{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:31:28Z","timestamp":1790299888303,"version":"4.1.0"},"reference-count":107,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,25]],"date-time":"2023-03-25T00:00:00Z","timestamp":1679702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institutes of Health\/National Institute","doi-asserted-by":"publisher","award":["2R01-DA029121"],"award-info":[{"award-number":["2R01-DA029121"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institutes of Health\/National Institute","doi-asserted-by":"publisher","award":["1R01-DA049737"],"award-info":[{"award-number":["1R01-DA049737"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institutes of Health\/National Institute","doi-asserted-by":"publisher","award":["1R01-NS117906"],"award-info":[{"award-number":["1R01-NS117906"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders","doi-asserted-by":"publisher","award":["2R01-DA029121"],"award-info":[{"award-number":["2R01-DA029121"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders","doi-asserted-by":"publisher","award":["1R01-DA049737"],"award-info":[{"award-number":["1R01-DA049737"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders","doi-asserted-by":"publisher","award":["1R01-NS117906"],"award-info":[{"award-number":["1R01-NS117906"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic Brain Injury (TBI) is a primary cause of cerebrovascular and neurological disorders worldwide. The current scientific researchers believe that premorbid conditions such as tobacco smoking (TS) can exacerbate post-TBI brain injury and negatively affect recovery. This is related to vascular endothelial dysfunction resulting from the exposure to TS-released reactive oxygen species (ROS), nicotine, and oxidative stress (OS) stimuli impacting the blood\u2013brain barrier (BBB) endothelium. Interestingly, these pathogenic modulators of BBB impairment are similar to those associated with hyperglycemia. Antidiabetic drugs such as metformin (MF) and rosiglitazone (RSG) were shown to prevent\/reduce BBB damage promoted by chronic TS exposure. Thus, using in vivo approaches, we evaluated the effectiveness of post-TBI treatment with MF or RSG to reduce the TS-enhancement of BBB damage and brain injury after TBI. For this purpose, we employed an in vivo weight-drop TBI model using male C57BL\/6J mice chronically exposed to TS with and without post-traumatic treatment with MF or RSG. Our results revealed that these antidiabetic drugs counteracted TS-promoted downregulation of nuclear factor erythroid 2-related factor 2 (NRF2) expression and concomitantly dampened TS-enhanced OS, inflammation, and loss of BBB integrity following TBI. In conclusion, our findings suggest that MF and RSG could reduce the harmful impact of chronic smoking on post-traumatic brain injuries.<\/jats:p>","DOI":"10.3390\/ijms24076219","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T04:05:40Z","timestamp":1679889940000},"page":"6219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antidiabetic Drugs Can Reduce the Harmful Impact of Chronic Smoking on Post-Traumatic Brain Injuries"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8649-3712","authenticated-orcid":false,"given":"Farzane","family":"Sivandzade","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA"},{"name":"Department of Foundation Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3924-593X","authenticated-orcid":false,"given":"Faleh","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4120-4910","authenticated-orcid":false,"given":"Hemangini","family":"Dhaibar","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Cruz-Topete","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2827-7162","authenticated-orcid":false,"given":"Luca","family":"Cucullo","sequence":"additional","affiliation":[{"name":"Department of Foundation Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/s41582-018-0091-y","article-title":"Traumatic brain injury: Sex, gender and intersecting vulnerabilities","volume":"14","author":"Mollayeva","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1015791","DOI":"10.1155\/2022\/1015791","article-title":"Targeting Nrf2-Mediated Oxidative Stress Response in Traumatic Brain Injury: Therapeutic Perspectives of Phytochemicals","volume":"2022","author":"Wu","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Qin, D., Wang, J., Le, A., Wang, T.J., Chen, X., and Wang, J. (2021). Traumatic Brain Injury: Ultrastructural Features in Neuronal Ferroptosis, Glial Cell Activation and Polarization, and Blood\u2013Brain Barrier Breakdown. Cells, 10.","DOI":"10.3390\/cells10051009"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Janak, J., Pugh, M., and Orman, J. (2015). Epidemiology of traumatic brain injury. Trauma. Brain Inj. Rehabil. Med., 6\u201335.","DOI":"10.2217\/fmeb2013.13.296"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113987","DOI":"10.1016\/j.expneurol.2022.113987","article-title":"Mitoquinone supplementation alleviates oxidative stress and pathologic outcomes following repetitive mild traumatic brain injury at a chronic time