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. Author manuscript; available in PMC: 2020 Mar 1.
Published in final edited form as: Neurobiol Dis. 2018 Jul 17;123:59–68. doi: 10.1016/j.nbd.2018.07.017

Table 1.

List of major pathobiological events and affected structures, injury mechanism(s), and candidate protein biomarkers of epileptogenicity after TBI.

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
a

Pathological changes that occur predominantly or exclusively after penetrating TBI. Bold faced markers have shown prognostic value in PTE.