In many forensic cases, the existence of a traumatic brain injury (TBI) is an essential factor, and the determination of the survival time is nearly as important as the determination of whether or not a trauma exists. Since it is known that glucose uptake increases in injured brain cells in order to perpetuate the neuronal integrity, this study focuses on the pathomechanism of brain glucose supply via sodium/glucose cotransporters 1 and 2 (SGLT1, SGLT2) following traumatization. Human cerebrum tissue of male and female individuals who died following TBI was taken from the contusional and contralateral regions, as well as from individuals deceased due to cardiac arrest (control group). Total SGLT1 and SGLT2 protein expression was analyzed by immunoblotting comparing injured and non-injured tissue. The immunoreactivity in contusional cerebral cortex region began to increase 3 to 7 h following traumatization. We found that both SGLT1 and SGLT2 protein expression increased significantly 37 h post-injury compared to the control group. SGLT1 rose significantly at 52 h post-injury and peaked significantly at 72 h, while SGLT2 rose significantly at 52 and 72 h after injury. By compiling these data, we predict a standard operator via SGLT expression as a comparative expression assertion to determine post-injury survival time for unknown cases. Our result suggests that SGLT1 and SGLT2 protein expression may be useful in forensic practice as an effective target to analyze the existence of a TBI and to determine the time of the traumatization.
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Faul M, Coronado V (2015) Epidemiology of traumatic brain injury. Handb Clin Neurol 127:3–13. https://doi.org/10.1016/B978-0-444-52892-6.00001-5
Destatis (2017) Gesundheit - Todesursachen in Deutschland. https://www.destatis.de/DE/Publikationen/Thematisch/Gesundheit/Todesursachen/Todesursachen.html. Accessed 01 Apr 2018
Baumann H, Gauldie J (1994) The acute phase response. Immunol Today 15(2):74–80. https://doi.org/10.1016/0167-5699(94)90137-6
Wilcockson DC, Campbell SJ, Anthony DC, Perry VH (2002) The systemic and local acute phase response following acute brain injury. J Cereb Blood Flow Metab 22(3):318–326. https://doi.org/10.1097/00004647-200203000-00009
Ondruschka B, Schuch S, Pohlers D, Franke H, Dreßler J (2018) Acute phase response after fatal traumatic brain injury. Int J Legal Med 132(2):531–539. https://doi.org/10.1007/s00414-017-1768-2
Hausmann R, Kaiser A, Lang C, Bohnert M, Betz P (1999) A quantitative immunohistochemical study on the time-dependent course of acute inflammatory cellular response to human brain injury. Int J Legal Med 112(4):227–232
Hausmann R, Betz P (2000) The time course of the vascular response to human brain injury—an immunohistochemical study. Int J Legal Med 113(5):288–292
Huth A, Vennemann B, Fracasso T, Lutz-Bonengel S, Vennemann M (2013) Apparent versus true gene expression changes of three hypoxia-related genes in autopsy derived tissue and the importance of normalisation. Int J Legal Med 127(2):335–344. https://doi.org/10.1007/s00414-012-0787-2
Li D-R, Zhang F, Wang Y, Tan X-H, Qiao D-F, Wang HJ, Michiue T, Maeda H (2012) Quantitative analysis of GFAP- and S100 protein-immunopositive astrocytes to investigate the severity of traumatic brain injury. Leg Med (Tokyo) 14(2):84–92. https://doi.org/10.1016/j.legalmed.2011.12.007
Wang X, Brouillette MJ, Ayati BP, Martin JA (2015) A validated model of the pro- and anti-inflammatory cytokine balancing act in articular cartilage lesion formation. Front Bioeng Biotechnol 3:25. https://doi.org/10.3389/fbioe.2015.00025