point","volume":"351","author":"Tabet","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4438","DOI":"10.1007\/s12035-020-02040-y","article-title":"Glia maturation factor (GMF) regulates microglial expression phenotypes and the associated neurological deficits in a mouse model of traumatic brain injury","volume":"57","author":"Ahmed","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s13311-020-00840-7","article-title":"Cell death and recovery in traumatic brain injury","volume":"17","author":"Akamatsu","year":"2020","journal-title":"Neurotherapeutics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1089\/neu.2019.6932","article-title":"Neuroinflammation mediated by glia maturation factor exacerbates neuronal injury in an in vitro model of traumatic brain injury","volume":"37","author":"Ahmed","year":"2020","journal-title":"J. Neurotrauma"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1111\/ejn.14390","article-title":"Vascular and non-vascular contributors to memory reduction during traumatic brain injury","volume":"50","author":"Charkviani","year":"2019","journal-title":"Eur. J. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1177\/1073858419848293","article-title":"Brain injury\u2013mediated neuroinflammatory response and Alzheimer\u2019s disease","volume":"26","author":"Kempuraj","year":"2020","journal-title":"Neuroscientist"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1007\/s10571-020-00937-9","article-title":"Real-time noninvasive bioluminescence, ultrasound and photoacoustic imaging in NF\u03baB-RE-Luc transgenic mice reveal glia maturation factor-mediated immediate and sustained spatio-temporal activation of NF\u03baB signaling post-traumatic brain injury in a gender-specific manner","volume":"41","author":"Raikwar","year":"2021","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"230","DOI":"10.5607\/en20017","article-title":"Absence of glia maturation factor protects from axonal injury and motor behavioral impairments after traumatic brain injury","volume":"29","author":"Selvakumar","year":"2020","journal-title":"Exp. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1007\/s11064-020-02987-3","article-title":"An effective NADPH oxidase 2 inhibitor provides neuroprotection and improves functional outcomes in animal model of traumatic brain injury","volume":"45","author":"Wang","year":"2020","journal-title":"Neurochem. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1177\/0271678X17738701","article-title":"A combination antioxidant therapy to inhibit NOX2 and activate Nrf2 decreases secondary brain damage and improves functional recovery after traumatic brain injury","volume":"38","author":"Chandran","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1177\/0963689717714102","article-title":"Traumatic brain injury: Current treatment strategies and future endeavors","volume":"26","author":"Galgano","year":"2017","journal-title":"Cell Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.3389\/fnins.2019.01178","article-title":"Brain\u2013immune interactions and neuroinflammation after traumatic brain injury","volume":"13","author":"Dinet","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Crupi, R., Cordaro, M., Cuzzocrea, S., and Impellizzeri, D. (2020). Management of traumatic brain injury: From present to future. Antioxidants, 9.","DOI":"10.3390\/antiox9040297"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.wneu.2019.07.039","article-title":"A review of the molecular mechanisms of traumatic brain injury","volume":"131","author":"Ladak","year":"2019","journal-title":"World Neurosurg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4116","DOI":"10.3390\/ijerph120404116","article-title":"Functioning and disability analysis of patients with traumatic brain injury and spinal cord injury by using the world health organization disability assessment schedule 2.0","volume":"12","author":"Kuo","year":"2015","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12974-020-01863-9","article-title":"Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury","volume":"17","author":"Wang","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nrneurol.2017.13","article-title":"The far-reaching scope of neuroinflammation after traumatic brain injury","volume":"13","author":"Simon","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_22","first-page":"213","article-title":"Traumatic brain injury: An overview of epidemiology, pathophysiology, and medical management","volume":"104","author":"Capizzi","year":"2020","journal-title":"Med. Clin."