{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T08:52:11Z","timestamp":1778403131309,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900402"],"award-info":[{"award-number":["81900402"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2020JQ-232"],"award-info":[{"award-number":["2020JQ-232"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Mild traumatic brain injury (mTBI) without skull fracturing is the most common occurrence of all TBIs and is considered as a serious public health concern. Animal models of mTBI are essential to investigation of TBI and its effects. In the current study, we developed and characterized a reproducible mouse model of mild TBI, meanwhile, the effects of this mTBI model, as well as repetitive mTBIs (rmTBIs), on the endothelial function of mouse aortas were also studied. In variety of closed-head models of mTBI, impact velocity, weight, and dwell time are the main parameters that affect the severities of injury. Here, we used a device, converting parameters of velocity, tip weight, and dwell time into impact force, to develop a mouse model of close-head mTBI. Mice were subjected to a mild TBI induced by the impact forces of 500, 600, 700 and 800 kdyn, respectively. Later, brain injuries were assessed histologically and molecularly. Systemic and brain inflammation were measured by plasma cytokine assay and glial fibrillary acidic protein (GFAP) staining. The composite neurobehavioral test revealed significant acute functional deficits in mice after mTBI, corresponding to the degree of injury. Mice brain undergoing mTBI had significant elevated GFAP staining. Plasma cytokines interleukin-1\u03b2 (IL-1\u03b2) and superoxide dismutase (SOD) were significantly increased within 2 h after mTBI. Taken together, these data suggest that the mTBI mouse model introduce within our study exhibits good repeatability and comparable pathological characters. Moreover, we used this mTBI mouse model to determine the effect of single or rmTBIs on systemic vasoconstriction and relaxation. The isometric-tension results indicate that rmTBIs induce a pronounced and long-lasting endothelial dysfunction in mouse aorta.<\/jats:p>","DOI":"10.3390\/brainsci12020232","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T01:03:40Z","timestamp":1644368620000},"page":"232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["mTBI-Induced Systemic Vascular Dysfunction in a Mouse mTBI Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8820-5120","authenticated-orcid":false,"given":"Weizhen","family":"Lv","sequence":"first","affiliation":[{"name":"Institute of Medical Research, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medical Research, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanxue","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Xi\u2019an Jiaotong University Health Science Center, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Medical Research, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0694-813X","authenticated-orcid":false,"given":"Jiaxi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Xi\u2019an Jiaotong University Health Science Center, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingjuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Medical Research, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/B978-0-444-52892-6.00004-0","article-title":"The neuropathology of traumatic brain injury","volume":"127","author":"McKee","year":"2015","journal-title":"Handb. Clin. Neurol."},{"key":"ref_2","unstructured":"Kobeissy, F.H. (2015). Animal Models for Concussion: Molecular and Cognitive Assessments-Relevance to Sport and Military Concussions. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects, Frontiers in Neuroengineering."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1212\/WNL.0000000000004214","article-title":"The spectrum of mild traumatic brain injury: A review","volume":"89","author":"Mayer","year":"2017","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/aet2.10053","article-title":"Emergency Physician Training on Mild Traumatic Brain Injury: A Systematic Review","volume":"1","author":"Patrick","year":"2017","journal-title":"AEM Educ. Train."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1089\/neu.2012.2349","article-title":"Challenges in the development of rodent models of mild traumatic brain injury","volume":"30","author":"Dewitt","year":"2013","journal-title":"J. Neurotrauma"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/B978-0-444-63954-7.00003-3","article-title":"Mild traumatic brain injury and concussion: Terminology and classification","volume":"158","author":"Sussman","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s40478-020-00924-7","article-title":"Biological links between traumatic brain injury and Parkinson\u2019s disease","volume":"8","author":"Delic","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1771","DOI":"10.1212\/WNL.0000000000005522","article-title":"Mild TBI and risk of Parkinson disease: A Chronic Effects of Neurotrauma Consortium Study","volume":"90","author":"Gardner","year":"2018","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12974-019-1407-6","article-title":"The TRPC6 inhibitor, larixyl acetate, is effective in protecting against traumatic brain injury-induced systemic endothelial dysfunction","volume":"16","author":"Chen","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1089\/neu.2015.4340","article-title":"Traumatic Brain Injury Causes Endothelial Dysfunction in the Systemic Microcirculation through Arginase-1-Dependent Uncoupling of Endothelial Nitric Oxide Synthase","volume":"34","author":"Villalba","year":"2017","journal-title":"J. Neurotrauma"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/S1474-4422(15)00002-2","article-title":"Diagnosis, prognosis, and clinical management of mild traumatic brain injury","volume":"14","author":"Levin","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.wneu.2016.03.045","article-title":"Epidemiology of Global Pediatric Traumatic Brain Injury: Qualitative Review","volume":"91","author":"Dewan","year":"2016","journal-title":"World Neurosurg."