Bioelectronic medicine最新文献

{"title":"Hepatic stellate cell activation markers are regulated by the vagus nerve in systemic inflammation.","authors":"Osman Ahmed,&nbsp;April S Caravaca,&nbsp;Maria Crespo,&nbsp;Wanmin Dai,&nbsp;Ting Liu,&nbsp;Qi Guo,&nbsp;Magdalena Leiva,&nbsp;Guadalupe Sabio,&nbsp;Vladimir S Shavva,&nbsp;Stephen G Malin,&nbsp;Peder S Olofsson","doi":"10.1186/s42234-023-00108-3","DOIUrl":"https://doi.org/10.1186/s42234-023-00108-3","url":null,"abstract":"<p><strong>Background: </strong>The liver is an important immunological organ and liver inflammation is part of the pathophysiology of non-alcoholic steatohepatitis, a condition that may promote cirrhosis, liver cancer, liver failure, and cardiovascular disease. Despite dense innervation of the liver parenchyma, little is known about neural regulation of liver function in inflammation. Here, we study vagus nerve control of the liver response to acute inflammation.</p><p><strong>Methods: </strong>Male C57BL/6 J mice were subjected to either sham surgery, surgical vagotomy, or electrical vagus nerve stimulation followed by intraperitoneal injection of the TLR2 agonist zymosan. Animals were euthanized and tissues collected 12 h after injection. Samples were analyzed by qPCR, RNAseq, flow cytometry, or ELISA.</p><p><strong>Results: </strong>Hepatic mRNA levels of pro-inflammatory mediators Ccl2, Il-1β, and Tnf-α were significantly higher in vagotomized mice compared with mice subjected to sham surgery. Differences in liver Ccl2 levels between treatment groups were largely reflected in the plasma chemokine (C-C motif) ligand 2 (CCL2) concentration. In line with this, we observed a higher number of macrophages in the livers of vagotomized mice compared with sham as measured by flow cytometry. In mice subjected to electrical vagus nerve stimulation, hepatic mRNA levels of Ccl2, Il1β, and Tnf-α, and plasma CCL2 levels, were significantly lower compared with sham. Interestingly, RNAseq revealed that a key activation marker for hepatic stellate cells (HSC), Pnpla3, was the most significantly differentially expressed gene between vagotomized and sham mice. Of note, several HSC-activation associated transcripts were higher in vagotomized mice, suggesting that signals in the vagus nerve contribute to HSC activation. In support of this, we observed significantly higher number of activated HSCs in vagotomized mice as compared with sham as measured by flow cytometry.</p><p><strong>Conclusions: </strong>Signals in the cervical vagus nerve controlled hepatic inflammation and markers of HSC activation in zymosan-induced peritonitis.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"9 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9288194","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":"Brief periods of transcutaneous auricular vagus nerve stimulation improve autonomic balance and alter circulating monocytes and endothelial cells in patients with metabolic syndrome: a pilot study.","authors":"Tercio Lemos de Moraes, Fernando Oliveira Costa, Danielly Gomes Cabral, Daniella Marques Fernandes, Carine Teles Sangaleti, Maria Aparecida Dalboni, Josiane Motta E Motta, Liliane Appratto de Souza, Nicola Montano, Maria Claudia Irigoyen, Michael Brines, Kevin J Tracey, Valentin A Pavlov, Fernanda M Consolim Colombo","doi":"10.1186/s42234-023-00109-2","DOIUrl":"10.1186/s42234-023-00109-2","url":null,"abstract":"<p><strong>Background: </strong>There is emerging evidence that the nervous system regulates immune and metabolic alterations mediating Metabolic syndrome (MetS) pathogenesis via the vagus nerve. This study evaluated the effects of transcutaneous auricular vagus nerve stimulation (TAVNS) on key cardiovascular and inflammatory components of MetS.</p><p><strong>Methods: </strong>We conducted an open label, randomized (2:1), two-arm, parallel-group controlled trial in MetS patients. Subjects in the treatment group (n = 20) received 30 min of TAVNS with a NEMOS® device placed on the cymba conchae of the left ear, once weekly. Patients in the control group (n = 10) received no stimulation. Hemodynamic, heart rate variability (HRV), biochemical parameters, and monocytes, progenitor endothelial cells, circulating endothelial cells, and endothelial micro particles were evaluated at randomization, after the first TAVNS treatment, and again after 8 weeks of follow-up.