},{"key":"ref_23","first-page":"443","article-title":"Pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and neuropsychiatric clinical expression","volume":"44","author":"Shively","year":"2021","journal-title":"Psychiatr. Clin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.expneurol.2015.08.018","article-title":"Microglia in the TBI brain: The good, the bad, and the dysregulated","volume":"275","author":"Loane","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3389\/fnagi.2017.00208","article-title":"Microglial activation in traumatic brain injury","volume":"9","author":"Donat","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/s12974-020-02005-x","article-title":"Cellular infiltration in traumatic brain injury","volume":"17","author":"Alam","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12974-022-02430-0","article-title":"Hydroxychloroquine attenuates neuroinflammation following traumatic brain injury by regulating the TLR4\/NF-\u03baB signaling pathway","volume":"19","author":"Hu","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.nbd.2018.05.016","article-title":"Selective NLRP3 inflammasome inhibitor reduces neuroinflammation and improves long-term neurological outcomes in a murine model of traumatic brain injury","volume":"117","author":"Xu","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.brainres.2015.04.035","article-title":"VEGI attenuates the inflammatory injury and disruption of blood\u2013brain barrier partly by suppressing the TLR4\/NF-\u03baB signaling pathway in experimental traumatic brain injury","volume":"1622","author":"Gao","year":"2015","journal-title":"Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1007\/s12035-014-8752-3","article-title":"Interactions of oxidative stress and neurovascular inflammation in the pathogenesis of traumatic brain injury","volume":"51","author":"Chandra","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"582","DOI":"10.3389\/fneur.2019.00582","article-title":"Endothelial targeted strategies to combat oxidative stress: Improving outcomes in traumatic brain injury","volume":"10","author":"Lutton","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.neuro.2022.02.002","article-title":"Biological determinants impact the neurovascular toxicity of nicotine and tobacco smoke: A pharmacokinetic and pharmacodynamic perspective","volume":"89","author":"Archie","year":"2022","journal-title":"NeuroToxicology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15573","DOI":"10.1038\/s41598-019-51728-2","article-title":"Cigarette smoke extract exacerbates hyperpermeability of cerebral endothelial cells after oxygen glucose deprivation and reoxygenation","volume":"9","author":"Bernard","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.2174\/0929867321666131217153310","article-title":"Oxidative stress in traumatic brain injury","volume":"21","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.expneurol.2015.05.024","article-title":"Treatment of traumatic brain injury with anti-inflammatory drugs","volume":"275","author":"Bergold","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.brainres.2015.12.024","article-title":"Therapies negating neuroinflammation after brain trauma","volume":"1640","author":"Hellewell","year":"2016","journal-title":"Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.freeradbiomed.2018.12.014","article-title":"Melatonin receptor activation provides cerebral protection after traumatic brain injury by mitigating oxidative stress and inflammation via the Nrf2 signaling pathway","volume":"131","author":"Wang","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.2147\/DDDT.S163951","article-title":"Baicalin provides neuroprotection in traumatic brain injury mice model through Akt\/Nrf2 pathway","volume":"12","author":"Fang","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12974-017-0895-5","article-title":"Isoliquiritigenin alleviates early brain injury after experimental intracerebral hemorrhage via suppressing ROS-and\/or NF-\u03baB-mediated NLRP3 inflammasome activation by promoting Nrf2 antioxidant pathway","volume":"14","author":"Zeng","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sajja, R.K., Green, K.N., and Cucullo, L. (2015). Altered nrf2 signaling mediates hypoglycemia-induced blood\u2013brain barrier endothelial dysfunction in vitro. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122358"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5636","DOI":"10.1158\/1078-0432.CCR-16-0775","article-title":"Molecular pathways: Dietary regulation of stemness and tumor initiation by the ppar-\u03b4 pathway","volume":"22","author":"Beyaz","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_43","first-page":"2614","article-title":"Metformin\u2013a future therapy for neurodegenerative diseases","volume":"34","author":"Sikora","year":"2017","journal-title":"Pharm. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5852706","DOI":"10.1155\/2018\/5852706","article-title":"The role of Nrf2 signaling in PPAR\u03b2\/\u03b4-mediated vascular protection against hyperglycemia-induced oxidative stress","volume":"2018","author":"Jimenez","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s11011-014-9632-2","article-title":"Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia","volume":"30","author":"Ashabi","year":"2015","journal-title":"Metab. Brain Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"119343","DOI":"10.1016\/j.lfs.2021.119343","article-title":"Repurposing metformin to treat age-related neurodegenerative disorders and ischemic stroke","volume":"274","author":"Sharma","year":"2021","journal-title":"Life Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.brainresbull.2018.04.008","article-title":"Neuroprotective effects of metformin on traumatic brain injury in rats associated with NF-\u03baB and MAPK signaling