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The alteration to the nervous system that yields nicotine dependence further exacerbates the negative impact that nicotine use has on public health. Nicotine use has also been found to cause alterations in exosome content, especially miRNA. Conversely, exosomes have also had promising results as treatments for nicotine-mediated alterations in protein and miRNA levels. However, although nicotine has been shown to both alter exosome content and exacerbate stroke outcomes, the relationship between these two functions is poorly understood. This review examines multiple sources to compare available data. Several factors in nicotine\u2019s effect on exosome content were thus found that imply a correlation. Also, exosome contents are not only a viable biomarker for multiple conditions, including ischemic brain damage and tobacco use, but they are also able to influence the cells of test subjects, both as a treatment for ischemic stroke and as a regulator of healthy brain function in stroke-free test subjects. Taken together, previous evidence suggests that nicotine-mediated alterations in neuronal exosome content have an effect on the progression of stroke in nicotine users.<\/jats:p>","DOI":"10.3390\/biom16030463","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T08:54:37Z","timestamp":1773910477000},"page":"463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nicotine-Mediated Alterations in Exosome Content: Implications for Stroke and Neurological Dysfunction"],"prefix":"10.3390","volume":"16","author":[{"given":"Christopher","family":"Grahe","sequence":"first","affiliation":[{"name":"Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Egleton","sequence":"additional","affiliation":[{"name":"Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3343-6081","authenticated-orcid":false,"given":"Nalini","family":"Santanam","sequence":"additional","affiliation":[{"name":"Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2404-1782","authenticated-orcid":false,"given":"Ji Chen","family":"Bihl","sequence":"additional","affiliation":[{"name":"Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.bbagen.2012.03.017","article-title":"Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials","volume":"1820","author":"Vlassov","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alzahrani, F.A., Riza, Y.M., Eid, T.M., Almotairi, R., Scherschinski, L., Contreras, J., Nadeem, M., Perez, S.E., Raikwar, S.P., and Jha, R.M. (2024). Exosomes in Vascular\/Neurological Disorders and the Road Ahead. Cells, 13.","DOI":"10.3390\/cells13080670"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1139\/o92-028","article-title":"The Jeanne Manery-Fisher Memorial Lecture 1991. Maturation of reticulocytes: Formation of exosomes as a mechanism for shedding membrane proteins","volume":"70","author":"Johnstone","year":"1992","journal-title":"Biochem. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"447","DOI":"10.4161\/cib.3.5.12339","article-title":"Exosomes: Fit to deliver small RNA","volume":"3","author":"Zomer","year":"2010","journal-title":"Commun. Integr. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1038\/s41598-025-85373-9","article-title":"Altered expression profile of plasma exosomal microRNAs in exclusive electronic cigarette adult users","volume":"15","author":"Li","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kodidela, S., Gerth, K., Sinha, N., Kumar, A., Kumar, P., and Kumar, S. (2020). Circulatory Astrocyte and Neuronal EVs as Potential Biomarkers of Neurological Dysfunction in HIV-Infected Subjects and Alcohol\/Tobacco Users. Diagnostics, 10.","DOI":"10.3390\/diagnostics10060349"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"ENEURO.0166-16.2016","DOI":"10.1523\/ENEURO.0166-16.2016","article-title":"Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex","volume":"3","author":"Esterlis","year":"2016","journal-title":"eNeuro"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1152\/physrev.00014.2018","article-title":"The Neuroscience of Drug Reward and Addiction","volume":"99","author":"Volkow","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMra0809890","article-title":"Nicotine addiction","volume":"362","author":"Benowitz","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"81977","DOI":"10.18632\/oncotarget.13463","article-title":"Nicotine inside neurons","volume":"7","author":"Gotti","year":"2016","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4137\/JEN.S11381","article-title":"A role for matrix metalloproteinases in nicotine-induced conditioned place preference and relapse in adolescent female rats","volume":"7","author":"Natarajan","year":"2013","journal-title":"J. Exp. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Huang, L.Y., Song, J.X., Cai, H., Wang, P.P., Yin, Q.L., Zhang, Y.D., Chen, J., Li, M., Song, J.J., and Wang, Y.L. (2022). Healthy Serum-Derived Exosomes Improve Neurological Outcomes and Protect Blood-Brain Barrier by Inhibiting Endothelial Cell Apoptosis and Reversing Autophagy-Mediated Tight Junction Protein Reduction in Rat Stroke Model. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.841544"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1152\/physiol.00029.2013","article-title":"Matrix metalloproteinase-9: Many shades of function in cardiovascular disease","volume":"28","author":"Yabluchanskiy","year":"2013","journal-title":"Physiology"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Singh, K.P., Maremanda, K.P., Li, D., and Rahman, I. (2020). Exosomal microRNAs are novel circulating biomarkers in cigarette, waterpipe smokers, E-cigarette users and dual smokers. BMC Med. Genom., 13.","DOI":"10.1186\/s12920-020-00748-3"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kaur, G., Singh, K., Maremanda, K.P., Li, D., Chand, H.S., and Rahman, I. (2020). Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0243065"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Koul, S., Schaal, V.L., Chand, S., Pittenger, S.T., Nanoth Vellichirammal, N., Kumar, V., Guda, C., Bevins, R.A., Yelamanchili, S.V., and Pendyala, G. (2020). Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration. Cells, 9.","DOI":"10.3390\/cells9081883"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.atherosclerosis.2020.02.010","article-title":"Electronic cigarettes containing nicotine increase endothelial and platelet derived extracellular vesicles in healthy volunteers","volume":"301","author":"Mobarrez","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.drugalcdep.2019.04.011","article-title":"The rise of e-cigarettes, pod mod devices, and JUUL among youth: Factors influencing use, health implications, and downstream effects","volume":"201","author":"Fadus","year":"2019","journal-title":"Drug Alcohol Depend."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e38552","DOI":"10.1016\/j.heliyon.2024.e38552","article-title":"Single-cell RNA sequencing reveals heterogeneity of ALI model and epithelial cell alterations after exposure to electronic cigarette aerosol","volume":"10","author":"Cai","year":"2024","journal-title":"Heliyon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s40246-023-00504-5","article-title":"Smoking-related dysregulation of plasma circulating microRNAs: The Rotterdam study","volume":"17","author":"Maas","year":"2023","journal-title":"Hum. Genom."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ye, X., Luo, H., Chen, Y., Wu, Q., Xiong, Y., Zhu, J., Diao, Y., Wu, Z., Miao, J., and Wan, J. (2015). MicroRNAs 99b-5p\/100-5p Regulated by Endoplasmic Reticulum Stress are Involved in Abeta-Induced Pathologies. Front. Aging Neurosci., 7.","DOI":"10.3389\/fnagi.2015.00210"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e40677","DOI":"10.1097\/MD.0000000000040677","article-title":"Differential analysis of microRNAs in plasma exosomes in patients with cerebral ischemic stroke","volume":"103","author":"Lan","year":"2024","journal-title":"Medicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.toxrep.2020.09.001","article-title":"A meta-analysis of microRNAs expressed in human aerodigestive epithelial cultures and their role as potential biomarkers of exposure response to nicotine-containing products","volume":"7","author":"Sewer","year":"2020","journal-title":"Toxicol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"365","DOI":"10.2174\/1567202616666190906125444","article-title":"MiR-125a-5p Alleviates Dysfunction and Inflammation of Pentylenetetrazol- induced Epilepsy Through Targeting Calmodulin-dependent Protein Kinase IV (CAMK4)","volume":"16","author":"Liu","year":"2019","journal-title":"Curr. Neurovascular Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.ntt.2009.04.064","article-title":"Arsenic down-regulates the expression of Camk4, an important gene related to cerebellar LTD in mice","volume":"31","author":"Wang","year":"2009","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"C279","DOI":"10.1152\/ajpcell.00242.2025","article-title":"In vivo inhibition of miR-125b-5p modulates monocyte trafficking through the CCR7 receptor and reduces atherosclerosis","volume":"330","author":"Rotllan","year":"2026","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.nbd.2016.03.016","article-title":"Matrix metalloproteinase-13 participates in neuroprotection and neurorepair after cerebral ischemia in mice","volume":"91","author":"Ma","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.nbd.2006.12.008","article-title":"BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP\/PS1 transgenic mice","volume":"26","author":"Ohno","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e70025","DOI":"10.1002\/syn.70025","article-title":"miR-365a-3p Alleviates Isoflurane-Induced Neuroinflammation and Cognitive Impairment by Targeting MyD88 to Inhibit NF-\u03baB Signaling","volume":"79","author":"Bai","year":"2025","journal-title":"Synapse"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bbi.2020.09.024","article-title":"Abnormal brain structure and behavior in MyD88-deficient mice","volume":"91","author":"Schroeder","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111352","DOI":"10.1016\/j.mad.2020.111352","article-title":"Brazilian Aging Brain Study Group. Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer\u2019s disease","volume":"191","author":"Henriques","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hajny, S., and Christoffersen, C. (2017). A Novel Perspective on the ApoM-S1P Axis, Highlighting the Metabolism of ApoM and Its Role in Liver Fibrosis and Neuroinflammation. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081636"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41598-019-56089-4","article-title":"Association of relative brain age with tobacco smoking, alcohol consumption, and genetic variants","volume":"10","author":"Ning","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7118","DOI":"10.1007\/s12035-023-03518-1","article-title":"Exosomal circCNOT6L Regulates Astrocyte Apoptotic Signals Induced by Hypoxia Exposure Through miR99a-5p\/SERPINE1 and Alleviates Ischemic Stroke Injury","volume":"60","author":"He","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/ana.25965","article-title":"Circulating microRNAs Associated with Reversible Cerebral Vasoconstriction Syndrome","volume":"89","author":"Chen","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"134329","DOI":"10.1016\/j.ijbiomac.2024.134329","article-title":"An integrated bioinformatics approach reveals the potential role of microRNA-30b-5p and let-7a-5p during SARS CoV-2 spike-1 mediated neuroinflammation","volume":"277","author":"Pawar","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1007\/s11011-024-01395-8","article-title":"Exosomal MicroRNAs modulate the cognitive function in fasudil treated APPswe\/PSEN1dE9 transgenic (APP\/PS1) mice model of Alzheimer\u2019s disease","volume":"39","author":"Yan","year":"2024","journal-title":"Metab. Brain Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Brindley, E., Heiland, M., Mooney, C., Diviney, M., Mamad, O., Hill, T.D.M., Yan, Y., Ven\u00f8, M.T., Reschke, C.R., and Batool, A. (2023). Brain cell-specific origin of circulating microRNA biomarkers in experimental temporal lobe epilepsy. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1230942"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6901","DOI":"10.7150\/thno.37357","article-title":"Exosomes from nicotine-stimulated macrophages accelerate atherosclerosis through miR-21-3p\/PTEN-mediated VSMC migration and proliferation","volume":"9","author":"Zhu","year":"2019","journal-title":"Theranostics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4849","DOI":"10.1007\/s00018-021-03824-8","article-title":"Biogenesis, physiological functions and potential applications of extracellular vesicles in substance use disorders","volume":"78","author":"Chivero","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.freeradbiomed.2025.01.004","article-title":"E-cigarette-induced changes in cell stress and mitochondrial function","volume":"228","author":"Chitteti","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1161\/CIR.0000000000001123","article-title":"Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.4103\/NRR.NRR-D-23-02051","article-title":"Exosomes: The next-generation therapeutic platform for ischemic stroke","volume":"20","author":"Yin","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1161\/01.STR.0000196957.55928.ab","article-title":"Time is brain\u2014Quantified","volume":"37","author":"Saver","year":"2006","journal-title":"Stroke"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1007\/s00335-024-10052-5","article-title":"The expression profile of brain-derived exosomal miRNAs reveals the key molecules responsible for spontaneous motor function recovery in a rat model with permanent middle cerebral artery occlusion","volume":"35","author":"Liu","year":"2024","journal-title":"Mamm. Genome"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"106000","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.106000","article-title":"Comorbidity in Stroke-Survivors: Prevalence and Associations with Functional Outcomes and Health","volume":"30","author":"Appelros","year":"2021","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e9255","DOI":"10.1097\/MD.0000000000009255","article-title":"Cardiovascular risk factors in patients with combined central retinal vein occlusion and cilioretinal artery occlusion: Case report","volume":"97","author":"Grzybowski","year":"2018","journal-title":"Medicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1161\/STROKEAHA.123.046101","article-title":"Electronic Cigarette Vape Exposure Exacerbates Post-Ischemic Outcomes in Female but Not in Male Rats","volume":"55","author":"Pradhyumnan","year":"2024","journal-title":"Stroke"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"115416","DOI":"10.1016\/j.expneurol.2025.115416","article-title":"Exposure to electronic cigarette vapor exacerbates ischemic loss of tryptophan\/tyrosine hydroxylase-positive neurons in the rat brain","volume":"393","author":"Sanchez","year":"2025","journal-title":"Exp. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.redox.2017.06.006","article-title":"Offsetting the impact of smoking and e-cigarette vaping on the cerebrovascular system and stroke injury: Is Metformin a viable countermeasure?","volume":"13","author":"Kaisar","year":"2017","journal-title":"Redox Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12987-022-00371-7","article-title":"Short-term exposure to JUUL electronic cigarettes can worsen ischemic stroke outcome","volume":"19","author":"Sifat","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1093\/ntr\/ntae045","article-title":"Impact of Total Indoor Smoking Ban on Cardiovascular Disease Hospitalizations and Mortality: The Case of Chile","volume":"26","author":"Paraje","year":"2024","journal-title":"Nicotine Tob. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1097\/NRL.0000000000000474","article-title":"Acute Ischemic Stroke Among Cannabis Users in the United States and Possible Risk Factors for Mortality","volume":"28","author":"Ramphul","year":"2023","journal-title":"Neurologist"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1124\/jpet.109.157776","article-title":"Nicotine exacerbates brain edema during in vitro and in vivo focal ischemic conditions","volume":"332","author":"Paulson","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"d\u2019Adesky, N.D., de Rivero Vaccari, J.P., Bhattacharya, P., Schatz, M., Perez-Pinzon, M.A., Bramlett, H.M., and Raval, A.P. (2018). Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051330"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.neuroscience.2011.02.036","article-title":"Nicotine and estrogen synergistically exacerbate cerebral ischemic injury","volume":"181","author":"Raval","year":"2011","journal-title":"Neuroscience"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1152\/japplphysiol.00663.2015","article-title":"Chronic nicotine exposure exacerbates transient focal cerebral ischemia-induced brain injury","volume":"120","author":"Li","year":"2016","journal-title":"J. Appl. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7845","DOI":"10.1007\/s12035-024-04075-x","article-title":"M2 Microglia-Derived Exosomes Protect Against Glutamate-Induced HT22 Cell Injury via Exosomal miR-124-3p","volume":"61","author":"Zhu","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"112466","DOI":"10.1016\/j.intimp.2024.112466","article-title":"Exosome microRNA-125a-5p derived from epithelium promotes M1 macrophage polarization by targeting IL1RN in chronic obstructive pulmonary disease","volume":"137","author":"Wang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e12165","DOI":"10.1002\/jev2.12165","article-title":"Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors","volume":"10","author":"Mighty","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4103\/1673-5374.340406","article-title":"Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome","volume":"18","author":"Noh","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.4161\/auto.21561","article-title":"Immune-related GTPase M (IRGM1) regulates neuronal autophagy in a mouse model of stroke","volume":"8","author":"He","year":"2012","journal-title":"Autophagy"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.bbrc.2019.11.086","article-title":"Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression","volume":"522","author":"Xing","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"117337","DOI":"10.1016\/j.biopha.2024.117337","article-title":"\u03b17nACh receptor, a promising target to reduce BBB damage by regulating inflammation and autophagy after ischemic stroke","volume":"179","author":"Gao","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Patel, S.H., Tim\u00f3n-G\u00f3mez, A., Pradhyumnan, H., Mankaliye, B., Dave, K.R., Perez-Pinzon, M.A., and Raval, A.P. (2022). The Impact of Nicotine along with Oral Contraceptive Exposure on Brain Fatty Acid Metabolism in Female Rats. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232416075"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1177\/0271678X20925164","article-title":"Simultaneous nicotine and oral contraceptive exposure alters brain energy metabolism and exacerbates ischemic stroke injury in female rats","volume":"41","author":"Diaz","year":"2021","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s12975-020-00854-5","article-title":"Nicotine Exposure Along with Oral Contraceptive Treatment in Female Rats Exacerbates Post-cerebral Ischemic Hypoperfusion Potentially via Altered Histamine Metabolism","volume":"12","author":"Diaz","year":"2021","journal-title":"Transl. Stroke Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/jnc.14561","article-title":"Nicotine and electronic cigarette (E-Cig) exposure decreases brain glucose utilization in ischemic stroke","volume":"147","author":"Sifat","year":"2018","journal-title":"J. Neurochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12987-015-0005-y","article-title":"Nicotine pre-exposure reduces