Salvador E, Burek M, Förster CY (2015) Stretch and/or oxygen glucose deprivation (OGD) in an in vitro traumatic brain injury (TBI) model induces calcium alteration and inflammatory cascade. Front Cell Neurosci 9:323. https://doi.org/10.3389/fncel.2015.00323
Orihara Y, Nakasono I (2002) Induction of apolipoprotein E after traumatic brain injury in forensic autopsy cases. Int J Legal Med 116(2):92–98. https://doi.org/10.1007/s00414-001-0265-8
Dressler J, Hanisch U, Kuhlisch E, Geiger KD (2007) Neuronal and glial apoptosis in human traumatic brain injury. Int J Legal Med 121(5):365–375. https://doi.org/10.1007/s00414-006-0126-6
Kukacka J, Vajtr D, Huska D, Průsa R, Houstava L et al (2006) Blood metallothionein, neuron specific enolase, and protein S100B in patients with traumatic brain injury. Neuro Endocrinol Lett 27(Suppl 2):116–120
Schrag B, Roux-Lombard P, Schneiter D, Vaucher P, Mangin P, Palmiere C (2012) Evaluation of C-reactive protein, procalcitonin, tumor necrosis factor alpha, interleukin-6, and interleukin-8 as diagnostic parameters in sepsis-related fatalities. Int J Legal Med 126(4):505–512. https://doi.org/10.1007/s00414-011-0596-z
Pandey GN, Rizavi HS, Zhang H, Ren X (2018) Abnormal gene and protein expression of inflammatory cytokines in the postmortem brain of schizophrenia patients. Schizophr Res 192:247–254. https://doi.org/10.1016/j.schres.2017.04.043
Nagatsu T, Sawada M (2005) Inflammatory process in Parkinson’s disease: role for cytokines. CPD 11(8):999–1016. https://doi.org/10.2174/1381612053381620
Thal SC, Neuhaus W (2014) The blood-brain barrier as a target in traumatic brain injury treatment. Arch Med Res 45(8):698–710. https://doi.org/10.1016/j.arcmed.2014.11.006
Bergsneider M, Hovda DA, Shalmon E, Kelly DF, Vespa PM, Martin NA, Phelps ME, McArthur DL, Caron MJ, Kraus JF, Becker DP (1997) Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg 86(2):241–251. https://doi.org/10.3171/jns.1997.86.2.0241
Salvador E, Neuhaus W, Foerster C (2013) Stretch in brain microvascular endothelial cells (cEND) as an in vitro traumatic brain injury model of the blood brain barrier. J Vis Exp 80:e50928. https://doi.org/10.3791/50928
Sebastian Wais (2012) The role of the glucose transporters after traumatic brain injury and their influence on the development of secondary brain edema. Dissertation. Julius-Maximilians-University Wuerzburg, Wuerzburg, Germany
Morrison B, Elkin BS, Dollé J-P, Yarmush ML (2011) In vitro models of traumatic brain injury. Annu Rev Biomed Eng 13:91–126. https://doi.org/10.1146/annurev-bioeng-071910-124706
Vemula S, Roder KE, Yang T, Bhat GJ, Thekkumkara TJ, Abbruscato TJ (2009) A functional role for sodium-dependent glucose transport across the blood-brain barrier during oxygen glucose deprivation. J Pharmacol Exp Ther 328(2):487–495. https://doi.org/10.1124/jpet.108.146589
Harada S, Yamazaki Y, Nishioka H, Tokuyama S (2013) Neuroprotective effect through the cerebral sodium-glucose transporter on the development of ischemic damage in global ischemia. Brain Res 1541:61–68. https://doi.org/10.1016/j.brainres.2013.09.041
Elfeber K, Köhler A, Lutzenburg M, Osswald C, Galla H-J et al (2004) Localization of the Na+-D-glucose cotransporter SGLT1 in the blood-brain barrier. Histochem Cell Biol 121(3):201–207. https://doi.org/10.1007/s00418-004-0633-9
Sajja RK, Prasad S, Cucullo L (2014) Impact of altered glycaemia on blood-brain barrier endothelium: an in vitro study using the hCMEC/D3 cell line. Fluids Barriers CNS 11(1):8. https://doi.org/10.1186/2045-8118-11-8
Panayotova-Heiermann M, Eskandari S, Turk E, Zampighi GA, Wright EM (1997) Five transmembrane helices form the sugar pathway through the Na+/glucose cotransporter. J Biol Chem 272:20324–20327. https://doi.org/10.1074/jbc.272.33.20324
