White matter damage after traumatic brain injury: A role for damage associated molecular patterns

Molly Braun, Kumar Vaibhav, Nancy M. Saad, Sumbul Fatima, John R. Vender, Babak Baban, Md Nasrul Hoda, Krishnan M. Dhandapani

Research output: Contribution to journalReview articlepeer-review

63 Scopus citations


Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. Despite decades of pre-clinical investigation, therapeutic strategies focused on acute neuroprotection failed to improve TBI outcomes. This lack of translational success has necessitated a reassessment of the optimal targets for intervention, including a heightened focus on secondary injury mechanisms. Chronic immune activation correlates with progressive neurodegeneration for decades after TBI; however, significant challenges remain in functionally and mechanistically defining immune activation after TBI. In this review, we explore the burgeoning evidence implicating the acute release of damage associated molecular patterns (DAMPs), such as adenosine 5′-triphosphate (ATP), high mobility group box protein 1 (HMGB1), S100 proteins, and hyaluronic acid in the initiation of progressive neurological injury, including white matter loss after TBI. The role that pattern recognition receptors, including toll-like receptor and purinergic receptors, play in progressive neurological injury after TBI is detailed. Finally, we provide support for the notion that resident and infiltrating macrophages are critical cellular targets linking acute DAMP release with adaptive immune responses and chronic injury after TBI. The therapeutic potential of targeting DAMPs and barriers to clinical translational, in the context of TBI patient management, are discussed.

Original languageEnglish (US)
Pages (from-to)2614-2626
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number10
StatePublished - Oct 2017


  • HMGB1
  • Leukocyte
  • Lymphocyte
  • Macrophage
  • Microglia
  • Oligodendrocyte
  • S100
  • T-cell
  • Toll like receptor
  • White matter injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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