Traumatic brain injury (TBI) continues to be a major healthcare problem and there is much to be explored regarding the secondary pathobiology to identify early predictive markers and new therapeutic targets. While documented changes in thrombosis and inflammation in major trauma have been well described, growing evidence suggests that isolated TBI also results in systemic alterations in these mechanisms. Here, we review recent experimental and clinical findings that demonstrate how blood-brain barrier dysfunction, systemic immune response, inflammation, platelet activation, and thrombosis contribute significantly to the pathogenesis of TBI. Despite advances in the links between thrombosis and inflammation, there is a lack of treatment options aimed at both processes and this could be crucial to treating vascular injury, local and systemic inflammation, and secondary ischemic events following TBI. With emerging evidence of newly-identified roles for platelets, leukocytes, the coagulation system and extracellular vesicles in processes of inflammation and thrombosis, there is a growing need to characterize these mechanisms within the context of TBI and whether these changes persist into the chronic phase of injury. Importantly, this review defines areas in need of further research to advance the field and presents a roadmap to identify new diagnostic and treatment options for TBI.
|Number of pages
|Published - Feb 2021
Bibliographical noteFunding Information:
The meeting that inspired this review was supported by a field-based meeting award from the Department of Veterans Affairs Biomedical Laboratory Research & Development (BLR&D) Service. This work was supported by BLR&D Career Development Award Number [grant number IK2 BX004618 ] from the Department of Veterans Affairs awarded to WBH. RER was supported by BLR&D Merit Review Award [grant number I01 BX002551 ] from the Department of Veterans Affairs , JFD was supported by the NIH [grant numbers R21NS087296 ; R01HL152200 ]. The content is solely the responsibility of the authors and does not represent the official views of National Institutes of Health, Department of Veterans Affairs or the United States government.
- Blast injury
- Blood-brain barrier dysfunction
- Extracellular vesicles
- Mild TBI
- von Willebrand factor
ASJC Scopus subject areas