pathway","volume":"140","author":"Tao","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Sivandzade, F., and Cucullo, L. (2019). Anti-Diabetic Countermeasures Against Tobacco Smoke-Dependent Cerebrovascular Toxicity: Use and Effect of Rosiglitazone. Int. J. Mol. Sci., 20.","DOI":"10.1186\/s12868-019-0497-5"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.redox.2017.02.007","article-title":"Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity","volume":"12","author":"Prasad","year":"2017","journal-title":"Redox Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sivandzade, F., and Cucullo, L. (2019). Assessing the protective effect of rosiglitazone against electronic cigarette\/tobacco smoke-induced blood\u2013brain barrier impairment. BMC Neurosci., 20.","DOI":"10.1186\/s12868-019-0497-5"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12987-015-0014-x","article-title":"Impact of cigarette smoke extract and hyperglycemic conditions on blood\u2013brain barrier endothelial cells","volume":"12","author":"Prasad","year":"2015","journal-title":"Fluids Barriers CNS"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e20180037","DOI":"10.1542\/peds.2018-0037","article-title":"The Biomarker S100B and Mild Traumatic Brain Injury: A Meta-analysis","volume":"141","author":"Oris","year":"2018","journal-title":"Pediatrics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1089\/neu.2012.2579","article-title":"S100b as a prognostic biomarker in outcome prediction for patients with severe traumatic brain injury","volume":"30","author":"Goyal","year":"2013","journal-title":"J. Neurotrauma"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3259295","DOI":"10.1155\/2019\/3259295","article-title":"MMP-9 Contributes to Dendritic Spine Remodeling Following Traumatic Brain Injury","volume":"2019","author":"Pijet","year":"2019","journal-title":"Neural Plast"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"9294","DOI":"10.1007\/s12035-018-1061-5","article-title":"Elevation of MMP-9 Levels Promotes Epileptogenesis After Traumatic Brain Injury","volume":"55","author":"Pijet","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1089\/neu.2014.3764","article-title":"Matrix Metalloproteinase Expression in Contusional Traumatic Brain Injury: A Paired Microdialysis Study","volume":"32","author":"Guilfoyle","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7122","DOI":"10.1111\/jcmm.16741","article-title":"Impact of chronic smoking on traumatic brain microvascular injury: An in vitro study","volume":"25","author":"Sivandzade","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s12974-020-01818-0","article-title":"The cerebrovascular and neurological impact of chronic smoking on post-traumatic brain injury outcome and recovery: An in vivo study","volume":"17","author":"Sivandzade","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7963","DOI":"10.1073\/pnas.1812413116","article-title":"Ubiquitin C-terminal hydrolase L1 (UCH-L1) loss causes neurodegeneration by altering protein turnover in the first postnatal weeks","volume":"116","author":"Reinicke","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1042\/CS20160043","article-title":"COPD and stroke: Are systemic inflammation and oxidative stress the missing links?","volume":"130","author":"Austin","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Naik, P., Fofaria, N., Prasad, S., Sajja, R.K., Weksler, B., Couraud, P.O., Romero, I.A., and Cucullo, L. (2014). Oxidative and pro-inflammatory impact of regular and denicotinized cigarettes on blood brain barrier endothelial cells: Is smoking reduced or nicotine-free products really safe?. BMC Neurosci., 15.","DOI":"10.1186\/1471-2202-15-51"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1080\/15287394.2015.1043607","article-title":"Oxidative stress induced by cigarette smoke extracts in human brain cells (T98G) and human brain microvascular endothelial cells (HBMEC) in mono-and co-culture","volume":"78","author":"Kim","year":"2015","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_63","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_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1759091419899782","article-title":"NRF2 as a therapeutic target in neurodegenerative diseases","volume":"12","author":"Brandes","year":"2020","journal-title":"ASN Neuro"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.diabet.2015.02.003","article-title":"Antidiabetic agents: Potential anti-inflammatory activity beyond glucose control","volume":"41","author":"Scheen","year":"2015","journal-title":"Diabetes Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"113475","DOI":"10.1016\/j.bbr.2021.113475","article-title":"Metformin reduces oxandrolone-induced depression-like behavior in rats via modulating the expression of IL-1\u03b2, IL-6, IL-10 and TNF-\u03b1","volume":"414","author":"Hammad","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1161\/CIRCRESAHA.116.308445","article-title":"Anti-inflammatory effects of metformin irrespective of diabetes status","volume":"119","author":"Cameron","year":"2016","journal-title":"Circ. Res."