Xiaoxi Zhao, Yi Yang, Xiangying Du, Luguang Li, Chengbei Hou, Yanning Cai, Xin Ma
{"title":"Dependence of mitochondrial dysfunction in peripheral blood mononuclear cells on cervicocephalic atherosclerotic burden in acute ischemic stroke.","authors":"Xiaoxi Zhao, Yi Yang, Xiangying Du, Luguang Li, Chengbei Hou, Yanning Cai, Xin Ma","doi":"10.3389/ebm.2025.10624","DOIUrl":"https://doi.org/10.3389/ebm.2025.10624","url":null,"abstract":"<p><p>As an inflammatory disease, atherosclerosis is associated with acute ischemic stroke (AIS), but its early identification and intervention efficacy remain suboptimal. A new research direction may be to explore peripheral atherosclerotic biomarkers from the perspective of mitochondrial dysfunction, which can induce inflammatory cell activation. Moreover, the degree of overall cervicocephalic atherosclerosis (namely, atherosclerotic burden) is more closely related to AIS prognosis than local atherosclerotic lesions. Therefore, this study investigated the relationship between mitochondrial dysfunction in peripheral blood mononuclear cells (PBMCs), including monocytes and lymphocytes, and overall cervicocephalic atherosclerotic burden and AIS outcome. Patients with AIS and cervicocephalic atherosclerosis were enrolled and followed up for 90 days. The reactive oxygen species (ROS) and the mitochondrial deoxyribonucleic acid copy number (mtDNA-CN) in PBMCs were measured respectively through a fluorescence probe and a droplet digital polymerase chain reaction to evaluate mitochondrial function. The overall intracranial and cervical atherosclerotic burden (ICAB) was quantified by summing up the atherosclerosis degree points in each arterial segment as assessed by computed tomography angiography. A modified Rankin Scale (mRS) score >2 was considered a 90-day unfavorable functional outcome. Five (4.9%) of the 103 patients with AIS were lost to follow-up. mtDNA-CN [adjusted β = -0.099, 95% confidence intervals (CIs) = -0.153 ∼ -0.044, <i>p</i> < 0.001] and ROS content (adjusted β = 1.275, 95%CI = 0.885 ∼ 1.665, <i>p</i> < 0.001) were correlated with ICAB. The risk of a 90-day unfavorable functional outcome increased with higher ROS content [adjusted odds ratio (OR) = 1.523, 95%CI = 1.172 ∼ 1.981, <i>p</i> = 0.002] and decreased with higher mtDNA-CN (adjusted OR = 0.911, 95%CI = 0.850 ∼ 0.976, <i>p</i> = 0.008). PBMC mitochondrial dysfunction was found to be independently associated with extensive and severe cervicocephalic atherosclerosis and a 90-day unfavorable functional outcome in patients with AIS, which may provide a novel approach to improving the early identification and risk stratification of cervicocephalic atherosclerosis, along with the prediction of the outcome of atherosclerotic AIS.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10624"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms for reducing/eliminating chronic neuropathic pain with a focus on platelet-rich plasma.","authors":"Damien P Kuffler, Christian A Foy","doi":"10.3389/ebm.2025.10567","DOIUrl":"10.3389/ebm.2025.10567","url":null,"abstract":"<p><p>Peripheral nerve trauma commonly results in chronic neuropathic pain by up-regulating the synthesis and release of pro-inflammatory mediators from local and invading cells and inducing hyperexcitability of nociceptive neurons and spontaneous electrical activity. The pain decreases when these cells down-regulate genes supporting the pro-inflammatory state, up-regulate genes for expressing anti-inflammatory factors, and modulate genes that reduce nociceptive neuron spontaneous electrical activity. Pharmacological agents, the primary technique for reducing pain, do not eliminate pain, and <50% of patients achieve benefits because they do not address the underlying causes of pain. Alternative techniques providing longer lasting, but not complete or long-term pain relief include surgical interventions, electrical stimulation, and antibody treatment. Anti-inflammatory mediators can reduce