Neurotoxicology最新文献

{"title":"Synthetic cannabidiol analogues exhibit lower toxicity than cannabidiol and protect against ethanol-induced apoptosis in SH-SY5Y cells","authors":"Carolina Aparecida Faria Almeida ,&nbsp;Gabriela Salles ,&nbsp;Vitor Bruno ,&nbsp;Jessyca Milene Ribeiro ,&nbsp;Alessandra Oliveira Silva ,&nbsp;Giulia de Assis Braz ,&nbsp;Felype Valentim Duarte Castelhano ,&nbsp;Graziella dos Reis Rosa Franco ,&nbsp;Cláudio Viegas Jr. ,&nbsp;Tania Marcourakis ,&nbsp;Larissa Helena Lobo Torres ,&nbsp;Raphael Caio Tamborelli Garcia","doi":"10.1016/j.neuro.2026.103411","DOIUrl":"10.1016/j.neuro.2026.103411","url":null,"abstract":"<div><div>Cannabidiol (CBD) shows therapeutic potential for treating alcohol use disorder (AUD); however, its neurotoxicological profile remains insufficiently characterized, especially when compared with emerging synthetic analogues designed to improve safety. This study compares the neurotoxic and mechanistic profiles of CBD and two synthetic derivatives, PQM-242 and PQM-249, and evaluates their ability to attenuate ethanol-induced cellular injury. Human SH-SY5Y neuroblastoma cells were exposed to increasing concentrations (0.1–1000 µM) to generate concentration-response curves, estimate no-observed-adverse-effect levels (NOAELs), and determine cytotoxicity thresholds. Cell viability (MTT), apoptosis (annexin V/propidium iodide), and Bax and Bcl-2 expression (western blot) were assessed after 48 h of exposure. CBD showed an LC50 of 44 µM, whereas PQM-242 and PQM-249 displayed LC50 values &gt; 600 µM, indicating markedly lower intrinsic toxicity in the proposed study model. The NOAELs for PQM-242 and PQM-249 were 100 µM, compared with 10 µM for CBD. For co-exposure studies, 10 µM was selected to enable direct comparison under ethanol challenge (250 mM). All compounds reduced ethanol-induced loss of viability and apoptosis, and PQM-242 additionally prevented ethanol-mediated Bax upregulation. Overall, PQM-242 and PQM-249 demonstrated enhanced cellular safety and maintained protective activity, supporting their further investigation as candidate molecules for AUD.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103411"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged duration induces divergent transcriptomic responses to manganese, distinct from concentration effects, in an SH-SY5Y neurotoxicity model","authors":"Xueqi Tang ,&nbsp;Priyanka Baloni ,&nbsp;Michael Aschner ,&nbsp;Aaron B. Bowman","doi":"10.1016/j.neuro.2026.103393","DOIUrl":"10.1016/j.neuro.2026.103393","url":null,"abstract":"<div><div>Understanding manganese (Mn) neurotoxicity requires experimental models that realistically reflect human exposure scenarios. A key limitation of current <em>in vitro</em> paradigms is the reliance on acute, high-concentration exposures, which may not accurately capture the molecular consequences of long-term Mn accumulation. To address this, this study compared transcriptomic responses to acute (6-hour) and chronic (40-day) Mn exposures in SH-SY5Y cells, using Mn concentrations spanning near-physiological to sub-cytotoxic ranges. The 6-hour exposure design replicates a widely applied acute duration in the literature, while the 40-day duration was selected to mimic prolonged, low-level Mn burden reported in epidemiological and occupational studies. Bulk RNA sequencing revealed that chronic Mn exposure induced distinct and more extensive transcriptional alterations compared to acute exposure, independent of concentration. Pathway enrichment analyses indicated that cellular functions selectively perturbed under chronic conditions are highly relevant to neurodegenerative risks and aligns with independent Parkinson’s disease transcriptomic datasets. These pathways include axonal guidance signaling, amyloid fiber formation, extracellular matrix organization, and synaptic functioning. In contrast, acute exposures primarily disturbed intracellular ion homeostasis maintenance mechanisms. Protein kinase A signaling and metallothionein-mediated metal-binding pathway were the only two pathways that were shared between both applied durations exposed at Mn concentrations with reported adverse outcomes. Transcriptomic alterations in this study highlighted the contribution of mechanisms related to normal Mn-dependent cellular functions in the development of its neurotoxicity. Furthermore, these results emphasized that exposure duration is a critical determinant to be considered when evaluating long-term Mn overload-induced neurodegeneration via <em>in vitro</em> platforms.