Metabolomics in severe traumatic brain injury: a scoping review

Fedoruk, Riley Page; Lee, Chel Hee; Banoei, Mohammad Mehdi; Winston, Brent W.

doi:10.1186/s12868-023-00824-1

BMC Neuroscience

Table 2 Human metabolome database (HMDB) classification of collected metabolites by class (bolded)

From: Metabolomics in severe traumatic brain injury: a scoping review

HMDB class	Metabolite	Sample type	Change identified	Supplemental	Refs.
Fatty acyls
	Isobutyrylcarnitine	Serum/Plasma	Decrease	Significant decrease in sTBI patients compared to healthy volunteers, orthopedic patients and mTBI	Jeter et al. [27]
	Isoleucine	Serum/Plasma	Decrease	Significant decrease in sTBI patients compared to healthy volunteers, orthopedic patients and mTBI	Jeter et al. [27]
	Propionylcarnitine	Serum/Plasma	Decrease	Decent reduction in sTBI patients compared to healthy volunteers	Jeter et al. [27]
	Succinylcarnitine	Serum/Plasma	Decrease	Only differed by a decrease in sTBI patients compared to orthopedic injury patients	Jeter et al. [27]
	Hydroxyisovaleryl carnitine	Serum/Plasma	Decrease	Found decreased exclusively in sTBI patients compared to healthy volunteers	Jeter et al. [27]
	Octanoic acid	Serum/Microdialysate	Increase	Found upregulated in sTBI patients and remained high in most patients	Oresic et al. [33]
	Decanoic acid	Serum/Microdialysate	Increase	Found upregulated in sTBI patients and remained high in most patients	Oresic et al. [33]
	Octanoic acid	Serum/Plasma	Increase	As TBI severity increased, octanoic acid increased	Thomas et al. [32]
	Decanoic acid	Serum/Plasma	Increase	As TBI severity increased, decanoic acid increased	Thomas et al. [32]
	2-methylbutyrylcarnitine	Serum/Plasma	Decrease	Significant decrease in sTBI patients compared to healthy volunteers and mTBI	Jeter et al. [27]
	Isovalerylcarnitine	Serum/Plasma	Decrease	Significant decrease in sTBI patients compared to healthy volunteers, orthopedic controls, and mTBI	Jeter et al. [27]
Keto acids and derivatives
	α-ketobutyrate	Serum/Plasma	Increase	Found significantly increased in the plasma of sTBI patients	Dash et al. [29]
	Methylglutarylcarnitine	Serum/Plasma	Increase	Plasma levels were found significantly increased in sTBI patients compared to healthy volunteers, orthopedic controls, and mTBI	Jeter et al. [27]
	4-methyl-2-oxopentanoate	Serum/Plasma	Decrease	Decreased in sTBI patients compared to healthy volunteers	Jeter et al. [27]
	3-methyl-2-oxovalerate	Serum/Plasma	Decrease	Significant decrease in sTBI patients compared to healthy volunteers, orthopedic patients, and mTBI	Jeter et al. [27]
Carboxylic acids and derivatives
	Methionine	Serum/Plasma	Decrease	Significant reduction in plasma relative to healthy volunteers	Dash et al. [29]
	Betaine	Serum/Plasma	Decrease	Significantly reduced compared to mTBI group and healthy volunteers	Dash et al. [29]
	Dimethylglycine	Serum/Plasma	Decrease	Significant decrease in sTBI patients relative to healthy volunteers	Dash et al. [29]
	Cysteine	Serum/Plasma	Decrease	Showed a significant reduction in sTBI patients	Dash et al. [29]
	Glycine	Serum/Plasma	Decrease	Significantly reduced in sTBI and mTBI	Dash et al. [29]
	Gamma-glutamylvaline	Serum/Plasma	Decrease	Relative levels were found significantly decreased in sTBI patients	Dash et al. [29]
	Gamma-glutamylleucine	Serum/Plasma	Decrease	Relative levels were found significantly decreased in sTBI patients	Dash et al. [29]
	Gamma-glutamylisoleucine	Serum/Plasma	Decrease	Relative levels were found significantly decreased in sTBI patients	Dash et al. [29]
	Gamma-glutamyltyrosine	Serum/Plasma	Decrease	Relative levels were found significantly decreased in sTBI patients	Dash et al. [29]
	Gamma-glutamylphenylalanine	Serum/Plasma	Decrease	Relative levels were found significantly decreased in sTBI patients	Dash et al. [29]
	5-oxoproline	Serum/Plasma	Decrease	Significantly reduced in sTBI patients compared to mTBI and healthy volunteers	Dash et al. [29]
	2-Aminobutyric acid	Serum/Plasma/Microdialysate	Decrease	Found lower concentrations in patients with detectable CT features following TBI	Dickens et al. [36]