pain, but the effect is not complete or long-lasting. Platelet-rich plasma (PRP) contains a readably available evolutionarily developed cocktail of factors that induce longer-lasting and more significant, but not complete, pain relief than other techniques. However, a novel study shows that unique formulations of PRP can induce long-term pain elimination. This review examines (1) the efficacy of drugs, regenerative peripheral nerve interface (RPNI), targeted muscle reinnervation (TMR), and PRP in reducing chronic neuropathic pain, (2) recent clinical data showing that a novel PRP application technique induces long-term chronic neuropathic pain reduction/elimination, and (3) discusses why the novel PRP may be more effective in reducing/eliminating chronic neuropathic pain.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10567"},"PeriodicalIF":2.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Experimental Biology and medicine conference thematic issue introduction.","authors":"Warren Zimmer","doi":"10.3389/ebm.2025.10698","DOIUrl":"10.3389/ebm.2025.10698","url":null,"abstract":"","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10698"},"PeriodicalIF":2.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Realizing Impact of Artificial Intelligence in Real World Enhances Public Health.","authors":"Huixiao Hong, William Slikker","doi":"10.3389/ebm.2025.10700","DOIUrl":"10.3389/ebm.2025.10700","url":null,"abstract":"","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10700"},"PeriodicalIF":2.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cheng Wang, Jinchun Sun, Rohini Donakonda, Richard Beger, Leah E Latham, Leihong Wu, Shuliang Liu, Joseph P Hanig, Fang Liu
{"title":"Assessing the developmental effects of fentanyl and impacts on lipidomic profiling using neural stem cell models.","authors":"Cheng Wang, Jinchun Sun, Rohini Donakonda, Richard Beger, Leah E Latham, Leihong Wu, Shuliang Liu, Joseph P Hanig, Fang Liu","doi":"10.3389/ebm.2025.10607","DOIUrl":"10.3389/ebm.2025.10607","url":null,"abstract":"<p><p>Fentanyl is a potent and short-acting opioid that is often given to pediatric patients during surgery to relieve pain and as an adjunct to anesthesia. Its effects on the developing brain are yet to be determined. In the present study, commercially available human neural stem cells (NSCs) were used to model the effects of fentanyl on the developing human brain. We determined the dose dependent effects and temporal relationships between fentanyl exposures and NSC health, viability, and differentiation. Markers of mitochondrial health [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT)] and cell death/damage [lactate dehydrogenase (LDH)] were monitored to determine the dose response effects of fentanyl on NSC viability. In addition, lipidomics analysis was conducted to investigate lipid profile changes in differentiated neural cells treated with fentanyl. Fentanyl did not cause a significant increase in LDH release, nor MTT reduction after 24-h exposure at concentrations of 0.5, 1.0, 3.0, 10, or 100 μM, for both NSCs and differentiated neural cells. Lipidomics data showed the top 15 most variable important in projection (VIP) lipid species (the higher the VIP scores, the bigger changes in treated groups vs. controls), including lysophosphatidylcholines (LPCs), lysophosphatidylethanolamines (LPEs), ceramides (CER), cholesterol esters (ChEs) and sphingosine (SPH). The lipidomic data indicate that LPC (16:0), LPC (16:1), LPC (18:1), CER (d18:0_22:0), CER (d18:2_18:0), CER(d18:2_24:1) were significantly increased, and only ChE (24:5) and SPH (d18:1) were significantly decreased in the highest dose group versus control. These data indicated that fentanyl exposure (24-h) did not induce detectable cell death. However, a lipidomic analysis indicated that fentanyl may affect immature neural cell functions through modifying lipid composition and lipid metabolism. These data indicated that despite the absence of clear neurodegeneration, fentanyl may still have a negative impact on the developing brain.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10607"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peace Asuzu, Naser Aliye Feto, Jim Wan, Frankie Stentz, Nawajes Mandal, Samuel Dagogo-Jack
