Table 1.
TBI Biomarkers
| TBI biomarker | Function | References |
|---|---|---|
| GFAP | Serum glial fibrillary acidic protein breakdown products in mild and moderate TBI are associated with intracranial lesions and neurosurgical intervention. | 141, 142 |
| S100β | S100β is a 21 kDa calcium-binding protein (Ca2+), found mainly in the cytosol of astroglial cells and Schwann cells. S100B may be a reliable marker of brain damage in TBI without multiple trauma at 24 h. | 143–145 |
| Myelin-basic protein (MBP) | TBI-induced axonal injury could cause damage to the myelin structure, resulting in secondary myelin sheath instability and demyelination, which may increase the vulnerability of the axons. | 146 |
| NSE | Enolase is a glycolytic enzyme and NSE is one of its five isoenzymes. NSE levels are particularly elevated in severe TBI. | 36, 142 |
| NFH (neurofilament heavy chain) | NFH is an axonal injury marker. Serum NFH levels are significantly elevated in diffuse axonal injury (DAI). | 37, 147 |
| Tau | Microtubule-associated structural protein in axons. Shearing of axons leads to the disruption of Tau binding to tubulin, and subsequent Tau hyperphosphorylation can lead to the formation of Tau oligomers. These can cause self-propagating Tau pathology under specific conditions. | 148 |
| Tumor necrosis factor-alpha (TNF-α) | Pro-inflammatory cytokine that plays an essential role in the immune response observed in patients post-TBI. When TNFα levels are unregulated and chronically elevated, they can drive neurodegenerative cascades. | 149 |
| Interleukin-6 | Pro-inflammatory cytokine that has been implicated in TBI patients and, when elevated levels are not regulated, then can drive neurodegenerative processes. | 150 |
| Ubiquitin C-terminal hydrolase-L1 (UCH-L1) | The addition or removal of ubiquitin from proteins that are destined for metabolism; this is a key part in the removal of excessive, oxidized or misfolded proteins during both normal and pathological conditions in neurons. It is abundant in neurons and has been thought of as a possible biomarker for TBI. It has previously been associated with severe TBI, an increased mortality rate at 6 weeks, and a poor 6-month GOS score. | 151–153 |
| Alpha II-spectrin (SBDPs) | Principally found in neurons and is in plentiful supply in axons and pre-synaptic terminals. The protein is processed into breakdown products (SBDPs) - specifically, SBDP150 (150 kDa size) and SBDP145 (145 kDa) by calpain, and into SBDP120 (120 kDa) by caspase-3. SBDPs are found across cellular and animal models of TBI, and levels are elevated in the CSF of humans particularly after severe TBI. SBDP150, −145, and −120 show a different temporal pattern after TBI, particularly in differentiating survivors from non-survivors. | 50, 154 |
| Estradiol and testosterone | Female TBI patients, in general, recover better than male TBI patients – postulating that differential levels of progesterone and other sex hormones may act as neuroprotective agents. However, increased oestradiol and testosterane levels over time have been associated with increased mortality and worse global outcome for both men and women. | 155, 156 |
CSF, cerebrospinal fluid; GFAP, glial fibrillary acidic protein; GOS, Glasgow Outcome Scale; NSE, neuron-specific enolase; TBI, traumatic brain injury.