</p><p><strong>Results: </strong>An improvement in sympathovagal balance (HRV analysis) was observed after the first TAVNS session. Only patients treated with TAVNS for 8 weeks had a significant decrease in office BP and HR, a further improvement in sympathovagal balance, with a shift of circulating monocytes towards an anti-inflammatory phenotype and endothelial cells to a reparative vascular profile.</p><p><strong>Conclusion: </strong>These results are of interest for further study of TAVNS as treatment of MetS.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"9 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9227296","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":"The Fifth Bioelectronic Medicine Summit Hosted by the Feinstein Institutes for Medical Research (Manhasset, NY) and Columbia Engineering (NY, NY) at The Garden City Hotel, Garden City, NY 11530 on October 11-12^th, 2002- Bioelectronic Medicine: Today's Tools, Tomorrow's Therapies : Sponsored by IRIS Biomedical, Neuromodec, Bioelectronic Medicine (journal), and Feinstein Institutes for Medical Research/Northwell Health.","authors":"","doi":"10.1186/s42234-023-00105-6","DOIUrl":"https://doi.org/10.1186/s42234-023-00105-6","url":null,"abstract":"","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"9 Suppl 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2023-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9116203","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":"Characterization and applications of evoked responses during epidural electrical stimulation.","authors":"Nishant Verma, Ben Romanauski, Danny Lam, Luis Lujan, Stephan Blanz, Kip Ludwig, Scott Lempka, Andrew Shoffstall, Bruce Knudson, Yuichiro Nishiyama, Jian Hao, Hyun-Joo Park, Erika Ross, Igor Lavrov, Mingming Zhang","doi":"10.1186/s42234-023-00106-5","DOIUrl":"10.1186/s42234-023-00106-5","url":null,"abstract":"<p><strong>Background: </strong>Epidural electrical stimulation (EES) of the spinal cord has been FDA approved and used therapeutically for decades. However, there is still not a clear understanding of the local neural substrates and consequently the mechanism of action responsible for the therapeutic effects.</p><p><strong>Method: </strong>Epidural spinal recordings (ESR) are collected from the electrodes placed in the epidural space. ESR contains multi-modality signal components such as the evoked neural response (due to tonic or BurstDR™ waveforms), evoked muscle response, stimulation artifact, and cardiac response. The tonic stimulation evoked compound action potential (ECAP) is one of the components in ESR and has been proposed recently to measure the accumulative local potentials from large populations of neuronal fibers during EES.</p><p><strong>Result: </strong>Here, we first review and investigate the referencing strategies, as they apply to ECAP component in ESR in the domestic swine animal model. We then examine how ECAP component can be used to sense lead migration, an adverse outcome following lead placement that can reduce therapeutic efficacy. Lastly, we show and isolate concurrent activation of local back and leg muscles during EES, demonstrating that the ESR obtained from the recording contacts contain both ECAP and EMG components.</p><p><strong>Conclusion: </strong>These findings may further guide the implementation of recording and reference contacts in an implantable EES system and provide preliminary evidence for the utility of ECAP component in ESR to detect lead migration. We expect these results to facilitate future development of EES methodology and implementation of use of different components in ESR to improve EES therapy.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"9 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9976490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9771984","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":"Measuring and modeling the effects of vagus nerve stimulation on heart rate and laryngeal muscles.","authors":"William J Huffman, Eric D Musselman, Nicole A Pelot, Warren M Grill","doi":"10.1186/s42234-023-00107-4","DOIUrl":"10.1186/s42234-023-00107-4","url":null,"abstract":"<p><strong>Background: </strong>Reduced heart rate (HR) during vagus nerve stimulation (VNS) is associated with therapy for heart failure, but stimulation frequency and amplitude are limited by patient tolerance. An understanding of physiological responses to parameter adjustments would allow differential control of therapeutic and side effects. To investigate selective modulation of the physiological responses to VNS, we quantified the effects and interactions of parameter selection on two physiological outcomes: one related to therapy (reduced HR) and one related to side effects (laryngeal muscle EMG).