{"title":"Selective association of plasma sphingolipid species with insulin sensitivity and secretion in normoglycemic Black and White American adults.","authors":"Peace Asuzu, Naser Aliye Feto, Jim Wan, Frankie Stentz, Nawajes Mandal, Samuel Dagogo-Jack","doi":"10.3389/ebm.2025.10538","DOIUrl":"10.3389/ebm.2025.10538","url":null,"abstract":"<p><p>Ceramides and other sphingolipids are associated with diabetes risk. Here, we examined the association of plasma sphingolipids with insulin sensitivity and secretion in people without diabetes. We enrolled adults without diabetes based on 75-g oral glucose tolerance test. Assessments included clinical examination, insulin sensitivity (hyperinsulinemic euglycemic clamp), and insulin secretion (intravenous glucose tolerance test). Plasma levels of 58 sphingolipid species (including ceramides, monohexosylceramides, sphingomyelins, and sphingosine) were assayed using liquid chromatography tandem mass spectrometry. The study participants (N = 240; 129 Black, 111 White) had a mean age of 43.1 ± 12.0 y, body mass index (BMI) 29.4 ± 6.23 kg/m<sup>2</sup>, fasting plasma glucose 91.4 ± 6.91 mg/dL, and 2-h plasma glucose 123 ± 26.3 mg/dL. Several of the 58 SPLs species assayed showed variable associations with insulin sensitivity (r = 0.17-0.35, P = 0.039 - <0.0001) and secretion (r = 0.14-0.27; P = 0.038 - <0.0001). After correction for multiple testing, plasma levels of very-long-chain (VLC) monohexosylceramide C34:0 (r = 0.31 - 0.43, P < 0.0001) and VLC sphingomyelins C28-C34 (r = 0.31-0.35, P = 0.0004 - <0.0001) were significantly associated with insulin sensitivity. Plasma VLC sphingomyelin level were inversely associated with insulin secretion, plasma glucose, BMI, and waist circumference. We conclude that circulating VLC sphingomyelins are associated positively with insulin action and inversely with insulin secretion and adiposity in normoglycemic adults, indicating a possible link to glucoregulation that precedes the development of dysglycemia.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10538"},"PeriodicalIF":2.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Winkens, Pauline Schweitzer, Olga Perkas, Christian Kühnel, Ferdinand Ndum, Marta Pomraenke, Julia Greiser, Martin Freesmeyer
{"title":"In-ovo imaging using ostrich eggs: biodistribution of F-18-FDG in ostrich embryos.","authors":"Thomas Winkens, Pauline Schweitzer, Olga Perkas, Christian Kühnel, Ferdinand Ndum, Marta Pomraenke, Julia Greiser, Martin Freesmeyer","doi":"10.3389/ebm.2025.10560","DOIUrl":"10.3389/ebm.2025.10560","url":null,"abstract":"<p><p>In-ovo imaging using ostrich eggs has been described as an alternative to animal testing using rodents. This approach is not considered an animal experiment and it does not require small-animal imaging devices as ostrich eggs provide good image quality on regular CT, MRI or PET used in humans. The aims of this study were 1) to describe methods of radiopharmaceutical injection, 2) to explore normal biodistribution of F-18-FDG during a 60-min list-mode-PET/CT examination and 3) to compare biodistribution in-ovo to existing literature considering chicken and rodents. Vessel access was successful in 54/78 ostrich eggs. Highest FDG-uptake was observed in epiphyseal plates (0.36 ± 0.06 IA%/g; range 0.29-0.48 IA%/g) and brain (0.25 ± 0.05 IA%/g; range 0.21-0.36 IA%/g). <i>In-vivo</i> activity distribution on PET and <i>ex-vivo</i> activity distribution (well counter) showed comparable results (Spearman's Rho range 0.795-0.882). No significant differences were observed regarding previous isoflurane exposure. Normal biodistribution of F-18-FDG in ostrich embryos using a standard PET/CT system for humans was mainly found as expected with highest uptake in epiphyseal plates and brain which is comparable to results on rodents and chicken embryos. Isoflurane anesthesia did not reveal significant differences regarding organ uptake. The results of this normal distribution study allow for interpretation of future disease models (inflammation, tumor) in ostrich embryos using F-18-FDG as radiopharmaceutical.