Tion in the TBI brain, while (7) presents the opposite, that arterial

Tion in the TBI brain, while (7) presents the opposite, that arterial lactate is connected to cerebral lactate and subsequently cerebral glucose, represented in our network as Lactate COEXISTS_ WITH Glucose. As suggested in (4) above, the ratio of glucose to lactate is influenced by glutamate. It has been suggested that this may be a result of astrocytes responding to increased extracellular glutamate by increasing glycolysis and, thereby, lactate production [75].Although there have been a limited number of attempts to include multiple biomarkers in panels for TBI [67,76,77], these have not included some of the types of substances returned in our results. To a large degree the absence of consideration for such substances may be explained by their lack of specificity or their ubiquitous nature. The level of specificity as an analyte for these neglected substances is significantly higher for an individual marker to stand on its own, and substances that are frequent if not ubiquitous in normal physiology are not obvious as candidates for TBI identification. Taken on their own, glucose and calcium levels are not useful as measures of brain injury. However, a panel of markers could better represent the complex network of molecular changes that occur during TBI and changeTable 4 Verification of substances in TBI physiology and TBI biomarker researchChanges in trauma? 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Brain-derived neurotrophic factor Fibroblast growth factor 2 Glial fibrillary acidic protein Neuron-specific enolase S100B Amyloid beta-protein precursor Interleukin-6 Malondialdehyde Superoxide dismutase Glucose Lactate Dopamine Norepinephrine Calcium Melatonin Glutamate Calpain+Changes in blood? Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes* Yes* No+Previously studied? Yes Yes Yes Yes Yes Yes No No No No No No No No No No No+PMIDs 11585248, 22528282, 20679891 11320217, 7696886 16266720, 22528282, 21079180 16716992, 22528282 19257803, 22528282, 21079180 8140894, 15258792 20850781, 20858121 11280646, 11466564 17869973 20889287, 9808254 18183032, 20889287 7584744 6886758, 3592639 10386980, 4637556 18183032, 17060154 20225002, 21878868Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No+*Modest change or conflicting reports. Although Calpain itself does not change in trauma, its products do change and are found in the blood and have been studied.Cairelli et al. Journal of Biomedical Semantics (2015) 6:Page Nelfinavir (Mesylate) 11 ofthe goal from an individual marker/single variable to a panel ameliorates the lack of specificity ?as long as the panel as a whole provides adequate sensitivity and specificity.Limitations of studya)These resulting data provide a clinically relevant hypothesis of potential mTBI biomarkers, which requires experimental validation. In our investigation into the validity of the results, it was evident that for some of the substances, especially the previously-studied biomarkers, the background TBI model-based studies have already been completed. For others, this is not the case and basic exploration in models may need to be pursued before moving towards clinical research. The current result set is limited to the uppermost extreme of node PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/17139194 connectedness and therefore potentially overlooks less investigated substances that appear in fewer publications. An elimination of the most frequent predications may enrich the result set for substances less familiar and thereby, potentially, more valuable. The current thresho.