that DAP protected neurons in the CA1, CA3, and DG areas of the hippocampus, enhanced behavioral functions, and preserved BBB integrity in a cerebral ischemia model. This positive impact is achieved by increasing the expression of claudin-5, BDNF, and SOD and diminishing neuroinflammation. Further research is required to clarify the mechanisms and possible clinical uses.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"218 ","pages":"Article 111103"},"PeriodicalIF":3.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orexin A protects against cerebral ischemia-reperfusion injury by enhancing reperfusion in ischemic cortex via HIF-1α-ET-1/eNOS pathway","authors":"Minxia Zhu,&nbsp;Xiaofeng Li,&nbsp;Jing Guo,&nbsp;Zhaojun Zhang,&nbsp;Xu Guo,&nbsp;Zhuoqi Li,&nbsp;Junwei Lin,&nbsp;Pengfei Li,&nbsp;Zixuan Jiang,&nbsp;Yifan Zhu","doi":"10.1016/j.brainresbull.2024.111105","DOIUrl":"10.1016/j.brainresbull.2024.111105","url":null,"abstract":"<div><div>The purpose of this study was to investigate the protective effect and underlying mechanism of orexin A on cerebral ischemia-reperfusion injury, specifically through vasodilation mediated by the hypoxia inducible factor-1α (HIF-1α)-Endothelin-1(ET-1)/endothelial nitric oxide synthase (eNOS) pathway. A model of middle cerebral artery occlusion was established in both wild-type SD rats with exogenous orexin A intervention and in orexin A transgenic rats. Neurological deficit scores and cerebral infarction areas were assessed, and ischemic cortical blood flow was monitored. Gene and protein expression levels of HIF-1α, HIF-2α, ET-1, and three types of NOS were detected using real-time RT-qPCR and Western blot analysis, respectively. Additionally, nitric oxide (NO) levels in the cortex were analyzed through biochemical detection methods. Orexin A demonstrated a protective effect by reducing cerebral infarction and improving neurological deficits, which was achieved by increasing cortical blood flow during reperfusion. This protective mechanism was associated with upregulated HIF-1α expression, downregulated ET-1 expression, upregulated eNOS expression, and increased NO production. This study demonstrates the protective effect of orexin A on cerebral ischemia-reperfusion injury, achieved by regulating the release of vasomotor substances to enhance cortical blood flow during reperfusion. These findings suggest that orexin A may represent a potential therapeutic strategy for ischemic stroke.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"218 ","pages":"Article 111105"},"PeriodicalIF":3.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABAB modulate NF-κB/NLRP3 pathways in electroacupuncture prevention of depression in CUMS rats","authors":"Jianguo Li ,&nbsp;Dong Yao ,&nbsp;Tiansheng Zhang ,&nbsp;Tao Tong ,&nbsp;Junliang Shen ,&nbsp;Simin Yan ,&nbsp;Jingyu Zeng ,&nbsp;Muhammad Shahzad Aslam ,&nbsp;Meng Li ,&nbsp;Zhuoran You ,&nbsp;Jingxuan Li ,&nbsp;Zhongwen Li ,&nbsp;Yizheng Li ,&nbsp;Chongyao Hao ,&nbsp;Xianjun Meng","doi":"10.1016/j.brainresbull.2024.111108","DOIUrl":"10.1016/j.brainresbull.2024.111108","url":null,"abstract":"<div><h3>Background</h3><div>Our previous research has demonstrated that electroacupuncture (EA) has the potential to mitigate depression-like symptoms resulting from chronic stress. However, further investigation is required to fully understand the underlying mechanisms. The regulatory role of γ-aminobutyric acid type B (GABA_B) in synaptic plasticity and the involvement of NF-κB/NLRP3-mediated inflammation in the lateral habenula nucleus (LHb) are key factors in the development of depression. This study sought to investigate the potential of EA in mitigating depression-like symptoms induced by chronic stress through mechanisms such as enhancing GABA_B levels, regulating synaptic plasticity in the LHb, and suppressing NF-κB/NLRP3-mediated inflammation.