{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T08:30:26Z","timestamp":1782981026415,"version":"3.54.5"},"reference-count":31,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Israel Innovation Authority: Kamin Incentive Program","award":["2024874"],"award-info":[{"award-number":["2024874"]}]},{"name":"Israel Innovation Authority: Kamin Incentive Program","award":["IDE\/2024\/000719"],"award-info":[{"award-number":["IDE\/2024\/000719"]}]},{"name":"University of Oviedo from the Agencia Sekuens (Gobierno del Principado de Asturias)","award":["2024874"],"award-info":[{"award-number":["2024874"]}]},{"name":"University of Oviedo from the Agencia Sekuens (Gobierno del Principado de Asturias)","award":["IDE\/2024\/000719"],"award-info":[{"award-number":["IDE\/2024\/000719"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this study, we assessed the ability of 2-Cl-MGV-1 (2-chlorophenyl quinazolin-4-yl, dimethyl carbamate), a ligand of the 18 kDa mitochondrial translocator protein (TSPO), to mitigate brain damage in a mouse model of traumatic brain injury (TBI). TSPO is important for arresting the death of neurons and glia and counteracting microglial activation, and it provides anti-inflammatory activity, promotes regeneration (including neurons), and contributes to angiogenesis. We assessed the minimal dose of the TSPO ligand 2-Cl-MGV-1 that attenuates the magnitude of brain damage as well as the time window following TBI in which the treatment is effective. We found that 7.5 mg\/kg of 2-Cl-MGV-1 can reduce the impact of the TBI as assessed by magnetic resonance imaging (MRI). We also found that 2-Cl-MGV-1 improved motor performance as observed in a treadmill test (80.9% fewer shocks needed and 40.7% more distance covered, both p &lt; 0.05), and reduced anatomical brain damage (by 86.5%, p &lt; 0.05), cell death (by 75.0%, p &lt; 0.001), and microglial inflammatory response (by 50.2%, p &lt; 0.01). The treatment also increased expression of neuronal markers NeuN and \u03b23-tubulin (30.0%, p &lt; 0.01; 36.0%, p &lt; 0.01, respectively). The time window in which we found the treatment to be effective was 3\u201311 h after TBI. Our study suggests that agents active at the TSPO can significantly attenuate the outcome of TBI, including in the structural, cellular, and neuro-behavioral dimensions. The mechanisms involved in the attenuation of brain damage following TBI may be related to a decrease in cell death and to anti-inflammatory activity. TSPO seems to be a novel target for the development of agents aimed at the suppression of neurodegenerative processes.<\/jats:p>","DOI":"10.3390\/ijms26104854","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T07:34:03Z","timestamp":1747640043000},"page":"4854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TSPO Ligand 2-Cl-MGV-1 Mitigates Traumatic Brain Injury (TBI) in a Mouse Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1742-2787","authenticated-orcid":false,"given":"Nasra","family":"Yasin","sequence":"first","affiliation":[{"name":"The Ruth and Bruce Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, Haifa 31096, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Veenman","sequence":"additional","affiliation":[{"name":"The Ruth and Bruce Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, Haifa 31096, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0242-9620","authenticated-orcid":false,"given":"Beatriz","family":"Caballero","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain"},{"name":"Instituto de Neurociencias del Principado de Asturias (INEUROPA), 33003 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4393-8739","authenticated-orcid":false,"given":"Nidal","family":"Zeineh","sequence":"additional","affiliation":[{"name":"The Ruth and Bruce Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, Haifa 31096, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2257-9012","authenticated-orcid":false,"given":"Laura","family":"Gonzalez-Blanco","sequence":"additional","affiliation":[{"name":"Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain"},{"name":"Servicio Regional de Investigaci\u00f3n y Desarrollo Agroalimentario (SERIDA), 33300 Villaviciosa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9765-8938","authenticated-orcid":false,"given":"Abraham","family":"Weizman","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Laboratory of Molecular and Biological Psychiatry, Felsenstein Medical Research Center, Petah Tikva 4910002, Israel"},{"name":"Research Unit, Geha Mental Health Center, Petah Tikva 4910002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Gavish","sequence":"additional","affiliation":[{"name":"The Ruth and Bruce Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, Haifa 31096, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"Cpg1","DOI":"10.2519\/jospt.2020.0301","article-title":"Physical Therapy Evaluation and Treatment After Concussion\/Mild Traumatic Brain Injury","volume":"50","author":"Shimamura","year":"2020","journal-title":"J. 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