Triglyceride is a Good Biomarker of Increased Injury Severity on a High Fat Diet Rat After Traumatic Brain Injury


Injury severity is correlated with poor prognosis after traumatic brain injury (TBI). It is not known whether triglycerides (TGs) or total cholesterol (TC) is good biomarker of increased injury of neuroinflammation and apoptosis in a high fat diet (HFD)-treated rat after TBI episodes. Five-week-old male Sprague–Dawley (SD) rats were fed a HFD for 8 weeks. The anesthetized male SD rats were divided into three sub-groups: sham-operated and TBI with 1.6 atm or with 2.4 atm fluid percussion injury (FPI). Cell infarction volume (triphenyltetrazolium chloride stain), tumor necrosis factor-alpha (TNF-α) expression in the microglia (OX42 marker) and astrocytes (Glial fibrillary acidic protein marker), TNF-α receptor expression in the neurons (TNFR1 and TNFR2 markers), and the extent of neuronal apoptosis (TUNEL marker) were evaluated by immunofluorescence, and the functional outcome was assessed by an inclined plane test. These tests were performed 72 h after TBI. Serum triglyceride and cholesterol levels were measured at 24, 48 and 72 h after TBI. The FPI with 2.4 atm significantly increased body weight loss, infarction volume, neuronal apoptosis and TNF-α expression in the microglia and astrocytes, and it decreased the maximum grasp degree and TNFR1 and TNFR2 expression in neurons at the 3rd day following TBI. The serum TG level was positively correlated with FPI force, infarction volume, Neu-N-TUNEL, GFAP-TNFα, and OX42-TNFα Simultaneously; the serum TG level was negatively correlated with Neu-N-TNFR1 and Neu-N-TNFR2. TG is a good biomarker of increased injury for neuroinflammation and apoptosis at the 3rd day after TBI in HFD rats.

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  1. 1.

    Li M, Zhao Z, Yu G, Zhang J (2016) Epidemiology of traumatic brain injury over the world: a systematic review. Austin Neurol Neurosci 1:1007

    Google Scholar 

  2. 2.

    Laaksonen DE, Niskanen L, Lakka HM, Lakka TA, Uusitupa M (2004) Epidemiology and treatment of the metabolic syndrome. Ann Med 36:332–346

    CAS  PubMed  Google Scholar 

  3. 3.

    O'Neill S, O'Driscoll L (2015) Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev 16:1–12

    CAS  PubMed  Google Scholar 

  4. 4.

    Hogan SR, Phan JH, Alvarado-Velez M, Wang MD, Bellamkonda RV, Fernandez FM, LaPlaca MC (2018) Discovery of lipidome alterations following traumatic brain injury via high-resolution metabolomics. J Proteome Res 17(6):2131–2143

    CAS  PubMed  Google Scholar 

  5. 5.

    Sparvero LJ, Amoscato AA, Kochanek PM, Pitt BR, Kagan VE, Bayär H (2010) Massspectrometry based oxidative lipidomics and lipid imaging: applications in traumatic brain injury. J Neurochem 115:1322–1336

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Yang W, Shi H, Zhang J, Shen Z, Zhou G, Hu M (2017) Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats. Lipids Health Dis 16(1):26

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Zhang D, Hu X, Qian L, O’Callaghan JP, Hong JS (2010) Astrogliosis in CNS pathologies: is there a role for microglia? Mol Neurobiol 41:232

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    Lim SW, Wang CC, Wang YH, Chio CC, Niu KC, Kuo JR (2013) Microglial activation induced by traumatic brain injury is suppressed by postinjury treatment with hyperbaric oxygen therapy. J Surg Res 184:1076–1084

    CAS  PubMed  Google Scholar 

  9. 9.

    Dong Y, Fischer R, Naudé PJ, Maier O, Nyakas C, Duffey M, Van der Zee EA, Dekens D, Douwenga W, Herrmann A, Guenzi E, Kontermann RE, Pfizenmaier K, Eisel UL (2016) Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration. Proc Natl Acad Sci USA 113:12304–12309

    CAS  PubMed  Google Scholar 

  10. 10.

    Probert L (2015) TNF and its receptors in the CNS: the essential, the desirable and the deleterious effects. Neuroscience 32:2–22

    Google Scholar 

  11. 11.