</p><p><strong>Methods: </strong>We applied a broad range of stimulation parameters (mean pulse rates (MPR), intra-burst frequencies, and amplitudes) to the vagus nerve of anesthetized mice. We leveraged the in vivo recordings to parameterize and validate computational models of HR and laryngeal muscle activity across amplitudes and temporal patterns of VNS. We constructed a finite element model of excitation of fibers within the mouse cervical vagus nerve.</p><p><strong>Results: </strong>HR decreased with increased amplitude, increased MPR, and decreased intra-burst frequency. EMG increased with increased MPR. Preferential HR effects over laryngeal EMG effects required combined adjustments of amplitude and MPR. The model of HR responses highlighted contributions of ganglionic filtering to VNS-evoked changes in HR at high stimulation frequencies. Overlap in activation thresholds between small and large modeled fibers was consistent with the overlap in dynamic ranges of related physiological measures (HR and EMG).</p><p><strong>Conclusion: </strong>The present study provides insights into physiological responses to VNS required for informed parameter adjustment to modulate selectively therapeutic effects and side effects.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"9 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9237256","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":"Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?","authors":"Marco Leitzke","doi":"10.1186/s42234-023-00104-7","DOIUrl":"10.1186/s42234-023-00104-7","url":null,"abstract":"<p><p>Following a SARS-CoV-2 infection, many individuals suffer from post-COVID-19 syndrome. It makes them unable to proceed with common everyday activities due to weakness, memory lapses, pain, dyspnea and other unspecific physical complaints. Several investigators could demonstrate that the SARS-CoV-2 related spike glycoprotein (SGP) attaches not only to ACE-2 receptors but also shows DNA sections highly affine to nicotinic acetylcholine receptors (nAChRs). The nAChR is the principal structure of cholinergic neuromodulation and is responsible for coordinated neuronal network interaction. Non-intrinsic viral nAChR attachment compromises integrative interneuronal communication substantially. This explains the cognitive, neuromuscular and mood impairment, as well as the vegetative symptoms, characterizing post-COVID-19 syndrome. The agonist ligand nicotine shows an up to 30-fold higher affinity to nACHRs than acetylcholine (ACh). We therefore hypothesize that this molecule could displace the virus from nAChR attachment and pave the way for unimpaired cholinergic signal transmission. Treating several individuals suffering from post-COVID-19 syndrome with a nicotine patch application, we witnessed improvements ranging from immediate and substantial to complete remission in a matter of days.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"9 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10604123","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":"A radiographic, deep transfer learning framework, adapted to estimate lung opacities from chest x-rays.","authors":"Avantika Vardhan,&nbsp;Alex Makhnevich,&nbsp;Pravan Omprakash,&nbsp;David Hirschorn,&nbsp;Matthew Barish,&nbsp;Stuart L Cohen,&nbsp;Theodoros P Zanos","doi":"10.1186/s42234-022-00103-0","DOIUrl":"https://doi.org/10.1186/s42234-022-00103-0","url":null,"abstract":"<p><p>Chest radiographs (CXRs) are the most widely available radiographic imaging modality used to detect respiratory diseases that result in lung opacities. CXR reports often use non-standardized language that result in subjective, qualitative, and non-reproducible opacity estimates. Our goal was to develop a robust deep transfer learning framework and adapt it to estimate the degree of lung opacity from CXRs. Following CXR data selection based on exclusion criteria, segmentation schemes were used for ROI (Region Of Interest) extraction, and all combinations of segmentation, data balancing, and classification methods