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10560"},"PeriodicalIF":2.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaojing Du, Xiaohui Li, Sheng Yue, Yuzhen Sun, Mengzhen Zhao, Lingshan Zhou, Xingwei Wang, Yapan Yang
{"title":"Correlation study of CAR, PLR, NLR with the prognosis of cardiogenic cerebral embolism patients.","authors":"Xiaojing Du, Xiaohui Li, Sheng Yue, Yuzhen Sun, Mengzhen Zhao, Lingshan Zhou, Xingwei Wang, Yapan Yang","doi":"10.3389/ebm.2025.10517","DOIUrl":"10.3389/ebm.2025.10517","url":null,"abstract":"<p><p>This study explored the association between inflammatory biomarkers-C-reactive protein to albumin ratio (CAR), platelet to lymphocyte ratio (PLR), and neutrophil to lymphocyte ratio (NLR)-and the prognosis of patients with cardiogenic cerebral embolism (CCE). We retrospectively analyzed data from 80 CCE patients diagnosed between June 2020 and June 2024, categorizing them into favorable and unfavorable prognosis groups based on outcomes such as death, recurrence, and disability. The CAR, PLR, and NLR values were calculated from routine blood tests, and statistical analyses, including Spearman correlation, multivariate logistic regression, and ROC curve analysis, were performed to examine their prognostic significance. Results showed that the unfavorable prognosis group had significantly higher CAR, PLR, and NLR values compared to the favorable group (P < 0.05). Spearman correlation analysis revealed positive associations between these biomarkers and prognosis (r = 0.319 for CAR, 0.238 for PLR, 0.251 for NLR, all P < 0.05). Multivariate analysis identified CAR and NLR as independent risk factors for unfavorable prognosis (OR = 1.034 for CAR, OR = 3.887 for NLR). ROC analysis determined optimal cutoff values for CAR (>0.74), PLR (>160.00), and NLR (>3.53) to predict unfavorable prognosis with AUCs of 0.796, 0.694, and 0.705, respectively. The combined biomarker test yielded an AUC of 0.899. Kaplan-Meier survival analysis indicated significantly lower survival rates for patients with higher levels of CAR, PLR, and NLR (P < 0.05). In conclusion, elevated CAR, PLR, and NLR are reliable indicators of a poor prognosis in CCE patients.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10517"},"PeriodicalIF":2.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leah E Latham, Qiang Gu, Shuliang Liu, Cheng Wang, Fang Liu
{"title":"The effects of cannabidiol and its main metabolites on human neural stem cells.","authors":"Leah E Latham, Qiang Gu, Shuliang Liu, Cheng Wang, Fang Liu","doi":"10.3389/ebm.2025.10608","DOIUrl":"10.3389/ebm.2025.10608","url":null,"abstract":"<p><p>Cannabidiol (CBD) has been used for different purposes by different populations in recent years. When consumed by pregnant women, CBD can pass through the placenta and enter the fetal blood stream. There is concern over adverse effects of fetal exposure to CBD and its major metabolites (7-OH-CBD and 7-COOH-CBD). In the present study, human neural stem cells (NSCs) were treated with CBD and its metabolites at different concentrations for various durations to understand how the drug may affect fetal brain development. NSCs were also treated with delta-9 tetrahydrocannabinol (THC) for comparison purposes. CBD, 7-OH-CBD and 7-COOH-CBD dose-dependently reduced NSC viability. CBD and 7-OH-CBD reduced NSC number at the G1 phase. A 24 h exposure did not cause significant change in NSC proliferation. At concentrations comparable to those detected in human blood, longer exposures to CBD, 7-OH-CBD and 7-COOH-CBD caused more obvious cell death. After NSCs