	Citrulline	Serum/Plasma	Decrease	Significantly reduced in the plasma of sTBI patients	Jeter et al. [26]
	Ornithine	Serum/Plasma	Decrease	Significant decrease in the plasma of sTBI patients compared to healthy volunteers, orthopedic controls, and mTBI patients	Jeter et al. [26]
	Proline	Serum/Plasma	Decrease	Significantly reduced in the plasma of sTBI patients compared to healthy volunteers, orthopedic controls, and mTBI patients	Jeter et al. [26]
	4-Hydroxyproline	Serum/Plasma	Decrease	Significantly reduced in the plasma of sTBI patients compared to healthy volunteers, orthopedic controls, and mTBI patients	Jeter et al. [26]
	Creatine	Serum/Plasma	Increase	Significantly increased in sTBI patients compared to HC and orthopedic controls	Jeter et al. [26]
	Valine	Serum/Plasma	Decrease	Significantly decreased during the first week post sTBI compared to controls	Vuille-Dit-Bille [35]
	Valine	Serum/Plasma	Decrease	Reduction in valine levels detected in the plasma of sTBI patients compared to all other groups	Jeter et al. [27]
	Serine	Serum/Microdialysate	Decrease	Found downregulated in all TBIs, more strongly in sTBI	Oresic et al. [33]
	Leucine	Serum/Plasma	Decrease	Significantly decreased during the first week post sTBI compared to controls	Vuille-Dit-Bille [35]
	Isoleucine	Serum/Plasma	Decrease	Significantly decreased during the first week post sTBI compared to controls	Vuille-Dit-Bille [35]
	Leucine	Serum/Plasma	Decrease	Decrease in patients with sTBI compared to healthy volunteers and mTBI patients	Jeter et al. [27]
	Alanine	Serum/Microdialysate	Decrease	Found downregulated in all TBIs, more strongly in sTBI	Oresic et al. [33]
	Glutamine	CSF	Increase	Statistically increasing trend in moTBI and sTBI patients compared to non-injured controls	Glenn et al. [37]
	Creatinine	CSF	Decrease	Significantly decreased concentrations of total creatinine in moTBI and sTBI patients	Glenn et al. [37]
	Proline	Serum/Plasma	Decrease	≤ 60% the conc. in arterial plasma and jugular blood compared to HC	Wolahan et al. [34]
	Hydroxyproline	Serum/Plasma	Decrease	≤ 60% the conc. in jugular blood compared to HC	Wolahan et al. [34]
	Serine	Serum/Plasma	Decrease	≤ 60% the conc. in jugular blood compared to HC	Wolahan et al. [34]
	Citrulline	Serum/Plasma	Decrease	≤ 60% the conc. in jugular blood compared to HC	Wolahan et al. [34]
	eNAA	Microdialysate	Decrease	Steep decline of extracellular NAA seen in 8 patients early on	Shannon et al. [28]
	Phenylalanine	Serum/Plasma	Increase	Significantly increased during the first posttraumatic week following TBI	Vuille-Dit-Bille [35]
	Methionine	Urine	Increase	Significant negative correlation (increase) to patients decreasing GCS scores	Bykowski et al. [30]
	NAA	MR Imaging	Decrease	Decrease in patients with differing degrees of TBI, including sTBI	Marino et al. [25]
	L-arginine	Serum/Plasma	Decrease	Significant reduction compared to healthy volunteers, orthopedic injury patients, and mTBI	Jeter et al. [26]
	Serine	Serum/Plasma	Decrease	Found decreased in TBI patients overall	Thomas et al. [32]
	Alanine	Serum/Plasma	Decrease	Found decreased in TBI patients overall	Thomas et al. [32]
	Glutamate	CSF	Increase	Significantly increased compared to control and survival groups	Stefani et al. [38]
	Tyrosine	Serum/Plasma	Increase	Significantly increased for both posttraumatic weeks following TBI	Vuille-Dit-Bille [35]
	Asparagine	Serum/Plasma	Decrease	TBI blood had less than or equal to 60% the concentration of HC in jugular blood	Wolahan et al. [34]
	Threonine	Serum/Plasma	Decrease	Found decreased in TBI patients overall	Thomas et al. [32]
Hydroxy acids and derivatives
	2-hydroxybutyrate	Serum/Plasma	Increase	Found significantly increased in sTBI	Dash et al. [29]
	2-hydroxybutyric acid	Serum/Microdialysate	Increase	Found upregulated in sTBI patients	Oresic et al. [33]
	3-hydroxybutyric acid	Serum/Microdialysate	Increase	Found upregulated in sTBI patients	Oresic et al. [33]
	Lactate	CSF	Increase	A slight increase compared to non-injured controls in moTBI and sTBI patients	Glenn et al. [37]
	Lactate	CSF	Increase	Significantly increased compared to control and survival groups	Stefani et al. [38]