stroke-induced glucose transporter-1 activity at the blood-brain barrier in mice","volume":"12","author":"Shah","year":"2015","journal-title":"Fluids Barriers CNS"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"113424","DOI":"10.1016\/j.celrep.2023.113424","article-title":"Prostate cancer cell-derived exosomal IL-8 fosters immune evasion by disturbing glucolipid metabolism of CD8+ T cell","volume":"42","author":"Xu","year":"2023","journal-title":"Cell Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.bpsgos.2023.08.019","article-title":"The Role of Microglia in Sex- and Region-Specific Blood-Brain Barrier Integrity During Nicotine Withdrawal","volume":"4","author":"Kumar","year":"2023","journal-title":"Biol. Psychiatry Glob. Open Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.bbi.2020.03.034","article-title":"Electronic cigarette exposure disrupts blood-brain barrier integrity and promotes neuroinflammation","volume":"88","author":"Heldt","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"H353","DOI":"10.1152\/ajpheart.00979.2020","article-title":"Soluble epoxide hydrolase deletion attenuated nicotine-induced arterial stiffness via limiting the loss of SIRT1","volume":"321","author":"Hu","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Naik, P., Sajja, R.K., Prasad, S., and Cucullo, L. (2015). Effect of full flavor and denicotinized cigarettes exposure on the brain microvascular endothelium: A microarray-based gene expression study using a human immortalized BBB endothelial cell line. BMC Neurosci., 16.","DOI":"10.1186\/s12868-015-0173-3"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1093\/ntr\/ntx020","article-title":"VISTA Collaborators Searching for the Smoker\u2019s Paradox in Acute Stroke Patients Treated with Intravenous Thrombolysis","volume":"19","author":"Hussein","year":"2017","journal-title":"Nicotine Tob. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1093\/ntr\/ntz094","article-title":"Meta-analysis of the Smoker\u2019s Paradox in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis or Endovascular Treatment","volume":"21","author":"Zhang","year":"2019","journal-title":"Nicotine Tob. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"155290","DOI":"10.1016\/j.prp.2024.155290","article-title":"Investigation of smoking on the antiplatelet response to clopidogrel: Unravelling the smoker\u2019s paradox","volume":"257","author":"Plakogiannis","year":"2024","journal-title":"Pathol. Res. Pract."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3325\/cmj.2019.60.439","article-title":"Adipose-derived mesenchymal stem cells attenuate ischemic brain injuries in rats by modulating miR-21-3p\/MAT2B signaling transduction","volume":"60","author":"Li","year":"2019","journal-title":"Croat. Med. J."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Fei, S., Xu, M., Liu, Z., Xie, H., Yu, Y., Chu, Y., Zhu, L., Fang, Z., Jin, Y., and Yao, Y. (2025). Molecular epidemiological study of exosomes circZNF609, circPUM1, IGF2 with ischemic stroke. BMC Cardiovasc. Disord., 25.","DOI":"10.1186\/s12872-025-04663-2"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"\u015aniadach, J., Kicman, A., Michalska-Falkowska, A., Jo\u0144czyk, K., and Waszkiewicz, N. (2025). Changes in Concentration of Selected Biomarkers of Exposure in Users of Classic Cigarettes, E-Cigarettes, and Heated Tobacco Products-A Narrative Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26051796"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Zhao, B., Wu, J., Han, M., Rong, X., Jin, J., Liu, S., Zhang, C., Zhang, R., Chen, X., and Peng, F. (2025). Exosome-related genes influence the progression of stroke through neuroinflammatory responses. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1517588"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"H563","DOI":"10.1152\/ajpheart.00042.2013","article-title":"Nicotine potentiates proatherogenic effects of oxLDL by stimulating and upregulating macrophage CD36 signaling","volume":"305","author":"Zhou","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"28223","DOI":"10.1038\/s41598-024-79558-x","article-title":"Hippocampal exosomes from stroke aggravate post-stroke depression by regulating the expression of proBDNF and p75NTR and altering spine density","volume":"14","author":"Huang","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"46","DOI":"10.4103\/ijpvm.ijpvm_41_23","article-title":"Preventive Effects of Crocin, a Key Carotenoid Component in Saffron, Against Nicotine-Triggered Neurodegeneration in Rat Hippocampus: Possible Role of Autophagy and Apoptosis","volume":"15","author":"Gholami","year":"2024","journal-title":"Int. J. Prev. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Alasmari, F., Alotibi, F.M., Alqahtani, F., Alshammari, T.K., Kadi, A.A., Alghamdi, A.M., Allahem, B.S., Alasmari, A.F., Alsharari, S.D., and Al-Rejaie, S.S. (2022). Effects of Chronic Inhalation of Electronic Cigarette Vapor Containing Nicotine on Neurobehaviors and Pre\/Postsynaptic Neuron Markers. Toxics, 10.","DOI":"10.3390\/toxics10060338"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Zhou, L., Tao, X., Pang, G., Mu, M., Sun, Q., Liu, F., Hu, Y., Tao, H., Li, B., and Xu, K. (2021). Maternal Nicotine Exposure Alters Hippocampal Microglia Polarization and Promotes Anti-inflammatory Signaling in Juvenile Offspring in Mice. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.661304"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1586\/erc.10.56","article-title":"Smoking and stroke: The more you smoke the more you stroke","volume":"8","author":"Shah","year":"2010","journal-title":"Expert. Rev. Cardiovasc. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1176\/appi.ajp.2015.15030363","article-title":"Post-Stroke Depression: A Review","volume":"173","author":"Robinson","year":"2016","journal-title":"Am. J. Psychiatry"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Sewell, L., and Cray, J.J. (2025). Nicotine alters cellular activity and mRNA expression of patterns of Astrocytes. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0325529"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.lfs.2010.06.012","article-title":"Neonatal nicotine exposure alters leptin signaling in the hypothalamus-pituitary-thyroid axis in the late postnatal period and adulthood in rats","volume":"87","author":"Moura","year":"2010","journal-title":"Life Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"116079","DOI":"10.1016\/j.ecoenv.2024.116079","article-title":"Maternal nicotine exposure promotes hippocampal CeRNA-mediated excitotoxicity and social barriers in adolescent offspring mice","volume":"273","author":"Zhao","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"156160","DOI":"10.1016\/j.metabol.2025.156160","article-title":"Neuroprotective effect of small extracellular vesicle-mediated targeting of AMPK\u03b12 in cerebral ischemia","volume":"167","author":"Ouro","year":"2025","journal-title":"Metabolism"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"9363390","DOI":"10.1155\/jimr\/9363390","article-title":"Plasma-Derived Neuronal Exosomal CircRNAs as Potential Biomarkers for Central Nervous System Infections","volume":"2025","author":"Zhang","year":"2025","journal-title":"J. Immunol. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1021\/acs.nanolett.8b04148","article-title":"Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neurodevelopmental Disorders","volume":"19","author":"Perets","year":"2019","journal-title":"Nano Lett."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s41467-018-03733-8","article-title":"Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson\u2019s disease treatment","volume":"9","author":"Kojima","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e3933","DOI":"10.7717\/peerj.3933","article-title":"The neuroprotective effect of nicotine in Parkinson\u2019s disease models is associated with inhibiting PARP-1 and caspase-3 cleavage","volume":"5","author":"Lu","year":"2017","journal-title":"PeerJ"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1080\/15384101.2020.1731649","article-title":"Astrocyte-derived exosomes transfer miR-190b to inhibit oxygen and glucose deprivation-induced autophagy and neuronal apoptosis","volume":"19","author":"Pei","year":"2020","journal-title":"Cell Cycle"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1161\/STROKEAHA.119.028012","article-title":"Mesenchymal stromal cell-derived small extracellular vesicles induce ischemic neuroprotection by modulating leukocytes and specifically neutrophils","volume":"51","author":"Wang","year":"2020","journal-title":"Stroke"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1161\/STROKEAHA.121.035821","article-title":"Postischemic neuroprotection associated with anti-inflammatory effects by mesenchymal stromal cell-derived small extracellular vesicles in aged mice","volume":"53","author":"Wang","year":"2022","journal-title":"Stroke"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e70055","DOI":"10.1002\/jsp2.70055","article-title":"Analysis of Nicotine Toxicity and Mechanisms of Senescence in Nucleus Pulposus Cells Using Network Toxicology and Molecular Docking Technique","volume":"8","author":"Jiang","year":"2025","journal-title":"JOR Spine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1002\/ppul.21099","article-title":"Combined effects of chronic nicotine and acute virus exposure on neurotrophin expression in rat lung","volume":"44","author":"Urrego","year":"2009","journal-title":"Pediatr. Pulmonol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.bcp.2019.08.003","article-title":"Developmental nicotine exposure elicits multigenerational disequilibria in proBDNF proteolysis and glucocorticoid signaling in the frontal cortices, striata, and hippocampi of adolescent mice","volume":"168","author":"Buck","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"H1518","DOI":"10.1152\/ajpheart.00928.2010","article-title":"Nicotine aggravates the brain postischemic inflammatory response","volume":"300","author":"Bradford","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jconrel.2015.03.033","article-title":"Exosomes