},{"key":"ref_13","unstructured":"Permenter, C.M., Fernandez-de Thomas, R.J., and Sherman, A. (2021). Postconcussive Syndrome, StatPearls Publishing."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1089\/neu.2018.6127","article-title":"A Systematic Review of Closed Head Injury Models of Mild Traumatic Brain Injury in Mice and Rats","volume":"36","author":"Bodnar","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.jss.2013.03.075","article-title":"A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits","volume":"184","author":"Yang","year":"2013","journal-title":"J. Surg. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.neubiorev.2004.06.002","article-title":"Motor and cognitive function evaluation following experimental traumatic brain injury","volume":"28","author":"Fujimoto","year":"2004","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"348","DOI":"10.3389\/fneur.2020.00348","article-title":"Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury","volume":"11","author":"Edwards","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/SHK.0000000000000037","article-title":"Interleukin 6 mediates neuroinflammation and motor coordination deficits after mild traumatic brain injury and brief hypoxia in mice","volume":"40","author":"Yang","year":"2013","journal-title":"Shock"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/19336934.2015.1085623","article-title":"The gut reaction to traumatic brain injury","volume":"9","author":"Katzenberger","year":"2015","journal-title":"Fly (Austin)"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/B978-0-444-52892-6.00014-3","article-title":"Systemic manifestations of traumatic brain injury","volume":"127","author":"Gaddam","year":"2015","journal-title":"Handb. Clin. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1177\/0271678X19897443","article-title":"Repetitive mTBI is associated with age-related reductions in cerebral blood flow but not cortical thickness","volume":"41","author":"Clark","year":"2021","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000358765","article-title":"Cumulative effects of repetitive mild traumatic brain injury","volume":"28","author":"Bailes","year":"2014","journal-title":"Prog. Neurol. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1089\/neu.2006.0011","article-title":"Electromagnetic controlled cortical impact device for precise, graded experimental traumatic brain injury","volume":"24","author":"Brody","year":"2007","journal-title":"J. Neurotrauma"},{"key":"ref_25","first-page":"921","article-title":"Molecular mechanisms and signaling pathways of reactive astrocytes responding to traumatic brain injury","volume":"36","author":"Li","year":"2021","journal-title":"Histol. Histopathol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Michinaga, S., and Koyama, Y. (2021). Pathophysiological Responses and Roles of Astrocytes in Traumatic Brain Injury. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126418"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s40478-021-01297-1","article-title":"Temporal patterns of microglial activation in white matter following experimental mild traumatic brain injury: A systematic literature review","volume":"9","author":"Velayudhan","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ponomarenko, A., Tyrtyshnaia, A., Ivashkevich, D., and Manzhulo, I. (2021). Mild Traumatic Brain Injury Contributes to the Development of Delayed Neuroinflammation. Neuroimmunomodulation, 1\u20138.","DOI":"10.1159\/000519011"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"McAteer, K.M., Corrigan, F., Thornton, E., Turner, R.J., and Vink, R. (2016). Short and Long Term Behavioral and Pathological Changes in a Novel Rodent Model of Repetitive Mild Traumatic Brain Injury. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160220"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s12974-020-01854-w","article-title":"Neuroinflammatory mechanisms of post-traumatic epilepsy","volume":"17","author":"Mukherjee","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI59643","article-title":"Macrophage plasticity and polarization: In vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"174","DOI":"10.2174\/187152710791012053","article-title":"Assessing activation states in microglia","volume":"9","author":"Colton","year":"2010","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tweedie, D., Fukui, K., Li, Y., Yu, Q.S., Barak, S., Tamargo, I.A., Rubovitch, V., Holloway, H.W., Lehrmann, E., and Wood, W.H. (2016). Cognitive Impairments Induced by Concussive Mild Traumatic Brain Injury in Mouse Are Ameliorated by Treatment with Phenserine via Multiple Non-Cholinergic and Cholinergic Mechanisms. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156493"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"zqab018","DOI":"10.1093\/function\/zqab018","article-title":"Traumatic Brain Injury Impairs Systemic Vascular Function through Disruption of Inward-Rectifier Potassium Channels","volume":"2","author":"Sackheim","year":"2021","journal-title":"Function (Oxf.)"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/2\/232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:16:04Z","timestamp":1760134564000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/2\/232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,8]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["brainsci12020232"],"URL":"https:\/\/doi.org\/10.3390\/brainsci12020232","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,8]]}}}