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103393"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From clinical observation to experimental validation: Investigating the neurotoxic impact of dimethylacetamide","authors":"Hizir Asliyuksek ,&nbsp;Nihan Hande Akcakaya ,&nbsp;Rumeysa Hekimoglu ,&nbsp;Simay Bozkurt ,&nbsp;Berna Yeniceri ,&nbsp;Onder Huseyinbas ,&nbsp;Sibel Atacan ,&nbsp;Mukaddes Esrefoglu ,&nbsp;Emrah Yucesan ,&nbsp;Beyza Goncu","doi":"10.1016/j.neuro.2026.103392","DOIUrl":"10.1016/j.neuro.2026.103392","url":null,"abstract":"<div><div>Dimethylacetamide (DMAC) is a polar organic solvent widely used in the production of synthetic fibers and other industrial applications. Its hepatotoxic potential has been well documented in laboratory animals and occupationally exposed workers, establishing DMAC as a recognized industrial hazard. However, evidence regarding its neurological effects remains scarce. We report a clinical case of accidental DMAC inhalation associated with diffuse cortical hyperintensity on brain magnetic resonance imaging, raising concern for direct neurotoxicity. To address this knowledge gap, we investigated the neurotoxic potential of DMAC in a controlled rat model experiment. Animals subjected to repeated intraperitoneal DMAC administration exhibited cortical and subcortical histopathological alterations consistent with neurotoxicity, accompanied by significant hepatic and renal injury. These findings provide the first experimental evidence that DMAC toxicity extends beyond hepatotoxicity to involve the central nervous system and kidneys, highlighting its potential for multi-organ toxicity and reinforcing concerns regarding occupational exposure risks.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103392"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia as a key mediator in rosuvastatin-associated cognitive impairment","authors":"Xianzheng Sang ,&nbsp;Yichao Ye ,&nbsp;Chengzi Yang ,&nbsp;Xiaoxiang Hou ,&nbsp;Yangu Guo ,&nbsp;Hantong Shi ,&nbsp;Chunhui Wang ,&nbsp;Wen Chen ,&nbsp;Danfeng Zhang ,&nbsp;Lijun Hou","doi":"10.1016/j.neuro.2026.103405","DOIUrl":"10.1016/j.neuro.2026.103405","url":null,"abstract":"<div><h3>Background</h3><div>Hydroxymethylglutaryl-coenzyme A (HMGCR) inhibitors, known as statins, as first-line lipid-lowering therapies for cardiovascular diseases. Despite their widespread use, concerns persist regarding potential cognitive adverse effects, although a definitive causal relationship remains elusive.</div></div><div><h3>Methods</h3><div>To investigate the underlying mechanisms, this study integrated network toxicology, in vitro experiments, public RNA-sequencing data, computational simulations, and Mendelian randomization analysis. Rosuvastatin was chosen as a representative statin, with human as the focused species and the HMC3 human microglial cell line as the <em>in vitro</em> model.</div></div><div><h3>Results</h3><div>Network toxicology initially identified microglia as a critically involved cell type. A multi-method approach then demonstrated that rosuvastatin alters microglial functions—including cell viability, migration, phagocytosis, and inflammatory responses—potentially by the JAK-STAT signaling pathway.</div></div><div><h3>Conclusions</h3><div>These findings suggest that rosuvastatin-induced disruption of microglial function may contribute to cognitive impairment. Our study elucidates potential pathways for this adverse effect and provides novel insights for developing preventive and therapeutic strategies.