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The BBB is a specialized neurovascular unit composed of endothelial tight junctions, pericytes, astrocytes, and basement membrane structures that undergo coordinated molecular and cellular changes during ischemia\u2013reperfusion injury, generating diverse biomarker signatures including endothelial dysfunction, oxidative stress, inflammatory mediators, and extracellular matrix remodeling. However, conventional biomarkers and imaging approaches fail to fully capture the dynamic and heterogeneous nature of BBB injury. Meaningful interpretation of BBB\u2010derived biomarkers requires mechanistic understanding of their molecular and cellular origins, making the integration of BBB pathophysiology with computational modeling essential for clinically relevant translation. Recent advances in machine learning (ML) and deep learning (DL) enable integration of neuroimaging, molecular, clinical, and multi\u2010omics data to characterize BBB dysfunction and improve prediction of stroke outcomes. ML\u2010based models have demonstrated value in identifying BBB\u2010related signatures associated with infarct progression, hemorrhagic transformation, and functional recovery, while deep neural networks enhance lesion segmentation and prognostic modeling. Despite this progress, challenges including data heterogeneity, limited longitudinal datasets, and model interpretability remain barriers to clinical translation. This review integrates the molecular and cellular mechanisms of BBB disruption with machine learning approaches for BBB biomarker profiling, highlighting a pathway toward biologically informed, personalized ischemic stroke management.<\/jats:p>","DOI":"10.14814\/phy2.71003","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:59:48Z","timestamp":1783083588000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms and integrative machine learning approaches to blood\u2013brain barrier biomarker profiling for personalized ischemic stroke management"],"prefix":"10.14814","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9687-2113","authenticated-orcid":false,"given":"John","family":"Nzobokela","sequence":"first","affiliation":[{"name":"Department of Pathology Ndola Teaching Hospital  Ndola Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2808-0319","authenticated-orcid":false,"given":"Lweendo","family":"Muchaili","sequence":"additional","affiliation":[{"name":"HAND Research Group, School of Medicine and Health Sciences Mulungushi University  Livingstone Zambia"},{"name":"Department of Cardiovascular Science and Metabolic Diseases Livingstone Center for Prevention and Translational Science  Livingstone Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy Kaluba","family":"Mangimela","sequence":"additional","affiliation":[{"name":"Department of Pathology Ndola Teaching Hospital  Ndola Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-9359","authenticated-orcid":false,"given":"Annet","family":"Kirabo","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Vanderbilt Institute for Global Health Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Vanderbilt Center for Immunobiology Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Vanderbilt Institute for Infection, Immunology and Inflammation Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4376-5831","authenticated-orcid":false,"given":"Sepiso K.","family":"Masenga","sequence":"additional","affiliation":[{"name":"HAND Research Group, School of Medicine and Health Sciences Mulungushi University  Livingstone Zambia"},{"name":"Department of Cardiovascular Science and Metabolic Diseases Livingstone Center for Prevention and Translational Science  Livingstone Zambia"},{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Vanderbilt Institute for Global Health Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00095.2018"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1668420"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1499493"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02912-9"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02888-6"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26052364"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102362"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.594672"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2025.109063"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.036946"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.08.043"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13121647"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pdig.0000033"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252010891"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.382228"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25158404"},{"key":"e_1_2_12_18_1","unstructured":"Delgrange C. 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