Table 1.
Event and affected structure(s) | Injury mechanism(s) | Candidate protein biomarkers |
---|---|---|
Skull fracturea | Primary (mechanotransductive mechanisms) | Alkaline phosphatase, BMPs, OPN |
Dura penetration or damagea | Primary | Leptomeningeal proteins (β-trace), glycosaminoglycans, inflammatory molecules |
Hemorrhage, hematomaa | Primary | Hemoglobin (CSF), fibrinogen (CSF) |
Metabolic changes, reactive oxygen species | Primary (hypoxia, altered energy demands, ion homeostasis and neurotransmission, toxic substances) | HIF1α, HNE, SOD2, Ceruloplasmin, HSP70 |
Axonal injury and/or loss | Primary and secondary (e.g., inflammation) | NF-L, NF-H, tau, p-tau |
Disruption of cell adhesion and extracellular matrix | Primary and secondary (e.g., inflammation) | MMP9, Integrin-α6, 1TMP1, TIMP4, Connexin-43, NCAD, ICAM1, NCAM1 |
Neuronal and glial damage or death | Primary and secondary (metabolic dysregulation and neuroinflammation) | Neuronal: UCHL1, NSE, CK-BB Glial: GFAP, ALDOC, BLBP, PEA15, GS, S100β, MBP |
Vascular changes, edema | Primary and secondary (neuroinflammation, BBB disruption, metabolic stress, toxic substances) | VEGF, VEGF-R1 (Flk1), pVEGF-R1, Claudin-5, vWF, AQP4, Occludin, VCAM1, CSF/serum albumin ratio |
Cellular proliferation, astrogliosis | Secondary | GFAP, BDNF, glial cell-derived neurotrophic factor (GDNF) |
Synaptic remodeling | Secondary | BDNF, GDNF |
Neuroinflammation | Secondary | Chemo/cytokines, Interleukins (IL1β in CSF), TLR signaling molecules, OPN, fibrinogen, and DAMPs (HSP70, IIMGB1, S100β) |
Autoimmune response | Secondary | MBP (in CSF), Immunoglobulin G (CSF), autoantibodies |
Pathological changes that occur predominantly or exclusively after penetrating TBI. Bold faced markers have shown prognostic value in PTE.