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<p>Traumatic brain injury (TBI) remains a leading cause of chronic neurological impairment, yet the cellular mechanisms underlying long-term&#xa0;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 interventions as a promising avenue for therapeutic development.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月4日

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  • Hadi Abou-El-Hassan,
  • Taha Yahya,
  • Benjamin E. Zusman,
  • Omar Albastaki,
  • Harm T. Imkamp,
  • Jessica J. Ye,
  • Francesca Percopo,
  • Jonathan R. Christenson,
  • Maryam H. Al Mansi,
  • Kuan-Jung Lu,
  • Galina Gabriely,
  • Bruna K. Tatematsu,
  • Karl J. Habashy,
  • Juliana R. Lopes,
  • Amir-Hadi Maghzi,
  • Rafael M. Rezende,
  • Francisco J. Quintana,
  • Howard L. Weiner,
  • Saef Izzy

摘要

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 interventions as a promising avenue for therapeutic development.