{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T07:01:04Z","timestamp":1783234864420,"version":"3.54.6"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordination of Personnel Improvement of Higher Level","award":["0001"],"award-info":[{"award-number":["0001"]}]},{"name":"Coordination of Personnel Improvement of Higher Level","award":["APP 0107\/2016"],"award-info":[{"award-number":["APP 0107\/2016"]}]},{"name":"Coordination of Personnel Improvement of Higher Level","award":["312388\/2021-7"],"award-info":[{"award-number":["312388\/2021-7"]}]},{"name":"Coordination of Personnel Improvement of Higher Level","award":["407833\/2023-4"],"award-info":[{"award-number":["407833\/2023-4"]}]},{"name":"Research Support Foundation of the State of Bahia","award":["0001"],"award-info":[{"award-number":["0001"]}]},{"name":"Research Support Foundation of the State of Bahia","award":["APP 0107\/2016"],"award-info":[{"award-number":["APP 0107\/2016"]}]},{"name":"Research Support Foundation of the State of Bahia","award":["312388\/2021-7"],"award-info":[{"award-number":["312388\/2021-7"]}]},{"name":"Research Support Foundation of the State of Bahia","award":["407833\/2023-4"],"award-info":[{"award-number":["407833\/2023-4"]}]},{"name":"National Council for Scientific and Technological Development","award":["0001"],"award-info":[{"award-number":["0001"]}]},{"name":"National Council for Scientific and Technological Development","award":["APP 0107\/2016"],"award-info":[{"award-number":["APP 0107\/2016"]}]},{"name":"National Council for Scientific and Technological Development","award":["312388\/2021-7"],"award-info":[{"award-number":["312388\/2021-7"]}]},{"name":"National Council for Scientific and Technological Development","award":["407833\/2023-4"],"award-info":[{"award-number":["407833\/2023-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) has a complex and multifactorial pathology and is a major cause of death and disability for humans. Immediately after TBI, astrocytes and microglia react with complex morphological and functional changes known as reactive gliosis to form a glial scar in the area immediately adjacent to the lesion, which is the major barrier to neuronal regeneration. The flavonoid agathisflavone (bis-apigenin), present in Poincianella pyramidalis leaves, has been shown to have neuroprotective, neurogenic, and anti-inflammatory effects, demonstrated in vitro models of glutamate-induced toxicity, neuroinflammation, and demyelination. In this study, we evaluated the effect and mechanisms of agathisflavone in neuronal integrity and in the modulation of gliosis in an ex vivo model of TBI. For this, microdissections from the encephalon of Wistar rats (P6-8) were prepared and subjected to mechanical injury (MI) and treated or not with daily agathisflavone (5 \u03bcM) for 3 days. Astrocyte reactivity was investigated by measuring mRNA and expression of GFAP protein in the lesioned area by immunofluorescence and Western blot. The proportion of microglia was determined by immunofluorescence for Iba-1; mRNA expression for inflammasome NRPL3 and interleukin-1 beta (IL-1\u03b2) was determined by RT-qPCR. It was observed that lesions in the cortical tissue induced astrocytes overexpressing GFAP in the typical glial scar formed and that agathisflavone modulated GFAP expression at the transcriptional and post-transcriptional levels, which was associated with a reduction of the glial scar. MI induced an increase in the proportion of microglia (Iba-1+), which was not observed in agathisflavone-treated cultures. Moreover, the flavonoid modulated negatively both the NRLP3 and IL-1\u03b2 mRNA expression that was increased in the lesioned area of the tissue. These findings support the regulatory properties of agathisflavone in the control of the inflammatory response in glial cells, which can impact neuroprotection and should be considered for future studies for TB and other pathological conditions of the central nervous system.<\/jats:p>","DOI":"10.3390\/ijms26031275","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T04:36:51Z","timestamp":1738557411000},"page":"1275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Flavonoid Agathisflavone Attenuates Glia Activation After Mechanical Injury of Cortical Tissue and Negatively Regulates Both NRLP3 and IL-1\u03b2 Expression"],"prefix":"10.3390","volume":"26","author":[{"given":"Ver\u00f4nica Moreira","family":"de Sousa","sequence":"first","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1urea Maria Alves Nunes","family":"Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Short","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6430-229X","authenticated-orcid":false,"given":"Balbino Lino","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, BA, Brazil"},{"name":"College of Nursing, Federal University of Vale do S\u00e3o Francisco, Petrolina 56304-917, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8032-9663","authenticated-orcid":false,"given":"Victor Diogenes Amara","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-9055","authenticated-orcid":false,"given":"Jorge Mauricio","family":"David","sequence":"additional","affiliation":[{"name":"Department of General and Inorganic Chemistry, Institute of Chemistry, Federal University of Bahia, Salvador 40170-110, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleonice Creusa dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8975-3871","authenticated-orcid":false,"given":"Silvia Lima","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.20344\/amp.4892","article-title":"Traumatic brain injury in Portugal: Trends in hospital admissions from 2000 to 2010","volume":"27","author":"Dias","year":"2014","journal-title":"Acta Medica Port."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1016\/j.bbadis.2017.05.020","article-title":"White matter damage after traumatic brain injury: A role for damage associated molecular patterns. Biochimica et biophysica acta","volume":"1863","author":"Braun","year":"2017","journal-title":"Mol. 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Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1275\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:25:28Z","timestamp":1760027128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,1]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26031275"],"URL":"https:\/\/doi.org\/10.3390\/ijms26031275","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,1]]}}}