    Thirumangalakudi L, Prakasam A, Zhang R, Bimonte-Nelson H, Sambamurti K, Kindy MS, Bhat NR (2008) High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice. J Neurochem 106:475–485

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Pistell P, Morrison CD, Gupta S, Knight A, Keller JN, Ingram D (2010) Cognitive impairment following high fat diet consumption is associated with brain inflammation. J Neuroimmunol 219:25–32

    CAS  PubMed  Google Scholar 

  13. 13.

    Spagnuolo MS, Mollica MP, Maresca B, Cavaliere G, Cefaliello C, Trinchese G et al (2015) High fat diet and inflammation—modulation of haptoglobin level in rat brain. Front Cell Neurosci 9:479

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Kang DH, Heo RW, Yi CO, Kim H, Choin CH, Roh GS (2015) High fat diet—induced obesity exacerbates kainic acid-induced hippocampal cell death. BMC Neurosci 16:72

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Wu A, Molteni R, Ying Z, Gomez-Pinilla F (2003) A saturated-diet aggravates the Outcome of traumatic brain injury on hippocampal plasticity and cognitive function By reducing brain-derived neurotrophic factor. Neuroscience 119:365–375

    CAS  PubMed  Google Scholar 

  16. 16.

    Hoane MR, Swan AA, Herk SE (2011) The effects of a high-fat sucrose diet on functional outcome following cortical contusion injury in rat. Behav Brain Res 223:119–124

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Mychasiuk R, Hehar H, Ma I, Esser MJ (2015) Dietary intake alters behavioral recovery and gene expression profiles in the brain of juvenile rats that have experienced a concussion. Front Behav Neurosci 9:17

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Mychasiuk R, Hehar H, van Waes L, Esser MJ (2015) Diet, age, and prior injury status differentially alter behavioral outcomes following concussion in rats. Neurobiol Dis 73:1–11

    PubMed  Google Scholar 

  19. 19.

    Chong AJ, Wee HY, Chang CH, Chio CC, Kuo JR, Lim SW (2019) Effects of a high fat diet on neuroinflammation and apoptosis in acute stage after moderate traumatic brain injury in rats. Neurocrit Care.

    Article  PubMed  Google Scholar 

  20. 20.

    McIntosh TK, Vink R, Noble L et al (1989) Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience 28:233

    CAS  PubMed  Google Scholar 

  21. 21.

    Chuang TJ, Lin KC, Chio CC, Wang CC, Chang CP, Kuo JR (2012) Effects of secretome obtained from normoxia-preconditioned human mesenchymal stem cells in traumatic brain injury rats. J Trauma Acute Care Surg 73:1161–1167

    CAS  PubMed  Google Scholar 

  22. 22.

    Wang Y, Lin SZ, Chiou AL, Williams LR, Hoffer BJ (1997) Glial cell line-derived neurotrophic factor protects against ischemia-induced injury in the cerebral cortex. J Neurosci 17:4341–4348

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Koshinaga M, Katayama Y, Fukushima M (2000) Rapid and widespread microglial activation induced by traumatic brain injury in rat brain slices. J Neurotrauma 17:185–192

    CAS  PubMed  Google Scholar 

  24. 24.

    Mullen RJ, Buck CR, Smith AM (1992) Neu-N, a neuronal specific nuclear protein in vertebrates. Development 116:201–211

    CAS  PubMed  Google Scholar 

  25. 25.

    Bowman GL, Kaye JA, Quinn JF (2012) Dyslipidemia and blood-brain barrier integrity in Alzheimer's disease. Curr Gerontol Geriatr Res 2012:184042

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Sekaran H, Gan CY, Latiff AA, Harvey TM, Nazri LM, Hanapi NA, Azizi J, Yusof SR (2019) Changes in blood-brain barrier permeability and ultrastructure, and protein expression in a rat model of cerebral hypoperfusion. Brain Res Bull 152:63–73

    CAS  PubMed  Google Scholar 

  27. 27.

    Backs WA, Farr SA, Salameh TS, Niehoff ML, Rhea EM, Morley JE, Hanson AJ, Hansen KM, Craft S (2017) Triglyceride cross the blood-brain-barrier and induce central leptin and insulin receprot resistance. Int J Obes 231:381–397

    Google Scholar 

  28. 28.

    Jia J, Yan M, Lu Z, Sun M, He J, Xia C (2010) Regulated expression of pancreatic triglyceride lipase after rat traumatic brain injury. Mol Cell Biochem 335:127–136

    CAS  PubMed  Google Scholar 

  29. 29.