were tested to pick the top performing models. Multifold cross validation was used to determine the best model from the initial selected top models, based on appropriate performance metrics, as well as a novel Macro-Averaged Heatmap Concordance Score (MA HCS). Performance of the best model is compared against that of expert physician annotators, and heatmaps were produced. Finally, model performance sensitivity analysis across patient populations of interest was performed. The proposed framework was adapted to the specific use case of estimation of degree of CXR lung opacity using ordinal multiclass classification. Acquired between March 24, 2020, and May 22, 2020, 38,365 prospectively annotated CXRs from 17,418 patients were used. We tested three neural network architectures (ResNet-50, VGG-16, and ChexNet), three segmentation schemes (no segmentation, lung segmentation, and lateral segmentation based on spine detection), and three data balancing strategies (undersampling, double-stage sampling, and synthetic minority oversampling) using 38,079 CXR images for training, and validation with 286 images as the out-of-the-box dataset that underwent expert radiologist adjudication. Based on the results of these experiments, the ResNet-50 model with undersampling and no ROI segmentation is recommended for lung opacity classification, based on optimal values for the MAE metric and HCS (Heatmap Concordance Score). The degree of agreement between the opacity scores predicted by this model with respect to the two sets of radiologist scores (OR or Original Reader and OOBTR or Out Of Box Reader) in terms of performance metrics is superior to the inter-radiologist opacity score agreement.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"9 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2023-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9809517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10545554","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":"Sympathetic innervation of human and porcine spleens: implications for between species variation in function.","authors":"Logan G Kirkland,&nbsp;Chloe G Garbe,&nbsp;Joseph Hadaya,&nbsp;Paul V Benson,&nbsp;Brant M Wagener,&nbsp;Sanjin Tankovic,&nbsp;Donald B Hoover","doi":"10.1186/s42234-022-00102-1","DOIUrl":"https://doi.org/10.1186/s42234-022-00102-1","url":null,"abstract":"<p><strong>Background: </strong>The vagus nerve affects innate immune responses by activating spleen-projecting sympathetic neurons, which modulate leukocyte function. Recent basic and clinical research investigating vagus nerve stimulation to engage the cholinergic anti-inflammatory pathway (CAP) has shown promising therapeutic results for a variety of inflammatory diseases. Abundant sympathetic innervation occurs in rodent spleens, and use of these species has dominated mechanistic research investigating the CAP. However, previous neuroanatomical studies of human spleen found a more restricted pattern of innervation compared to rodents. Therefore, our primary goal was to establish the full extent of sympathetic innervation of human spleens using donor tissue with the shortest procurement to fixation time. Parallel studies of porcine spleen, a large animal model, were performed as a positive control and for comparison.</p><p><strong>Methods: </strong>Human and porcine spleen tissue were fixed immediately after harvest and prepared for immunohistochemistry. Human heart and porcine spleen were stained in conjunction as positive controls. Several immunohistochemical protocols were compared for best results. Tissue was stained for tyrosine hydroxylase (TH), a noradrenergic marker, using VIP purple chromogen. Consecutive tissue slices were stained for neuropeptide Y (NPY), which often co-localizes with TH, or double-labelled for TH and CD3, a T cell marker. High-magnification images and full scans of the tissue were obtained and analyzed for qualitative differences between species.</p><p><strong>Results: </strong>TH had dominant perivascular localization in human spleen, with negligible innervation of parenchyma, but such nerves were abundant throughout ventricular myocardium. In marked contrast, noradrenergic innervation was abundant in all regions of porcine spleen, with red pulp having more nerves than white pulp. NPY stain results were consistent with this pattern. In human spleen, noradrenergic nerves only ran close to T cells at the boundary of the periarterial lymphatic sheath and arteries. In porcine spleen, noradrenergic nerves were closely associated with T cells in both white and red pulp as well as other leukocytes in red pulp.