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103405"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taurine modulates gut microbiota and attenuates inflammation in a rotenone-induced mouse model of Parkinson's disease","authors":"Yunbo Zhu ,&nbsp;Shuo Wang ,&nbsp;Shuang Zhao ,&nbsp;Yujia Zeng ,&nbsp;Jing Li ,&nbsp;Pingyue Wang ,&nbsp;Zhijie Dou ,&nbsp;Tianjun Wang","doi":"10.1016/j.neuro.2026.103401","DOIUrl":"10.1016/j.neuro.2026.103401","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a prevalent neurodegenerative disorder in which gut microbiota play a critical role in pathogenesis through the gut–brain axis. Taurine has been reported to exhibit neuroprotective properties. In this study, we employed a rotenone-induced mouse model of PD to investigate the protective effects of taurine and elucidate its underlying mechanisms. PD model mice exhibited weight loss and impaired motor function, both of which were significantly ameliorated by taurine treatment. These mice also showed a marked reduction in dopaminergic neurons alongside increased microglial and astrocyte activation in the substantia nigra. Taurine preserved dopaminergic neuron numbers and suppressed glial activation. Elevated plasma levels of LPS, IL-1β, IL-6, and TNF-α were detected in the PD model group, accompanied by intestinal barrier dysfunction, blood–brain barrier disruption, and gastrointestinal impairment. Taurine administration significantly reduced pro-inflammatory cytokine levels, improved gastrointestinal motility, and preserved the integrity of both the intestinal and blood–brain barriers. Fecal microbiota analysis revealed significant compositional alterations in PD mice. Both α- and β-diversity analyses indicated profound microbial dysbiosis in the model group, which was effectively mitigated by taurine.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103401"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The long-acting anticoagulant rodenticide brodifacoum induces neuropathology in adult New Zealand White rabbits and is reduced by the bile sequestrant cholestyramine","authors":"Intakhar Ahmad ,&nbsp;Jacqueline Rocha ,&nbsp;Zachary McDonald ,&nbsp;Douglas L. Feinstein","doi":"10.1016/j.neuro.2026.103396","DOIUrl":"10.1016/j.neuro.2026.103396","url":null,"abstract":"<div><div>Previous studies showed that exposure to long-acting anticoagulant rodenticides (LAARs) can induce neuropathology in adult rats. In the current study we tested if the potent LAAR brodifacoum similarly promoted neuropathology in adult rabbits which provide a better model of human LAAR poisoning. Adult male New Zealand White rabbits were administered by gavage a single administration of brodifacoum at its LD₅₀ dose (200 μg/kg), followed by daily injections of vitamin K1 to prevent mortality due to anti-coagulation. After 3 weeks, examination of the cerebellum revealed an increase in glial cell activation, and a decrease in myelin content. A targeted lipidomics analysis was carried out to determine if brodifacoum altered the relative abundance of lipids enriched in myelin. We observed brodifacoum-dependent decreases in several sulfatides which were associated with an increase in expression of arylsulfatase A which degrades sulfatides. Daily treatment with the bile sequestrant cholestyramine, which accelerates LAAR clearance from the body, ameliorated brodifacoum -induced damage. These findings confirm that, despite daily vitamin K1 treatment, LAARs such as brodifacoum can induce neuropathology in adult animals and support the use of agents such as bile sequestrants to ameliorate those consequences.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103396"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking particulate matter exposure and neurological disorders: Evidence from epidemiology, biomarkers and mechanistic studies","authors":"Saiyami Bhardwaj ,&nbsp;Abhishek Bharti ,&nbsp;Radhey Shyam Sharma ,&nbsp;Santosh Kumar Mishra ,&nbsp;Pankaj Kumar ,&nbsp;Abdul S. Ethayathulla ,&nbsp;Atinderpal Singh ,&nbsp;Vandana Mishra","doi":"10.1016/j.neuro.2025.103375","DOIUrl":"10.1016/j.neuro.2025.103375","url":null,"abstract":"<div><div>Exposure to particulate matter (PM) including fine (PM₂.