    Zhang J, Liu Q (2015) Cholesterol metabolism and homeostasis in the brain. Protein Cell 6:254–264

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Farr S, Taher J, Adeli K (2016) Central nervous system regulation of intestinal lipid and lipoprotein metabolism. Curr Opin Lipidol 27:1–7

    CAS  PubMed  Google Scholar 

  31. 31.

    Wang CC, Wee HY, Hu CY, Chio CC, Kuo JR (2018) The effects of memantine on glutamic receptor-associated nitrosative stress in a traumatic brain injury rat model. World Neurosurg 112:e719–e731

    PubMed  Google Scholar 

  32. 32.

    Lim SW, Sung KC, Shiue YL, Wang CC, Chio CC, Kuo JR (2017) Hyperbaric oxygen effects on depression-like behavior and neuroinflammation in traumatic brain injury rats. World Neurosurg 100:128–137

    PubMed  Google Scholar 

  33. 33.

    Conti AC, Raghupathi R, Trojanowski JQ, McIntosh TK (1998) Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post-traumatic period. J Neurosci 18:5663–5672

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Zhang L, Wang H (2018) Autophagy in traumatic brain injury: a new target for therapeutic intervention. Front Mol Neurosci 11:190

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Funakoshi T, Aki T, Tajiri M, Unuma K, Uemura K (2016) Necroptosis-like neuronal cell death caused by cellular cholesterol accumulation. J Biol Chem 291:25050–25065

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Banks WA (2012) Role of the blood–brain barrier in the evolution of feeding and cognition. Ann NY Acad Sci 1264:13–19

    CAS  PubMed  Google Scholar 

  37. 37.

    Karaoğlan A, Akdemir O, Cınar N, Cal MA, Kelten B, Uzun H, Colak A (2011) Correlation between leptin and pro-inflammatory cytokines in cortical contusion injury model. Ulus Travma Acil Cerrahi Derg 17:298–302

    PubMed  Google Scholar 

  38. 38.

    Martinez BI, Stabenfeldt SE (2019) Current trends in biomarker discovery and analysis tools for traumatic brain injury. J Biol Eng 13:16

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Palmisano BT, Zhu L, Ecke RH, Stafford JM (2018) Sex differences in lipid and lipoprotein metabolism. Mol Metab 15:45–55

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Yang W, Shi H, Zhang J, Shen Z, Zhou G, Hu M (2017) Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats. Lipids Health Dis 16:26

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Sheth SA, Iavarone AT, Liebeskind DS, Won SJ, Swanson RA (2015) Targeted lipid profiling discovers plasma biomarkers of acute brain injury. PLoS ONE 10:e0129735

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    McIntosh TK, Yu T, Gennarelli TA (1994) Alterations in regional brain catecholamine concentrations after experimental brain Iijury in the Rat. J Neurochem 63:1426–1433

    CAS  PubMed  Google Scholar 

  43. 43.

    Kunihara M, Oshima T (1983) Effects of epinephrine on plasma cholesterol levels in rats. J Lipid Res 24:639–644

    CAS  PubMed  Google Scholar 

  44. 44.

    Mahley RW (2016) Central nervous system lipoproteins: ApoE and regulation of cholesterol metabolism. Arterioscler Thromb Vasc Biol 36:1305–1315

    CAS  PubMed  PubMed Central  Google Scholar 

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The authors thank all of the researchers, especially Chiao-Ya Hu, who participated in this study.



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S-WL, H-XZ, H-YH, J-RK conceived and designed the experiments. H-XZ and J-RK performed the experiments. H-YH, C-HH and J-RK analyzed the data, C-HC and C-CC contributed reagents/materials/analysis tools, H-YH, J-RK wrote the paper.

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Correspondence to Jinn-Rung Kuo or Hsiao-Yue Wee.

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Kuo, J., Lim, S., Zheng, H. et al. Triglyceride is a Good Biomarker of Increased Injury Severity on a High Fat Diet Rat After Traumatic Brain Injury. Neurochem Res 45, 1536–1550 (2020).

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  • High fat diet
  • Total cholesterol
  • Triglycerides
  • Biomarker
  • Fluid percussion traumatic brain injury
  • Apoptosis
  • Tumor necrosis factor-alpha
  • Neuroinflammation