Tyagi NK, Goyal P, Kumar A, Pandey D, Siess W, Kinne RKH (2005) High-yield functional expression of human sodium/d-glucose cotransporter1 in Pichia pastoris and characterization of ligand-induced conformational changes as studied by tryptophan fluorescence. Biochem J 44:15514–15524. https://doi.org/10.1021/bi051377q
Sasseville LJ, Morin M, Coady MJ, Blunck R, Lapointe J-Y (2016) The human sodium-glucose cotransporter (hSGLT1) is a disulfide-bridged homodimer with a re-entrant C-terminal loop. PLoS One 11:e0154589. https://doi.org/10.1371/journal.pone.0154589
Kumagai AK, Dwyer KJ, Pardridge WM (1994) Differential glycosylation of the GLUT1 glucose transporter in brain capillaries and choroid plexus. Biochim Biophys Acta 1193:24–30. https://doi.org/10.1016/0005-2736(94)90328-X
Poppe R, Karbach U, Gambaryan S, Wiesinger H, Lutzenburg M et al (1997) Expression of the Na+-D-glucose cotransporter SGLT1 in neurons. J Neurochem 69(1):84–94. https://doi.org/10.1046/j.1471-4159.1997.69010084.x
Huang ZG, Xue D, Preston E, Karbalai H, Buchan AM (1999) Biphasic opening of the blood-brain barrier following transient focal ischemia: effects of hypothermia. Can J Neurol Sci J 26:298–304. https://doi.org/10.1017/S0317167100000421
Belayev L, Busto R, Zhao W, Ginsberg MD (1996) Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res 739:88–96. https://doi.org/10.1016/S0006-8993(96)00815-3
Rosenberg GA, Estrada EY, Dencoff JE (1998) Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke 29:2189–2195. https://doi.org/10.1161/01.STR.29.10.2189
Perrett CW, Marchbanks RM, Whatley SA (1988) Characterisation of messenger RNA extracted post-mortem from the brains of schizophrenic, depressed and control subjects. J Neurol Neurosurg Psychiatry 51(3):325–331. https://doi.org/10.1136/jnnp.51.3.325
Barton AJL, Pearson RCA, Najlerahim A, Harrison PJ (1993) Pre- and postmortem influences on brain RNA. J Neurochem 61(1):1–11. https://doi.org/10.1111/j.1471-4159.1993.tb03532.x
Davidsson P, Paulson L, Hesse C, Blennow K, Nilsson CL (2001) Proteome studies of human cerebrospinal fluid and brain tissue using a preparative two-dimensional electrophoresis approach prior to mass spectrometry. Proteomics 1(3):444–452. https://doi.org/10.1002/1615-9861(200103)1:3<444:AID-PROT444>3.0.CO;2-Q
de Paepe ME, Mao Q, Huang C, Zhu D, Jackson CL, Hansen K (2002) Postmortem RNA and protein stability in perinatal human lungs. Diagn Mol Pathol 11(3):170–176
Blair JA, Wang C, Hernandez D, Siedlak SL, Rodgers MS, Achar RK, Fahmy LM, Torres SL, Petersen RB, Zhu X, Casadesus G, Lee HG (2016) Individual case analysis of postmortem interval time on brain tissue preservation. PLoS One 11(3):e0151615. https://doi.org/10.1371/journal.pone.0151615
We thank Malgorzata Burek, Elizabeth Wilken, and Anja Neuhoff for their excellent technical assistance and all other members of the Laboratory at the Department of Anesthesia and Critical Care for their comments and support.
The authors received no specific funding for this work.
Conflict of interest
The authors declare that they have no conflict of interest.
The ethical committee of Julius-Maximilians-University Wuerzburg reviewed and approved all aspects of this study (ethical approval number 203/15).
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Oerter, S., Förster, C. & Bohnert, M. Validation of sodium/glucose cotransporter proteins in human brain as a potential marker for temporal narrowing of the trauma formation. Int J Legal Med 133, 1107–1114 (2019). https://doi.org/10.1007/s00414-018-1893-6
- Traumatic brain injury
- Sodium-glucose transporters