₅), coarse (PM₁₀), and ultrafine particles (UFPM) has emerged as a critical environmental determinant of neurological disorders, including Alzheimer’s and Parkinson’s diseases, neurodevelopmental impairments, and cognitive decline. This review integrates evidence from 129 research articles (2002–2025) to elucidate the mechanistic, biomarker-based, and public health dimensions of PM-induced neurotoxicity. Mechanistic pathways include oxidative stress, neuroinflammation, mitochondrial dysfunction, and blood–brain barrier disruption, with documented structural and functional damage in brain regions such as the hippocampus and prefrontal cortex. PM₂.₅ serves as a carrier of neurotoxic metals (e.g., lead, cadmium, vanadium) and understudied organic toxicants (e.g., PAHs, pesticides), amplifying its pathogenic potential. Exposure occurs through the olfactory route, systemic circulation, and gut–brain axis, highlighting multiple entry points into the central nervous system. Biomarkers such as Aβ₄₂, phosphorylated tau (p-tau), and α-synuclein are elevated in experimental models, but require greater validation in human PM-exposed populations. Children and older adults represent the most vulnerable groups due to developmental sensitivity and cumulative neuroinflammatory burden, yet remain underrepresented in cohort studies. Geographic disparities further limit generalizability, with low- and middle-income countries underrepresented despite experiencing the highest PM burdens. Future research must advance longitudinal, cohort and life-course studies, multi-omics biomarker discovery, and real-world mixture toxicology to identify intervention targets. These findings call for urgent integration of air pollution control into public health strategies targeting neurological diseases, emphasizing prevention through regulation, early detection, and equity-focused research frameworks.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103375"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomics reveals the mechanism of long-term neurodevelopmental toxicity following sevoflurane anesthesia","authors":"Jinnan Xu ,&nbsp;Ziyu Wang ,&nbsp;Hao Wang ,&nbsp;Hongbo Wen ,&nbsp;Zhirou Wen ,&nbsp;Longying Chen ,&nbsp;Yanyong Cheng ,&nbsp;Jia Yan ,&nbsp;Hong Jiang","doi":"10.1016/j.neuro.2026.103402","DOIUrl":"10.1016/j.neuro.2026.103402","url":null,"abstract":"<div><div>Prolonged exposure to general anesthetics during early development has been associated with neurobehavioral deficits. Sevoflurane, a commonly used pediatric anesthetic, may disrupt cortical maturation, particularly in the prefrontal cortex (PFC) which plays a critical integrative and regulatory role in cognitive and motor functions. In this study, the long-term effects of neonatal sevoflurane exposure were examined using a mouse model, complemented by analysis of single-cell RNA sequencing data from human embryonic PFC (GSE196239). Behavioral assays showed that mice exposed to sevoflurane at postnatal day 7 exhibited persistent impairments in fine motor ability and spatial memory in adulthood. Transcriptomic analysis showed that sevoflurane induced widespread gene expression alterations without changing the major cell-type composition. Through enrichment analysis, dysregulation of pathways related to cell shape was identified. Consistent with these transcriptomic findings, reduced dendritic complexity was observed in sevoflurane-treated neurons by immunofluorescence. Notably, microtubule-associated protein 2 (MAP2), a key structural protein in dendrites, was significantly reduced at the protein level without a corresponding decrease in mRNA expression, suggesting the involvement of post-transcriptional regulation. Together, these findings suggest that prolonged neonatal sevoflurane exposure may impair neuronal maturation and dendritic architecture, and provide molecular insights into the long-term cognitive and motor alterations associated with neonatal sevoflurane exposure.