{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:37:51Z","timestamp":1789774671000,"version":"4.0.1"},"reference-count":48,"publisher":"SAGE Publications","issue":"13-14","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["304541\/2020-6"],"award-info":[{"award-number":["304541\/2020-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2020\/02988-7"],"award-info":[{"award-number":["2020\/02988-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:p>\n                    Traumatic brain injury (TBI) is the leading cause of death and neurological disabilities in young adults, representing a significant psychological and economic burden for patients, families, and society. Morbidity and mortality in TBI involve pathophysiological events such as rupture of the blood\u2013brain barrier, neuronal death, and neuroinflammation triggered by the initial trauma and subsequent secondary injuries. A proper understanding of these pathophysiological events involved in TBI is essential to find new targets for the treatment of this disease. The purpose of this study was to analyze the signaling pathways involved in pericontusional brain tissue in severe human TBI. Twenty-two frozen pericontusional brain tissue samples from patients with severe TBI indicated for surgery were analyzed and compared against autopsy brain tissue samples from neurologically healthy donors. The transcriptome analysis by large-scale RNA sequencing (RNA-Seq) was performed in TBI and controls in the exploratory phase. The QuantSeq 3\u2032 mRNA-Seq RNASeq was performed to identify altered gene expression triggered by TBI. Signaling pathway enrichment analysis identified increased expression of gene sets involved in inflammation, angiogenesis, extracellular matrix remodeling, and wound healing pathways, while genes related to ion transport and synaptic transmission were downregulated in TBI relative to controls. Moreover, upregulation of signaling pathways involving TNF\u03b1, NFkB, IL6-JAK-STAT, cholesterol homeostasis, inflammatory response, TGF\u03b2, epithelial\u2013mesenchymal transition, coagulation, apoptosis, p53, and angiogenesis was detected with predominant downstream activation of six transcription factors:\n                    <jats:italic toggle=\"yes\">NFKB2<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">FOS<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">RELB<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">KLF4<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">ATF3<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">EGR2<\/jats:italic>\n                    . Specific brain cell compartment analysis based on gene expression profiles previously reported in single-cell transcriptomes confirmed the upregulation of genes related to microglia, immune cells, and endothelial cells, in contrast to the downregulation of genes related to neurons, astrocytes, and mature oligodendrocyte compartments. Notably, the expression of\n                    <jats:italic toggle=\"yes\">CCL2<\/jats:italic>\n                    was significant and uniquely correlated with\n                    <jats:italic toggle=\"yes\">SPHK1<\/jats:italic>\n                    expression, linking inflammatory response to angiogenesis. The transcriptome profile of TBI revealed several differentially expressed genes related to inflammatory response but also to concomitant activation of signaling pathways involved in tissue repair. More specifically, the CCL2-SPHK1 axis was validated at gene and protein expression levels in TBI. Further studies elucidating their role in angiogenesis and promotion of brain tissue repair, together with their potential applicability as therapeutic targets, are warranted.\n                  <\/jats:p>","DOI":"10.1177\/08977151251410198","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:02:01Z","timestamp":1773234121000},"page":"1089-1100","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic Profile of Pericontusional Tissue in Human Severe Traumatic Brain Injury"],"prefix":"10.1177","volume":"43","author":[{"given":"Adaliana Sorg Mousessian","family":"Onohara","sequence":"first","affiliation":[{"name":"Department of Neurology, Faculdade de Medicina, Laboratory of Molecular and Cellular Biology (LIM15), Universidade de Sao Paulo, Sao Paulo, SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sueli Mieko","family":"Oba-Shinjo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculdade de Medicina, Laboratory of Molecular and Cellular Biology (LIM15), Universidade de Sao Paulo, Sao Paulo, SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor Nagai","family":"Yamaki","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Neurology, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Marcondes","family":"Lerario","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelos G.","family":"Kolias","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6452-1436","authenticated-orcid":false,"given":"Paula Rodrigues","family":"Sola","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculdade de Medicina, Laboratory of Molecular and Cellular Biology (LIM15), Universidade de Sao Paulo, Sao Paulo, SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella Gon\u00e7alves","family":"Cavalcante","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculdade de Medicina, Laboratory of Molecular and Cellular Biology (LIM15), Universidade de Sao Paulo, Sao Paulo, SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabele Fattori","family":"Moretti","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculdade de Medicina, Laboratory of Molecular and Cellular Biology (LIM15), Universidade de Sao Paulo, Sao Paulo, SP, 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