Astrocyte activation persists one year after TBI: a dynamic shift from inflammation to neurodegeneration

作者：Hadi Abou‐El‐Hassan, Taha Yahya, Benjamin E. Zusman, Omar Albastaki, Harm T Imkamp, Jessica Ye, Francesca Percopo, Jonathan R Christenson, Maryam H. Al Mansi, K. Lu, Galina Gabriely, Bruna K. Tatematsu, Karl J. Habashy, Juliana Romano Lopes, Amir‐Hadi Maghzi, Rafael M. Rezende, Francisco J. Quintana, Howard L. Weiner, Saef Izzy · 发表于：Communications Biology · 年份：2025 · DOI：10.1038/s42003-025-09138-w · 被引用次数：5 · 研究领域：Traumatic Brain Injury and Neurovascular Disturbances、Neuroinflammation and Neurodegeneration Mechanisms、Neurogenesis and neuroplasticity mechanisms

Traumatic brain injury (TBI) remains a leading cause of chronic neurological impairment, yet the cellular mechanisms underlying long-term neurodegeneration in TBI remain incompletely understood. Astrocytes, the most abundant glial cell type, are central to maintaining neuroglial and neurovascular homeostasis. Following TBI, however, astrocytic activation contributes to sustained inflammation and neurotoxicity. In this study, we employed immunohistochemistry and RNA sequencing to longitudinally profile astrocyte morphology and transcriptional states at acute (2 days), subacute (2 weeks), and chronic (1 year) stages after controlled cortical impact in mice. We identified a temporally evolving astrocyte response-beginning with a pro-inflammatory profile acutely, transitioning through a profile suggestive of mixed inflammatory and neurodegenerative signatures subacutely, and culminating in a chronic state marked generally by expression of Alzheimer's and Parkinson's disease-associated genes. Notably, a subset of astrocyte-derived progenitor cells also was found up to one-year post-injury, expressing markers associated with neurogenesis. These findings reveal that astrocyte activation is not transient but persists chronically, undergoing a dynamic shift from inflammation to degeneration. The observed parallels between astrocyte states in chronic TBI and neurodegenerative disorders underscore their potential role in post-traumatic cognitive decline and highlight astrocyte-targeted ...