{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:47:16Z","timestamp":1792180036388,"version":"4.4.0"},"reference-count":82,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["FZNE-2024-0004"],"award-info":[{"award-number":["FZNE-2024-0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) is one of the most common forms of neurotrauma, accompanied by significant disruptions in neuronal homeostasis and intercellular communication. A key protein involved in these processes is connexin 43 (Cx43), which facilitates the formation of gap junctions in the astrocytic network. In this study, using confocal and immunofluorescence microscopy, ultrastructural analysis, and molecular modeling, we investigated the dynamics of Cx43 expression and structural changes in neuroglia during various post-traumatic periods following TBI. It was shown that in the acute phase, 24 h post-injury, there is a reduction in Cx43 expression, accompanied by apoptotic neuronal degradation, disruption of nuclear NeuN localization, and destruction of cellular ultrastructure. By 7 days post-injury, a significant increase in Cx43 levels was observed, along with the formation of protein aggregates associated with pronounced reactive astrogliosis. Peripheral blood analysis revealed persistent neutrophilia, lymphopenia, and reduced monocyte levels, reflecting a systemic inflammatory response and immunosuppression, which was corroborated by a custom-trained neural network-based computer vision model. Linear regression and correlation analyses further identified a strong positive association between normalized monocyte levels and Cx43 expression, a moderate negative correlation with lymphocytes, and no significant correlation with neutrophils. Using a custom-built computer vision model, we confirmed these hematological trends and detected subtle changes, such as early increases in platelet counts, that were not captured by manual evaluation. The model demonstrated strong performance in classifying common blood cell types and proved to be a valuable tool for monitoring dynamic post-traumatic shifts in blood. Molecular dynamics modeling of Cx43 identified a pH-dependent mechanism of conformational reorganization under post-traumatic acidosis, mediated by the interaction between protonated His142 and Glu103. This mechanism mimics the structural consequences of the pathogenic E103K mutation and may play a critical role in the neurotoxic effects of Cx43 in TBI. These findings highlight the complexity of Cx43 regulation under traumatic conditions and its potential significance as a target for neuroprotective therapy.<\/jats:p>","DOI":"10.3390\/ijms26188855","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T15:10:46Z","timestamp":1757603446000},"page":"8855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Investigation of the Expression, Localization, and Acidosis-Associated Conformational Changes in Connexin 43 in Traumatic Brain Injury with the Development of a Neural Network Model for Assessing Systemic Inflammation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1654-3451","authenticated-orcid":false,"given":"Chizaram","family":"Nwosu","sequence":"first","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Faculty of Bioengineering and Veterinary Medicine, Don State Technical University, Rostov-on-Don 344000, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4703-1616","authenticated-orcid":false,"given":"Evgeniya","family":"Kirichenko","sequence":"additional","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Faculty of Bioengineering and Veterinary Medicine, Don State Technical University, Rostov-on-Don 344000, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4349-5897","authenticated-orcid":false,"given":"Stanislav","family":"Bachurin","sequence":"additional","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Faculty of Bioengineering and Veterinary Medicine, Don State Technical University, Rostov-on-Don 344000, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5243-026X","authenticated-orcid":false,"given":"Mikhail","family":"Petrushan","sequence":"additional","affiliation":[{"name":"Wizntech LLC, Rostov-on-Don 344002, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9834-3989","authenticated-orcid":false,"given":"Alexey","family":"Ermakov","sequence":"additional","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Faculty of Bioengineering and Veterinary Medicine, Don State Technical University, Rostov-on-Don 344000, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0685-5281","authenticated-orcid":false,"given":"Rozaliia","family":"Nabiullina","sequence":"additional","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Faculty of Bioengineering and Veterinary Medicine, Don State Technical University, Rostov-on-Don 344000, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7420-085X","authenticated-orcid":false,"given":"Marya","family":"Kaplya","sequence":"additional","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Faculty of Bioengineering and Veterinary Medicine, Don State Technical University, Rostov-on-Don 344000, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8873-3625","authenticated-orcid":false,"given":"Alexander","family":"Logvinov","sequence":"additional","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Faculty of Bioengineering and Veterinary Medicine, Don State Technical University, Rostov-on-Don 344000, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4036-5410","authenticated-orcid":false,"given":"Stanislav","family":"Rodkin","sequence":"additional","affiliation":[{"name":"Research Laboratory \u201cMedical Digital Images Based on the Basic Model\u201d, Department of Bioengineering, Faculty of Bioengineering and Veterinary Medicine, Don State Technical University, Rostov-on-Don 344000, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.mcna.2019.11.001","article-title":"Traumatic Brain Injury","volume":"104","author":"Capizzi","year":"2020","journal-title":"Med. 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