Cellular Senescence in Traumatic Brain Injury: Evidence and Perspectives

• Published in: Frontiers in aging neuroscience Vol. 13; p. 742632
• Main Authors: Schwab, Nicole, Leung, Emily, Hazrati, Lili-Naz
• Format: Journal Article
• Language: English
• Published: Lausanne Frontiers Research Foundation 28.09.2021; Frontiers Media S.A
• Subjects: Aging; Alzheimer's disease; Animal models; brain trauma; Cell cycle; cellular senescence; chronic traumatic encephalopathy; Coma; Concussion; Consciousness; Cyclin-dependent kinases; Dementia; Dementia disorders; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Enzymes; Excitotoxicity; Gene expression; Gliosis; Inflammation; Kinases; mild traumatic brain injury; Neurodegenerative diseases; Neurological complications; Neuroscience; Patients; Proteins; Senescence; Therapeutic applications; Traumatic brain injury
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2021.742632

Mild traumatic brain injury (mTBI) can lead to long-term neurological dysfunction and increase one's risk of neurodegenerative disease. Several repercussions of mTBI have been identified and well-studied, including neuroinflammation, gliosis, microgliosis, excitotoxicity, and proteinopathy – however the pathophysiological mechanisms activating these pathways after mTBI remains controversial and unclear. Emerging research suggests DNA damage-induced cellular senescence as a possible driver of mTBI-related sequalae. Cellular senescence is a state of chronic cell-cycle arrest and inflammation associated with physiological aging, mood disorders, dementia, and various neurodegenerative pathologies. This narrative review evaluates the existing studies which identify DNA damage or cellular senescence after TBI (including mild, moderate, and severe TBI) in both experimental animal models and human studies, and outlines how cellular senescence may functionally explain both the molecular and clinical manifestations of TBI. Studies on this subject clearly show accumulation of various forms of DNA damage (including oxidative damage, single-strand breaks, and double-strand breaks) and senescent cells after TBI, and indicate that cellular senescence may be an early event after TBI. Further studies are required to understand the role of sex, cell-type specific mechanisms, and temporal patterns, as senescence may be a pathway of interest to target for therapeutic purposes including prognosis and treatment.