TY  - JOUR
PY  - 2017//
TI  - White matter damage after traumatic brain injury: a role for damage associated molecular patterns
JO  - Biochimica et biophysica acta
A1  - Braun, Molly
A1  - Vaibhav, Kumar
A1  - Saad, Nancy M.
A1  - Fatima, Sumbul
A1  - Vender, John R.
A1  - Baban, Babak
A1  - Hoda, Md Nasrul
A1  - Dhandapani, Krishnan M.
SP  - 2614
EP  - 2626
VL  - 1863
IS  - 10 Pt B
N2  - 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. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis edited by Dr. Raghavan Raju.<br><br>Copyright © 2017. Published by Elsevier B.V.<p />  <p>Language: en</p>
LA  - en
SN  - 0006-3002
UR  - http://dx.doi.org/10.1016/j.bbadis.2017.05.020
ID  - ref1
ER  -