Advertisement

Cellular and Molecular Neurobiology

, Volume 34, Issue 6, pp 797–804 | Cite as

Anti-apoptotic and Anti-oxidative Roles of Quercetin After Traumatic Brain Injury

  • Tao Yang
  • Bin Kong
  • Jian-Wen GuEmail author
  • Yong-Qin Kuang
  • Lin Cheng
  • Wen-Tao Yang
  • Xun Xia
  • Hai-Feng Shu
Rapid Communication

Abstract

Experimental studies have demonstrated significant secondary damage (including cell apoptosis, blood–brain barrier disruption, inflammatory responses, excitotoxic damage, and free radical production) after traumatic brain injury (TBI). Quercetin is a natural flavonoid found in high quantities in fruits and vegetables, and may be a potential antioxidant and free radical scavenger. The purpose of this study was to determine the effects of quercetin on TBI-induced upregulation of oxidative stress, inflammation, and apoptosis in adult Sprague–Dawley rats. Animals were subjected to Feeney’s weight-drop injury, thus inducing the parietal contusion brain injury model. Quercetin was administered (30 mg/kg intraperitoneal injection) 0, 24, 48, and 72 h after TBI. Quercetin reduced cognitive deficits, the number of TUNEL- and ED-1-positive cells, the protein expressions of Bax and cleaved-caspase-3 proteins, and the levels of TBARS and proinflammatory cytokines, and increased the activity of antioxidant enzymes (GSH-Px, SOD, and CAT) at 1 week after TBI. Our results suggest that in TBI rats, quercetin improves cognitive function owing to its neuroprotective action via the inhibition of oxidative stress, leading to a reduced inflammatory response, thereby reducing neuronal death.

Keywords

Traumatic brain injury Quercetin Oxidative stress Inflammation Apoptosis 

Notes

Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (Nos. 81071037 and 81271395).