as drug delivery vehicles for Parkinson\u2019s disease therapy","volume":"207","author":"Haney","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"102140","DOI":"10.1016\/j.isci.2021.102140","article-title":"Conserved nicotine-activated neuroprotective pathways involve mitochondrial stress","volume":"24","author":"Nourse","year":"2021","journal-title":"iScience"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1248\/bpb.32.332","article-title":"Nicotinic receptor-mediated neuroprotection in neurodegenerative disease models","volume":"32","author":"Shimohama","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"10781","DOI":"10.1074\/jbc.M500084200","article-title":"Nicotine inactivation of the proapoptotic function of Bax through phosphorylation","volume":"280","author":"Xin","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"112831","DOI":"10.1016\/j.ecoenv.2021.112831","article-title":"Decreased mitochondrial DNA copy number in nerve cells and the hippocampus during nicotine exposure is mediated by autophagy","volume":"226","author":"Wang","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1186\/s12967-025-06283-y","article-title":"Human neural stem cell-derived exosomes activate PINK1\/Parkin pathway to protect against oxidative stress-induced neuronal injury in ischemic stroke","volume":"23","author":"Zhao","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Ullah, I., Zhao, L., Uddin, S., Zhou, Y., Wang, X., and Li, H. (2024). Nicotine-mediated therapy for Parkinson\u2019s disease in transgenic Caenorhabditis elegans model. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1358141"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/cei.13388","article-title":"Nicotine modulates molecules of the innate immune response in epithelial cells and macrophages during infection with M. tuberculosis","volume":"199","year":"2020","journal-title":"Clin. Exp. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Meng, T.T., Wang, W., Meng, F.L., Wang, S.Y., Wu, H.H., Chen, J.M., Zheng, Y., Wang, G.X., Zhang, M.X., and Li, Y. (2021). Nicotine Causes Mitochondrial Dynamics Imbalance and Apoptosis Through ROS Mediated Mitophagy Impairment in Cardiomyocytes. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.650055"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e150249","DOI":"10.1172\/jci.insight.150249","article-title":"The miR-182-5p\/FGF21\/acetylcholine axis mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis","volume":"6","author":"Meng","year":"2021","journal-title":"JCI Insight"},{"key":"ref_114","first-page":"5319","article-title":"Inhibition of human breast cancer metastasis in nude mice by synthetic glycoamines","volume":"56","author":"Glinsky","year":"1996","journal-title":"Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"107908","DOI":"10.1016\/j.phrs.2025.107908","article-title":"Exosome-mediated microglia-astrocyte interactions drive neuroinflammation in Parkinson\u2019s disease with Peli1 as a potential therapeutic target","volume":"219","author":"Guo","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"4351","DOI":"10.7150\/thno.52436","article-title":"Ultrasound-mediated augmented exosome release from astrocytes alleviates amyloid-\u03b2-induced neurotoxicity","volume":"11","author":"Deng","year":"2021","journal-title":"Theranostics"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12974-020-01761-0","article-title":"Astrocyte-derived exosomes enriched with miR-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury","volume":"17","author":"Long","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/s41419-022-05454-9","article-title":"Astrocyte-derived exosomal nicotinamide phosphoribosyltransferase (Nampt) ameliorates ischemic stroke injury by targeting AMPK\/mTOR signaling to induce autophagy","volume":"13","author":"Deng","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e12433","DOI":"10.1002\/jev2.12433","article-title":"Extracellular vesicles as human therapeutics: A scoping review of the literature","volume":"13","author":"Fusco","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1016\/j.ymthe.2024.06.025","article-title":"Prospects and challenges of tissue-derived extracellular vesicles","volume":"32","author":"Lee","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.7150\/ijbs.79461","article-title":"Brain-derived extracellular vesicles promote bone-fat imbalance in Alzheimer\u2019s disease","volume":"19","author":"Liu","year":"2023","journal-title":"Int. J. Biol. Sci."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/3\/463\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:17:58Z","timestamp":1774070278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/3\/463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,19]]},"references-count":121,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["biom16030463"],"URL":"https:\/\/doi.org\/10.3390\/biom16030463","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,19]]}}}