{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:22:25Z","timestamp":1760235745390,"version":"build-2065373602"},"reference-count":104,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Traumatic brain injury (TBI) represents one of the leading causes of mortality and morbidity worldwide, placing an enormous socioeconomic burden on healthcare services and communities around the world. Survivors of TBI can experience complications ranging from temporary neurological and psychosocial problems to long-term, severe disability and neurodegenerative disease. The current lack of therapeutic agents able to mitigate the effects of secondary brain injury highlights the urgent need for novel target discovery. This study comprises two independent systematic reviews, investigating both microRNA (miRNA) and proteomic expression in rat models of severe TBI (sTBI). The results were combined to perform integrated miRNA-protein co-expression analyses with the aim of uncovering the potential roles of miRNAs in sTBI and to ultimately identify new targets for therapy. Thirty-four studies were included in total. Bioinformatic analysis was performed to identify any miRNA\u2013protein associations. Endocytosis and TNF signalling pathways were highlighted as common pathways involving both miRNAs and proteins found to be differentially expressed in rat brain tissue following sTBI, suggesting efforts to find novel therapeutic targets that should be focused here. Further high-quality investigations are required to ascertain the involvement of these pathways and their miRNAs in the pathogenesis of TBI and other CNS diseases and to therefore uncover those targets with the greatest therapeutic potential.<\/jats:p>","DOI":"10.3390\/cells10092425","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T23:34:11Z","timestamp":1631662451000},"page":"2425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Co-Expression Network Analysis of MicroRNAs and Proteins in Severe Traumatic Brain Injury: A Systematic Review"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8192-1052","authenticated-orcid":false,"given":"Claire","family":"Osgood","sequence":"first","affiliation":[{"name":"Neuroscience and Ophthalmology Group, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-6442","authenticated-orcid":false,"given":"Zubair","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Neuroscience and Ophthalmology Group, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Centre for Trauma Sciences Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Surgical Reconstruction and Microbiology Research Centre, National Institute for Health Research, Queen Elizabeth Hospital, Birmingham B15 2TH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9430-4723","authenticated-orcid":false,"given":"Valentina","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Neuroscience and Ophthalmology Group, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Centre for Trauma Sciences Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Surgical Reconstruction and Microbiology Research Centre, National Institute for Health Research, Queen Elizabeth Hospital, Birmingham B15 2TH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28148","DOI":"10.1038\/srep28148","article-title":"A Panel of Serum MiRNA Biomarkers for the Diagnosis of Severe to Mild Traumatic Brain Injury in Humans","volume":"6","author":"Bhomia","year":"2016","journal-title":"Sci. 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