</div></div><div><h3>Methods</h3><div>Sprague-Dawley rats were exposed to chronic unpredictable mild stress (CUMS) in order to create a model of depression. Subsequently, the weight and behavioral assessments of all rats were monitored, and samples of the lateral habenula and serum were collected. The protein expression levels were analyzed using western blotting. The 5-hydroxytryptophan (5-HT), Dopamine (DA), and Norepinephrine (NE) in the LHb and serum were measured using ELISA. The alterations in GABA_B and NF-κB in the LHb were observed through immunofluorescence. The neuronal damage in the LHb was assessed using Nissl staining.</div></div><div><h3>Results</h3><div>EA upregulated the expression of GABA_B in the LHb of rats subjected to CUMS. Subsequent behavioral assessments indicated that blocking GABA_B attenuated the antidepressant effects of EA in CUMS-exposed rats. Furthermore, EA enhanced synaptic plasticity in the LHb of CUMS-exposed rats and mitigated NF-κB/NLRP3-mediated inflammatory responses, with these effects potentially being reversed by GABA_B inhibition.</div></div><div><h3>Conclusion</h3><div>Through the promotion of GABA_B levels, regulation of synaptic plasticity within the LHb, and inhibition of NF-κB/NLRP3-mediated neuroinflammation in the same region, electroacupuncture at <em>Shangxing</em> and <em>Fengfu</em> acupoints demonstrates efficacy in mitigating depression-like behaviors induced by CUMS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"218 ","pages":"Article 111108"},"PeriodicalIF":3.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased occurrence of microstate class B as the independent risk factor for persistent psychiatric symptoms related to omicron infection","authors":"Qinlian Huang ,&nbsp;Linqi Liu ,&nbsp;Lihong Huang ,&nbsp;Wei Zheng ,&nbsp;Yuping Zhao ,&nbsp;Kebin Zeng ,&nbsp;Fei Xiao ,&nbsp;Jing Luo ,&nbsp;Feng Li","doi":"10.1016/j.brainresbull.2024.111107","DOIUrl":"10.1016/j.brainresbull.2024.111107","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the EEG microstate characteristics in patients with persistent Omicron-related Psychiatric Symptoms (ORPS) as well as their correlations with the severity of ORPS.</div></div><div><h3>Methods</h3><div>This study included 31 patients with ORPS, and they were divided into remission group (n=19) and non-remission group (n=12) according to the decrease of Brief Psychiatric Rating Scale (BPRS) at discharge. Multivariate logistic models were applied to analyze the risk features associated with non-remission of ORPS at discharge, and the Spearman rank correlation was adopted to analyze the correlation between the occurrence of microstate class B and BPRS score at admission.</div></div><div><h3>Results</h3><div>The analysis revealed that an increased occurrence of EEG microstate class B was significantly associated with a higher likelihood of non-remission of ORPS at discharge (p &lt; 0.05). Furthermore, a moderate positive correlation was observed between the occurrence of microstate class B and BPRS scores at admission (r = 0.390, p = 0.030), indicating that patients with more frequent microstate class B tended to exhibit more severe psychiatric symptoms at onset.</div></div><div><h3>Conclusions</h3><div>The findings suggest that an increased occurrence of EEG microstate class B is an independent risk factor for non-remission of ORPS at discharge. Additionally, the positive correlation between microstate class B and BPRS scores underscores the potential of microstate class B as a biomarker for the severity of psychiatric symptoms in ORPS patients.</div></div><div><h3>Significance</h3><div>Identifying the increased occurrence of microstate class B at admission could serve as a novel marker for early assessment of ORPS severity and prognostic evaluation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"218 ","pages":"Article 111107"},"PeriodicalIF":3.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cedrol attenuates acute ischemic injury through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways","authors":"Yu Bi ,&nbsp;Ziyi Xie ,&nbsp;Xiang Cao ,&nbsp;Huanyu Ni ,&nbsp;Shengnan Xia ,&nbsp;Xinyu Bao ,&nbsp;Qinyue Huang ,&nbsp;Yun Xu ,&nbsp;Qingxiu Zhang","doi":"10.1016/j.brainresbull.2024.111102","DOIUrl":"10.1016/j.brainresbull.2024.111102","url":null,"abstract":"<div><div>Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"218 ","pages":"Article 111102"},"PeriodicalIF":3.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}