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103402"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sevoflurane aggravated neuroinflammation and oxidative stress in neonatal mice by modulating microglia phenotype via circRNA2092/miR-873a-5p/KEAP1","authors":"Yanan Li ,&nbsp;Juan Du ,&nbsp;Jiajie Zhang ,&nbsp;Zhenzhen Cai ,&nbsp;Lei Shi ,&nbsp;Jia Liang ,&nbsp;Qi Zhang","doi":"10.1016/j.neuro.2026.103410","DOIUrl":"10.1016/j.neuro.2026.103410","url":null,"abstract":"<div><div>Repeat sevoflurane exposure can cause developmental neurotoxicity while its underlying mechanism is still ambiguous. Contemporary research has increasingly highlighted the regulatory role of non-coding RNAs (ncRNAs) in the development of neurological diseases, particularly neurodegenerative conditions. However, the potential involvement of ncRNAs in sevoflurane-induced neurotoxicity remains poorly understood. In the current study, our comprehensive analysis of competing endogenous RNAs (ceRNAs) networks has identified circleRNA (circRNA) 2092 as a pivotal modulator in repetitive sevoflurane-mediated cognitive impairment, regulating microglia oxidative stress through the inhibition of microRNA miR-873a-5p and the promotion of Kelch-like ECH associating protein 1(KEAP1) expression. Notably, either knockdown of circRNA2092 and KEAP1 or administration of miR-873a-5p and Resveratrol (Oxidative stress inhibitor) could reverse the neurotoxicity of sevoflurane. Collectively, these findings demonstrate that repetitive sevoflurane exposure leads to long-term cognitive impairment in neonatal mice by aggravating microglial oxidative stress and neuroinflammatory response via the circRNA2092/miR-873a-5p/KEAP1 axis.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103410"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gallic and ascorbic acids either alone or combined contribute to ameliorating lead-induced cerebral neurotoxicity in rats: A histological and immunohistochemical study","authors":"Lamiaa M. Shawky ,&nbsp;Ahmed A. Morsi ,&nbsp;Nermine Beshara ,&nbsp;Omar T. Abualnasr ,&nbsp;Ghena Hamza ,&nbsp;Lamia Asali ,&nbsp;Faten Asali ,&nbsp;Eman El Bana","doi":"10.1016/j.neuro.2026.103395","DOIUrl":"10.1016/j.neuro.2026.103395","url":null,"abstract":"<div><div>Lead (Pb) toxicity is a great community health problem. Brain is the primary target organ of Pb intoxication. Ascorbic acid (AA) and Gallic acid (GA) have proven to show potential anti‑inflammatory and antioxidant properties during heavy metal intoxication. So, the current paper aimed to explore the possible protection of AA, GA, and their combination in the current model of Pb neurotoxicity. Fifty-six Wistar male albino rats were assigned into seven groups: control, AA alone (10 mg/kg, oral), GA alone (20 mg/kg, oral), Pb alone (40 mg/kg, intraperitoneal), AA/Pb, GA/Pb, and AA/GA/Pb combination groups. After one month of oral treatment, the animals were humanely killed, and brain cortical samples were extracted for biochemical measurement of the inflammatory and oxidative markers in the brain tissue homogenates. Moreover, the samples were subjected to structural and ultrastructural examinations using light and electron microscopic (EM) studies. Pb resulted in brain injury indicated by remarkable structural and ultrastructural changes evident by neuronal degeneration and reduction of healthy nerve cells. EM showed atrophic nerve cells with irregular outlines, swollen, rarefied mitochondria, and enlarged, fused electron-dense lysosomes indicating possible autophagic vacuoles. Also, a significant increase in the pro-inflammatory markers was noticed, as evident by the raised immunohistochemical expression of glial fibrillary acidic protein (GFAP), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α). In addition, the anti-inflammatory marker decreased, as denoted by the decline in superoxide dismutase (SOD) and catalase. All these alterations were lessened by AA and GA with great restoration in the AA/GA combination group, which showed almost normal histological, ultrastructural, and biochemical parameters. AA and GA are suggested to alleviate Pb‑induced neurotoxicity owing to the modulation of oxidative stress, inflammation, and apoptosis. However, the AA/GA combination shows the greatest effect as evidenced by biochemical, structural, and ultrastructural analyses.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"113 ","pages":"Article 103395"},"PeriodicalIF":3.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}