differentiation, CBD treatment reduced GFAP and cannabinoid receptor 2 (CB2) expression. THC treatment reduced the GFAP expression, but the change in CB2 expression did not reach statistical significance. The expression of cannabinoid receptor 1 (CB1) and beta-tubulin III were not significantly altered by drug exposures. The study demonstrated that clinically relevant concentrations of CBD, 7-OH-CBD and 7-COOH-CBD affect basic physiological features of human NSCs. After NSC differentiation, the reduced expression of CB2 receptors and GFAP on differentiated cells further indicated the vulnerability of developing central nervous system to CBD and THC. These data will help to contextualize <i>in vivo</i> neurodevelopmental studies that may not accurately model human metabolite profiles of CBD.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10608"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cheng Wang, Leah E Latham, Shuliang Liu, John Talpos, Tucker A Patterson, Joseph P Hanig, Fang Liu
{"title":"Assessing potential desflurane-induced neurotoxicity using nonhuman primate neural stem cell models.","authors":"Cheng Wang, Leah E Latham, Shuliang Liu, John Talpos, Tucker A Patterson, Joseph P Hanig, Fang Liu","doi":"10.3389/ebm.2025.10606","DOIUrl":"10.3389/ebm.2025.10606","url":null,"abstract":"<p><p>Safety concerns about general anesthetics (GA), such as desflurane (a commonly used gaseous anesthetic agent), arose from studies documenting neural cell death and behavioral changes after early-life exposure to anesthetics and compounds with related modes of action. Neural stem cells (NSCs) can recapitulate most critical events during central nervous system (CNS) development <i>in vivo</i> and, therefore, represent a valuable <i>in vitro</i> model for evaluating potential desflurane-induced developmental neurotoxicity. In this study, NSCs harvested from the hippocampus of a gestational day 80 monkey brain were applied to explore the temporal relationships between desflurane exposures and neural stem cell health, proliferation, differentiation, and viability. At clinically relevant doses (5.7%), desflurane exposure did not result in significant changes in NSC viability [lactate dehydrogenase (LDH) release] and NSC proliferation profile/rate by Cell Cycle Assay, in both short term (3 h) and prolonged (24 h) exposure groups. However, when monkey NSCs were guided to differentiate into neural cells (including neurons, astrocytes, and oligodendrocytes), and then exposed to desflurane (5.7%), no significant changes were detected in LDH release after a 3-h exposure, but a significant elevation in LDH release into the culture medium was observed after a 24-h exposure. Desflurane (24 h)-induced neural damage was further supported by increased expression levels of multiple cytokines, e.g., G-CSF, IL-12, IL-9, IL-10, and TNF-α compared with the controls. Additionally, our immunocytochemistry and flow cytometry data demonstrated a remarkable attenuation of differentiated neurons as evidenced by significantly decreased numbers of polysialic acid neural cell adhesion molecule (PSA-NCAM)-positive cells in the desflurane-exposed (prolonged) cultures. Our data suggests that at the clinically relevant concentration, desflurane did not induce NSC damage/death, but impaired the differentiated neuronal cells after prolonged exposure. Collectively, PSA-NCAM could be essential for neuronal viability. Desflurane-induced neurotoxicity was primarily associated with the loss of differentiated neurons. Changes in the neuronal specific marker, PSA-NCAM, may help understand the underlying mechanisms associated with anesthetic-induced neuronal damage. These findings should be helpful/useful for the understanding of the diverse effects of desflurane exposure on the developing brain and could be used to optimize the usage of these agents in the pediatric setting.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10606"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}