</p><p><strong>Conclusion: </strong>Sympathetic innervation of the spleen varies between species in both distribution and abundance, with humans and pigs being at opposite extremes. This has important implications for sympathetic regulation of neuroimmune interactions in the spleen of different species and focused targeting of the CAP in humans.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"8 1","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2022-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9748306","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":"Vagus nerve stimulation and inflammation: expanding the scope beyond cytokines.","authors":"Aidan Falvey","doi":"10.1186/s42234-022-00100-3","DOIUrl":"https://doi.org/10.1186/s42234-022-00100-3","url":null,"abstract":"<p><p>Approximately 20 years ago it was discovered that the vagus nerve regulates pro-inflammatory cytokine levels and inflammation. Subsequent research using several preclinical models revealed that vagus nerve stimulation evokes a protective decrease in pro-inflammatory cytokines in multiple inflammatory disorders. Consequently, the pro- and anti- inflammatory cytokine balance has become the predominant readout for indicating a positive outcome of vagus nerve stimulation. However, cytokine levels are just a single aspect of an effective immune response. It is conceivable that vagus nerve stimulation regulates inflammation through additional mechanisms. In this letter, I discuss a manuscript that describes how vagus nerve stimulation promotes resolution of inflammation via regulating the balance of specialised pro-resolving mediator levels and neutrophil activity.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"8 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10321203","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":"A dual tracer [¹¹C]PBR28 and [¹⁸F]FDG microPET evaluation of neuroinflammation and brain energy metabolism in murine endotoxemia.","authors":"Santhoshi P Palandira, Joseph Carrion, Lauren Turecki, Aidan Falvey, Qiong Zeng, Hui Liu, Tea Tsaava, Dov Herschberg, Michael Brines, Sangeeta S Chavan, Eric H Chang, An Vo, Yilong Ma, Christine N Metz, Yousef Al-Abed, Kevin J Tracey, Valentin A Pavlov","doi":"10.1186/s42234-022-00101-2","DOIUrl":"10.1186/s42234-022-00101-2","url":null,"abstract":"<p><strong>Background: </strong>Brain metabolic alterations and neuroinflammation have been reported in several peripheral inflammatory conditions and present significant potential for targeting with new diagnostic approaches and treatments. However, non-invasive evaluation of these alterations remains a challenge.</p><p><strong>Methods: </strong>Here, we studied the utility of a micro positron emission tomography (microPET) dual tracer ([¹¹C]PBR28 - for microglial activation and [¹⁸F]FDG for energy metabolism) approach to assess brain dysfunction, including neuroinflammation in murine endotoxemia. MicroPET imaging data were subjected to advanced conjunction and individual analyses, followed by post-hoc analysis.</p><p><strong>Results: </strong>There were significant increases in [¹¹C]PBR28 and [¹⁸F]FDG uptake in the hippocampus of C57BL/6 J mice 6 h following LPS (2 mg/kg) intraperitoneal (i.p.) administration compared with saline administration. These results confirmed previous postmortem observations. In addition, patterns of significant simultaneous activation were demonstrated in the hippocampus, the thalamus, and the hypothalamus in parallel with other tracer-specific and region-specific alterations. These changes were observed in the presence of robust systemic inflammatory responses manifested by significantly increased serum cytokine levels.</p><p><strong>Conclusions: </strong>Together, these findings demonstrate the applicability of [¹¹C]PBR28 - [¹⁸F]FDG dual tracer microPET imaging for assessing neuroinflammation and brain metabolic alterations in conditions \"classically\" characterized by peripheral inflammatory and metabolic pathogenesis.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"8 1","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163013","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}