},{"key":"ref_68","first-page":"54","article-title":"Metformin and its anti-inflammatory and anti-oxidative effects; new concepts","volume":"8","author":"Abbaszadeh","year":"2019","journal-title":"J. Ren. Inj. Prev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"637","DOI":"10.14336\/AD.2018.0513","article-title":"The anti-inflammatory and anti-oxidant mechanisms of the Keap1\/Nrf2\/ARE signaling pathway in chronic diseases","volume":"10","author":"Tu","year":"2019","journal-title":"Aging Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1177\/1933719117697128","article-title":"Rosiglitazone regulates TLR4 and rescues HO-1 and NRF2 expression in myometrial and decidual macrophages in inflammation-induced preterm birth","volume":"24","author":"Kadam","year":"2017","journal-title":"Reprod. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/biolre\/ioy186","article-title":"Rosiglitazone augments antioxidant response in the human trophoblast and prevents apoptosis","volume":"100","author":"Kilburn","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"630","DOI":"10.4103\/1673-5374.180749","article-title":"A mouse model of weight-drop closed head injury: Emphasis on cognitive and neurological deficiency","volume":"11","author":"Khalin","year":"2016","journal-title":"Neural Regen Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.2147\/DDDT.S174037","article-title":"Notch inhibitor can attenuate apparent diffusion coefficient and improve neurological function through downregulating NOX2-ROS in severe traumatic brain injury","volume":"12","author":"Zhang","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Jarrahi, A., Braun, M., Ahluwalia, M., Gupta, R., Wilson, M., Munie, S., Ahluwalia, P., Vender, J.R., Vale, F.L., and Dhandapani, K.M. (2020). Revisiting traumatic brain injury: From molecular mechanisms to therapeutic interventions. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100389"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"370312","DOI":"10.1155\/2015\/370312","article-title":"Traumatic brain injury and NADPH oxidase: A deep relationship","volume":"2015","author":"Angeloni","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.nbd.2018.06.003","article-title":"Bexarotene protects against neurotoxicity partially through a PPARgamma-dependent mechanism in mice following traumatic brain injury","volume":"117","author":"He","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1111\/cns.13265","article-title":"Rosiglitazone polarizes microglia and protects against pilocarpine-induced status epilepticus","volume":"25","author":"Peng","year":"2019","journal-title":"CNS Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.neulet.2017.02.075","article-title":"PPAR-gamma agonist rosiglitazone reduces autophagy and promotes functional recovery in experimental traumaticspinal cord injury","volume":"650","author":"Li","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.2174\/1389557521666210304112403","article-title":"Glitazones, PPAR-gamma and Neuroprotection","volume":"21","author":"Kumar","year":"2021","journal-title":"Mini. Rev. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nrd.2015.21","article-title":"From blood\u2013brain barrier to blood\u2013brain interface: New opportunities for CNS drug delivery","volume":"15","author":"Banks","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.tins.2015.08.003","article-title":"The molecular constituents of the blood\u2013brain barrier","volume":"38","author":"Chow","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3389\/fnins.2020.00513","article-title":"Effects of drugs of abuse on the blood-brain barrier: A brief overview","volume":"14","author":"Pimentel","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_83","unstructured":"Laskowitz, D., and Grant, G. (2016). Blood\u2013Brain Barrier Pathophysiology Following Traumatic Brain Injury, CRC Press\/Taylor and Francis Group. Chapter 4. PMID: 26583184."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.1002\/cncr.11409","article-title":"Serum S100beta: A noninvasive marker of blood-brain barrier function and brain lesions","volume":"97","author":"Kanner","year":"2003","journal-title":"Cancer"},{"key":"ref_85","first-page":"109","article-title":"Peripheral markers of brain damage and blood-brain barrier dysfunction","volume":"21","author":"Marchi","year":"2003","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fncel.2016.00002","article-title":"A review of the mechanisms of blood-brain barrier permeability by tissue-type plasminogen activator treatment for cerebral ischemia","volume":"10","author":"Suzuki","year":"2016","journal-title":"Front. Cell. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1177\/1535370216650940","article-title":"Induction of matrix metalloproteinase-1 by tumor necrosis factor-\u03b1 is mediated by interleukin-6 in cultured fibroblasts of keratoconus","volume":"241","author":"Du","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"101059","DOI":"10.1016\/j.redox.2018.11.017","article-title":"NRF2 and NF-\u049bB interplay in cerebrovascular and neurodegenerative disorders: Molecular mechanisms and possible therapeutic approaches","volume":"21","author":"Sivandzade","year":"2019","journal-title":"Redox Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s12974-016-0738-9","article-title":"Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation","volume":"13","author":"Corrigan","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-kappaB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s12974-017-0917-3","article-title":"Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1\/TLR4\/NF-\u03baB pathway following experimental traumatic brain injury","volume":"14","author":"Chen","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12974-017-0819-4","article-title":"Microglial-derived microparticles mediate neuroinflammation after traumatic brain injury","volume":"14","author":"Kumar","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e622","DOI":"10.1002\/ams2.622","article-title":"Thorough overview of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein as tandem biomarkers recently cleared by US Food and Drug Administration for the evaluation of intracranial injuries among patients with traumatic brain injury","volume":"8","author":"Wang","year":"2021","journal-title":"Acute Med. Surg."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"113524","DOI":"10.1016\/j.expneurol.2020.113524","article-title":"Abolishing UCHL1\u2032s hydrolase activity exacerbates TBI-induced axonal injury and neuronal death in mice","volume":"336","author":"Mi","year":"2021","journal-title":"Exp. Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"13256","DOI":"10.1074\/jbc.M314124200","article-title":"Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson\u2019s and Alzheimer\u2019s diseases","volume":"279","author":"Choi","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Namani, A., Matiur Rahaman, M., Chen, M., and Tang, X. (2018). Gene-expression signature regulated by the KEAP1-NRF2-CUL3 axis is associated with a poor prognosis in head and neck squamous cell cancer. BMC Cancer, 18.","DOI":"10.1186\/s12885-017-3907-z"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"583","DOI":"10.3233\/JAD-151146","article-title":"AVN-101: A multi-target drug candidate for the treatment of CNS disorders","volume":"53","author":"Ivachtchenko","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"25659","DOI":"10.1038\/srep25659","article-title":"Pharmacokinetics and tolerability of NSC23925b, a novel P-glycoprotein inhibitor: Preclinical study in mice and rats","volume":"6","author":"Gao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neulet.2018.05.045","article-title":"Conventional and electronic cigarettes dysregulate the expression of iron transporters and detoxifying enzymes at the brain vascular endothelium: In vivo evidence of a gender-specific cellular response to chronic cigarette smoke exposure","volume":"682","author":"Kaisar","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_100","first-page":"125","article-title":"Diabetes Mellitus and Blood-Brain Barrier Dysfunction: An Overview","volume":"2","author":"Prasad","year":"2014","journal-title":"J. Pharm."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"12708","DOI":"10.1038\/s41598-018-31137-7","article-title":"In Vitro Modulation of Redox and Metabolism Interplay at the Brain Vascular Endothelium: Genomic and Proteomic Profiles of Sulforaphane Activity","volume":"8","author":"Sajja","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.neulet.2017.05.059","article-title":"Blood-brain barrier disruption in diabetic mice is linked to Nrf2 signaling deficits: Role of ABCB10?","volume":"653","author":"Sajja","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"13340","DOI":"10.1038\/s41598-018-31623-y","article-title":"GM1 ganglioside prevents axonal regeneration inhibition and cognitive deficits in a mouse model of traumatic brain injury","volume":"8","author":"Benady","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s12640-020-00288-9","article-title":"Acute traumatic brain injury-induced neuroinflammatory response and neurovascular disorders in the brain","volume":"39","author":"Kempuraj","year":"2021","journal-title":"Neurotox. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1124\/jpet.116.235333","article-title":"Inhibition of AAK1 kinase as a novel therapeutic approach to treat neuropathic pain","volume":"358","author":"Kostich","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.neulet.2015.05.015","article-title":"Altered glycaemia differentially modulates efflux transporter expression and activity in hCMEC\/D3 cell line","volume":"598","author":"Sajja","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Sivandzade, F., Bhalerao, A., and Cucullo, L. (2019). Cerebrovascular and neurological disorders: Protective role of NRF2. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143433"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6219\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:03:07Z","timestamp":1760122987000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,25]]},"references-count":107,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076219"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076219","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,25]]}}}