{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:14:41Z","timestamp":1786374881996,"version":"build-2736575974"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Traumatic brain injury (TBI) is a major cause of death and long-term disability in the United States. The initial primary injury in TBI is followed by a secondary injury cascade of molecular events, which can persist for years, and contributes to neuroinflammation, neurodegeneration, and long-term functional deficits after TBI. In this review, we will discuss evidence that cellular senescence in TBI, where damaged cells enter a state of permanent cell-cycle arrest and release pro-inflammatory factors, is a component of the secondary injury cascade, which contributes to both chronic neuroinflammation and long-term neurodegeneration after TBI. There is now abundant evidence that a single moderate to severe TBI or repeated mild TBI leads to DNA damage and oxidative stress, which triggers cellular senescence in the injured brain. The induction of cellular senescence leads to production of a cocktail of pro-inflammatory cytokines, chemokines, and matrix remodeling proteases, collectively termed the senescence associated secretory phenotype (SASP). While the SASP may be beneficial acutely in certain situations, chronically it has been suggested to promote a pro-inflammatory and pro-neurodegenerative environment. Additional work using both global and cell-specific knockout animal models indicates that the cGAS-STING signaling pathway helps connect cellular damage to the SASP, as it detects cytosolic DNA in damaged cells and regulates SASP production. Finally, we will discuss future directions for the field, and review evidence that therapeutically targeting of senescent cells through administration of senolytic drugs in animal models leads to attenuated neuroinflammation and neurodegeneration in the injured brain, and enhances functional outcome after TBI.<\/jats:p>","DOI":"10.3389\/fnins.2026.1862748","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:45:35Z","timestamp":1785905135000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellular senescence and senolytic therapy in traumatic brain injury"],"prefix":"10.3389","volume":"20","author":[{"given":"Darrell W.","family":"Brann","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harminder D","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan M.","family":"Dhandapani","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/s12974-018-1354-7","article-title":"STING-mediated type-I interferons contribute to the neuroinflammatory process and detrimental effects following traumatic brain injury","volume":"15","author":"Abdullah","year":"2018","journal-title":"J. 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