Military traumatic brain injury: a challenge straddling neurology and psychiatry

Table 3 Emerging biomarkers of TBI

Mechanism	Biomarkers	Sample source	Detection technology	Utility^*	References
Damage of neuron cell body	UCH-L1	Serum	Sandwich ELISA	1	[114]
	NSE	CSF	Electro chemiluminescent assay		[115]
Damage of astrocytes	GFAP	Serum	Sandwich ELISA	1, 2, 3, 4	[116]
	S100-B	Serum; CSF	Automatic electrochemiluminescence immunoassay	1, 2, 4	[117, 118]
Death of neuron	SBDPs	CSF	Bicinchoninic acid microprotein assays	1	[119]
Damage of axon	NF proteins	CSF	ELISA and size-exclusion chromatography and mass spectrometry	1, 2, 4	[120]
Damage of white matter	MBP	Serum; CSF	ELISA	1, 2	[121]
Post-injury neurodegeneration and autoimmune response	Total Tau and phospho-Tau	Brain tissue	Immunohistochemical analysis	1, 2, 4	[122]
	Brain antigen-targeting autoantibodies	Serum	ELISA	3, 4	[123]
Chronic neuronal dendrite regeneration	MAP-2	Serum	ELISA	4	[124]
Survival and regeneration of neurons and axons	BNDF	Serum	Electro chemiluminescent sandwich immunoassay	4	[125]
	NRGN				[126]
	VEGF, etc.		Automatic clotting instrument, etc		[124]
Damage of brain	miRNA	Serum	TaqMan microRNA assays and RT-PCR	1, 5	[127]
	HIF-1α		Immunofluorescence staining		[118]
	Caspase 3 and C5b-9				[118]
Damage of neuron^**	CNA	Serum	PCR	1, 2	[128]
	Exosome and microvesicles	Serum; CSF	Precipitation reagent and nano sight imaging technology		[129]

In the above studies, the subjects were not limited to military personnel, so the possibility of negative results in the population of military TBI patients cannot be ruled out
UCH-L1 Ubiquitin carboxy-terminal hydrolase L1, NSE Neuron specific enolase, GFAP Glial fibrillary acidic protein S100-B Central nervous system specific protein-B, SBDPs αII-spectrin breakdown products, NF Proteins Neurofilament proteins, MBP Myelin basic protein, MAP-2 Microtubule-associated protein-2, BNDF Brain derived nerve growth factor, NRGN Postsynaptic protein neurogranin, CNA Circulating nucleic acids, PCR Polymerase chain reaction, RT-PCR Reverse transcription-polymerase chain reaction, VEGF Vascular endothelial growth factor, HIF-1α Hypoxia-inducible factor-1 alpha, C5b-9 Terminal complement complex, CSF Cerebrospinal fluid, ELISA Enzyme-linked immunosorbent assay, Ref References
^*The utility here refers only to potential utility, and its accuracy is questionable because most biomarker studies are only experimental and have not been applied in clinical settings. Diagnosis = 1; Prediction = 2; Clinical Classification = 3; Chronic Monitoring = 4; Death Review = 5
^**Total free DNA levels in patients' plasma are an independent predictor of traumatic death in cases of severe traumatic brain injury

ISSN: 2054-9369