	Lactate	MR Images	Increase	Diffusely high signal of lactate resonance intensity in patients with acute TBI	Marino et al. [25]
Organooxygen compounds
	Inositol	Serum/Plasma/Microdialysate	Increase	Found to increase in patients with detectable pathology on a CT scan or the presence of a mass lesion	Dickens et al. [36]
	(2,3-BPG)	Serum/Microdialia	Increase	Found upregulated in sTBI patients and a strong association with TBI severity, roughly a 100-fold upregulation compared to controls	Oresic et al. [33]
	Propylene glycol	CSF	Increase	Significantly higher concentrations in moTBI and sTBI patients	Glenn et al. [37]
	Gluconate	Serum/Plasma	Decrease	TBI blood had less than or equal to 60% the concentration of HC in arterial plasma	Wolahan et al. [34]
	Glucose-6-phosphate	Serum/Plasma	Decrease	Significant decrease in jugular venous blood from arterial levels	Wolahan et al. [34]
	Glycerol	Microdialysis	Increase	Significant positive conc. correlations between extracellular NAA and glycerol of 8 patients	Shannon et al. [28]
	Ribonic acid	Serum/Plasma	Increase	Found to increase in patients with detectable pathology on a CT scan or the presence of a mass lesion following TBI	Dickens et al. [36]
	Kynurenine	CSF	Increase	Displayed median levels similar to control days 0–3, but at days 4 and 5 showed significant elevation over controls post sTBI	Yan et al. [62]
	Myo-inositol	Serum/Plasma	Increase	Found elevated in TBI patients and proportional to differing severity	Thomas et al. [32]
Organic carbonic acids and derivatives
	Urea	Serum/Plasma	Decrease	Significant decrease in plasma of sTBI patients compared to healthy volunteers, orthopedic controls, and mTBI patients	Jeter et al. [26]
Quinolines and derivatives
	Kynurenic acid	CSF	Increase	Increased post sTBI compared to controls and reached a plateau after day 2 which lasted until day 5	Yan et al. [62]
Pyridines and derivatives
	Niacinamide	Serum/Plasma	Decrease	TBI blood had less than or equal to 60% the concentration of HC in jugular blood	Wolahan et al. [34]
	Quinolinic acid	CSF	Increase	Concentration significantly increased between days 1 and 5 compared to controls	Yan et al. [62]
Imidazopyrimidines
	Xanthine	Serum/Plasma	Increase	Significant net cerebral release or increase in jugular venous blood	Wolahan et al. [34]
	Xanthine	Urine	Increase	Increased levels following recovery	Bykowski et al. [30]
	Hypoxanthine	Urine	Increase	Found increased following recovery	Bykowski et al. [30]
Diazines
	Thymine	Urine	Increase	Significant negative correlation (increase) to patients decreasing GCS scores	Bykowski et al. [30]
Purine nucleosides
	Adenosine	Urine	Increase	Found to be significantly upregulated over recovery	Bykowski et al. [30]
	Inosine	Urine	Increase	Found upregulated in urine	Bykowski et al. [30]
	Deoxyinosine	Urine	Increase	Found upregulated after recovery	Bykowski et al. [30]
	Guanosine	Urine	Increase	Found upregulated in urine	Bykowski et al. [30]
Indoles and derivatives
	Indole-3-propionic acid	Serum/Microdialysis	Decrease	Found downregulated in all TBIs, more strongly in sTBI	Oresic et al. [33]
	Tryptophan	CSF	Increase	Increased in CSF compared to controls between days 0 to 5 in sTBI, however, median concentrations did not change much	Yan et al. [62]
	Tryptophan	Plasma/Serum	Decrease	Decreased post sTBI in serum from days 0 to 4	Yan et al. [62]
Organonitrogen compounds
	Choline	Serum/Plasma	Decrease	Significantly reduced compared to mTBI and healthy volunteers	Dash et al. [29]
	Choline	Serum/Plasma	Increase	Net cerebral release or increase in jugular venous blood	Wolahan et al. [34]
	Choline	MR Imaging	Increase	From patients with differing degrees of TBI including sTBI	Marino et al. [25]
	Spermidine	Serum/Plasma	Decrease	Significantly lower levels post moTBI and sTBI	Huang et al. [65]

CSF cerebrospinal fluid; CT computed tomography; GCS Glasgow Coma Scale; HC healthy controls; HMDB Human Metabolome Database; mTBI minor traumatic brain injury; moTBI moderate traumatic brain injury; NAA N-acetylaspartate; sTBI severe traumatic brain injury; TBI traumatic brain injury

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