{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:35:13Z","timestamp":1790274913270,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Imperial College Alzheimer Research UK network","award":["ARUK-2014NC-IMP"],"award-info":[{"award-number":["ARUK-2014NC-IMP"]}]},{"name":"the Wellcome Trust Networks of Excellence","award":["ARUK-2014NC-IMP"],"award-info":[{"award-number":["ARUK-2014NC-IMP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>There is compelling evidence that head injury is a significant environmental risk factor for Alzheimer\u2019s disease (AD) and that a history of traumatic brain injury (TBI) accelerates the onset of AD. Amyloid-\u03b2 plaques and tau aggregates have been observed in the post-mortem brains of TBI patients; however, the mechanisms leading to AD neuropathology in TBI are still unknown. In this study, we hypothesized that focal TBI induces changes in miRNA expression in and around affected areas, resulting in the altered expression of genes involved in neurodegeneration and AD pathology. For this purpose, we performed a miRNA array in extracts from rats subjected to experimental TBI, using the controlled cortical impact (CCI) model. In and around the contusion, we observed alterations of miRNAs associated with dementia\/AD, compared to the contralateral side. Specifically, the expression of miR-9 was significantly upregulated, while miR-29b, miR-34a, miR-106b, miR-181a and miR-107 were downregulated. Via qPCR, we confirmed these results in an additional group of injured rats when compared to na\u00efve animals. Interestingly, the changes in those miRNAs were concomitant with alterations in the gene expression of mRNAs involved in amyloid generation and tau pathology, such as \u03b2-APP cleaving enzyme (BACE1) and Glycogen synthase-3-\u03b2 (GSK3\u03b2). In addition increased levels of neuroinflammatory markers (TNF-\u03b1), glial activation, neuronal loss, and tau phosphorylation were observed in pericontusional areas. Therefore, our results suggest that the secondary injury cascade in TBI affects miRNAs regulating the expression of genes involved in AD dementia.<\/jats:p>","DOI":"10.3390\/biom12101457","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T22:18:13Z","timestamp":1665526693000},"page":"1457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Traumatic Brain Injury Leads to Alterations in Contusional Cortical miRNAs Involved in Dementia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0994-1881","authenticated-orcid":false,"given":"Shahmir","family":"Naseer","sequence":"first","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Abelleira-Hervas","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhwani","family":"Savani","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"de Burgh","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robertas","family":"Aleksynas","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius K.","family":"Donat","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1104-5805","authenticated-orcid":false,"given":"Nelofer","family":"Syed","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Sastre","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/oxfordjournals.aje.a009724","article-title":"Traumatic brain injury and time to onset of Alzheimer\u2019s disease: A population-based study","volume":"149","author":"Nemetz","year":"1999","journal-title":"Am. 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