References

  1. Barone FC, Feuerstein GZ (1999) Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19:819–834PubMedCrossRefGoogle Scholar
  2. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624PubMedCentralPubMedCrossRefGoogle Scholar
  3. Bethea JR, Dietrich WD (2002) Targeting the host inflammatory response in traumatic spinal cord injury. Curr Opin Neurol 15:355–360PubMedCrossRefGoogle Scholar
  4. Cho JY, Kim IS, Jang YH, Kim AR, Lee SR (2006) Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia. Neurosci Lett 404:330–335PubMedCrossRefGoogle Scholar
  5. Dok-Go H, Lee KH, Kim HJ, Lee EH, Lee J, Song YS, Lee YH, Jin C, Lee YS, Cho J (2003) Neuroprotective effects of antioxidative flavonoids, quercetin, (+)-dihydroquercetin and quercetin 3-methyl ether, isolated from Opuntia ficus-indica var. Saboten. Brain Res 965:130–136PubMedCrossRefGoogle Scholar
  6. Fujimoto T, Nakamura T, Ikeda T, Taoka Y, Takagi K (2000) Effects of EPC-K1 on lipid peroxidation in experimental spinal cord injury. Spine 25:24–29PubMedCrossRefGoogle Scholar
  7. Gogel S, Gubernator M, Minger SL (2011) Progress and prospects: stem cells and neurological diseases. Gene Ther 18:1–6PubMedCrossRefGoogle Scholar
  8. Imam SZ, Ali SF (2000) Selenium, an antioxidant, attenuates methamphetamine-induced dopaminergic toxicity and peroxynitrite generation. Brain Res 855:186–191PubMedCrossRefGoogle Scholar
  9. Inci S, Ozcan OE, Kilinc K (1998) Time-level relationship for lipid peroxidation and the protective effect of alpha-tocopherol in experimental mild and severe brain injury. Neurosurgery 43:330–335 (discussion 335–336)PubMedCrossRefGoogle Scholar
  10. Kahraman S, Duz B, Kayali H, Korkmaz A, Oter S, Aydin A, Sayal A (2007) Effects of methylprednisolone and hyperbaric oxygen on oxidative status after experimental spinal cord injury: a comparative study in rats. Neurochem Res 32:1547–1551PubMedCrossRefGoogle Scholar
  11. Kelso ML, Wehner JM, Collins AC, Scheff SW, Pauly JR (2006) The pathophysiology of traumatic brain injury in alpha7 nicotinic cholinergic receptor knockout mice. Brain Res 1083:204–210PubMedCrossRefGoogle Scholar
  12. Kinaci MK, Erkasap N, Kucuk A, Koken T, Tosun M (2012) Effects of quercetin on apoptosis, NF-kappaB and NOS gene expression in renal ischemia/reperfusion injury. Exp Ther Med 3:249–254PubMedCentralPubMedGoogle Scholar
  13. Lee JK, Kwak HJ, Piao MS, Jang JW, Kim SH, Kim HS (2011) Quercetin reduces the elevated matrix metalloproteinases-9 level and improves functional outcome after cerebral focal ischemia in rats. Acta Neurochir 153:1321–1329 (discussion 1329)PubMedCrossRefGoogle Scholar
  14. Lu J, Goh SJ, Tng PY, Deng YY, Ling EA, Moochhala S (2009) Systemic inflammatory response following acute traumatic brain injury. Front Biosci (Landmark Ed) 14:3795–3813Google Scholar
  15. Mahmoud MF, Hassan NA, El Bassossy HM, Fahmy A (2013) Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: effect on low grade inflammation. PLoS ONE 8:e63784PubMedCentralPubMedCrossRefGoogle Scholar
  16. Pannu R, Barbosa E, Singh AK, Singh I (2005) Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats. J Neurosci Res 79:340–350PubMedCrossRefGoogle Scholar
  17. Pearse D, Jarnagin K (2010) Abating progressive tissue injury and preserving function after CNS trauma: the role of inflammation modulatory therapies. Curr Opin Investig Drugs 11:1207–1210Google Scholar
  18. Popovich PG, Wei P, Stokes BT (1997) Cellular inflammatory response after spinal cord injury in Sprague–Dawley and Lewis rats. J Comp Neurol 377:443–464PubMedCrossRefGoogle Scholar
  19. Sande A, West C (2010) Traumatic brain injury: a review of pathophysiology and management. J Vet Emerg Crit Care (San Antonio) 20:177–190CrossRefGoogle Scholar
  20. Schmidley JW (1990) Free radicals in central nervous system ischemia. Stroke 21:1086–1090PubMedCrossRefGoogle Scholar
  21. Schultke E, Kendall E, Kamencic H, Ghong Z, Griebel RW, Juurlink BH (2003) Quercetin promotes functional recovery following acute spinal cord injury. J Neurotrauma 20:583–591PubMedCrossRefGoogle Scholar
  22. Schultke E, Kamencic H, Zhao M, Tian GF, Baker AJ, Griebel RW, Juurlink BH (2005) Neuroprotection following fluid percussion brain trauma: a pilot study using quercetin. J Neurotrauma 22:1475–1484PubMedCrossRefGoogle Scholar
  23. Serarslan Y, Yonden Z, Ozgiray E, Oktar S, Guven EO, Sogut S, Yilmaz N, Yurtseven T (2010) Protective effects of tadalafil on experimental spinal cord injury in rats. J Clin Neurosci 17:349–352PubMedCrossRefGoogle Scholar
  24. Song Y, Liu J, Zhang F, Zhang J, Shi T, Zeng Z (2013) Antioxidant effect of quercetin against acute spinal cord injury in rats and its correlation with the p38MAPK/iNOS signaling pathway. Life Sci 92:1215–1221PubMedCrossRefGoogle Scholar
  25. Stevens MJ, Obrosova I, Cao X, Van Huysen C, Greene DA (2000) Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy. Diabetes 49:1006–1015PubMedCrossRefGoogle Scholar
  26. Talmadge RJ, Roy RR, Caiozzo VJ, Edgerton VR (2002) Mechanical properties of rat soleus after long-term spinal cord transection. J Appl Physiol (1985) 93:1487–1497Google Scholar
  27. Wang GH, Zhang XG, Jiang ZL, Li X, Peng LL, Li YC, Wang Y (2010) Neuroprotective effects of hyperbaric oxygen treatment on traumatic brain injury in the rat. J Neurotrauma 27:1733–1743Google Scholar
  28. Yan ZJ, Zhang P, Hu YQ, Zhang HT, Hong SQ, Zhou HL, Zhang MY, Xu RX (2013) Neural stem-like cells derived from human amnion tissue are effective in treating traumatic brain injury in rat. Neurochem Res 38:1022–1033PubMedCrossRefGoogle Scholar
  29. Yao RQ, Qi DS, Yu HL, Liu J, Yang LH, Wu XX (2012) Quercetin attenuates cell apoptosis in focal cerebral ischemia rat brain via activation of BDNF-TrkB-PI3 K/Akt signaling pathway. Neurochem Res 37:2777–2786PubMedCrossRefGoogle Scholar
  30. Ziebell JM, Morganti-Kossmann MC (2010) Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurotherapeutics 7:22–30PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Tao Yang
    • 1
    • 2
  • Bin Kong
    • 1
    • 2
  • Jian-Wen Gu
    • 1
    Email author
  • Yong-Qin Kuang
    • 1
  • Lin Cheng
    • 1
  • Wen-Tao Yang
    • 1
  • Xun Xia
    • 1
    • 2
  • Hai-Feng Shu
    • 1
  1. 1.Department of NeurosurgeryChengdu Military General HospitalChengduChina
  2. 2.Third Military Medical UniversityChongqingChina

Personalised recommendations