Postconcussion Syndrome: A Review of Pathophysiology and Potential Nonpharmacological Approaches to Treatment

References

• . Guerrero JL, Thurman DJ, Sniezek JE. Emergency department visits associated with traumatic brain injury: United States, 1995–1996. Brain Inj. 2000; 14(2):181–186
   PubMed Web of Science ®Google Scholar
• . Maroon JC, Field M, Lovell M, Collins M, Bost J. The evaluation of athletes with cerebral concussion. Clin Neurosurg. 2002; 49:319–332
   PubMedGoogle Scholar
• . Hoge CW, Goldberg HM, Castro CA. Care of war veterans with mild traumatic brain injury: Flawed perspectives. N Engl J Med. 2009; 360(16):1588–1591
   PubMed Web of Science ®Google Scholar
• . Tator CH. Concussions are brain injuries and should be taken seriously. Can J Neurol Sci. 2009; 36:269–270
   PubMedGoogle Scholar
• . Larrabee GJ. Neuropsychological outcome, post concussion symptoms, and forensic considerations in mild closed head trauma. Semin Clin Neuropsychiatry. 1997; 2(3):196–206
   PubMedGoogle Scholar
• . Alexander MP. Mild traumatic brain injury: Pathophysiology, natural history, and clinical management. Neurology. 1995; 45(7):1253–1260
   PubMed Web of Science ®Google Scholar
• . McCullagh S, Feinstein A. Outcome after mild traumatic brain injury: An examination of recruitment bias. J Neurol Neurosurg Psychiatry. 2003; 74(1):39–43
   PubMed Web of Science ®Google Scholar
• . Satz PS, Alfano MS, Light RF, . Persistent post-concussive syndrome: A proposed methodology and literature review to determine the effects, if any, of mild head and other bodily injury. J Clin Exp Neuropsychol. 1999; 21(5):620–628
   PubMed Web of Science ®Google Scholar
• . Kashluba S, Casey JE, Paniak C. Evaluating the utility of ICD-10 diagnostic criteria for post-concussion syndrome following mild traumatic brain injury. J Int Neuropsychol Soc. 2006; 12(1):111–118
   PubMed Web of Science ®Google Scholar
• . World Health Organization. International Statistical Classification of Disease and Related Health Problems 10th Revision (ICD-10):postconcussional syndrome. http://www.who.int/occupational_health/publications/en/oehicd10.pdf. Published 1999. Accessed December 17, 2012
   Google Scholar
• . Molière. The Imaginary Invalid. 1673
   Google Scholar
• . McCrory P. Should we treat concussion pharmacologically? Br J Sports Med. 2002; 36:3–5
   PubMedGoogle Scholar
• . Kushner DS. Mild traumatic brain injury: Toward understanding manifestations and treatment. Arch Int Med. 1998; 158(15):1617–1624
   PubMed Web of Science ®Google Scholar
• . Ryan LM, Warden DL. Post concussion syndrome. Int Rev Psychiatry. 2003; 15(4):310–316
   PubMed Web of Science ®Google Scholar
• . Collie A, Makdissi M, Maruff P, Bennell K, McCrory P. Cognition in the days following concussion: Comparison of symptomatic versus asymptomatic athletes. J Neurol Neurosurg Psychiatry. 2006; 77(2):241–245
   PubMed Web of Science ®Google Scholar
• . Topal NB, Hakyemez B, Erdogan C, . MR imaging in the detection of diffuse axonal injury with mild traumatic brain injury. Neurol Res. 2008; 30(9):974–978
   PubMed Web of Science ®Google Scholar
• . van der Naalt J, Hew JM, van Zomeren AH, Sluiter WJ, Minderhoud JM. Computed tomography and magnetic resonance imaging in mild to moderate head injury: Early and late imaging related to outcome. Ann Neurol. 1999; 46(1):70–78
   PubMedGoogle Scholar
• . Voller B, Benke T, Benedetto K, Schnider P, Auff E, Aichner F. Neuropsychological, MRI and EEG findings after very mild traumatic brain injury. Brain Inj. 1999; 13(10):821–827
   PubMed Web of Science ®Google Scholar
• . Arundine M, Tymianski M. Molecular Mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci. 2004; 61:657–668
   PubMed Web of Science ®Google Scholar
• . Blaylock RL, Maroon JC. Immunoexcitotoxicity as a central mechanism in chronic traumatic encephalopathy—a unifying hypothesis. Surg Neurol Int. 2011; 2:107
   PubMedGoogle Scholar
• . Luo XG, Ding JQ, Chen SD. Microglia in the aging brain: Relevance to neurodegeneration. Mol Neurodegen. 2010; 5:12
   PubMedGoogle Scholar
• . Klegeris A, McGeer PL. Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory agents in the treatment of neurodegenerative disease. Curr Alzheimer Res. 2005; 2(3):355–365
   PubMedGoogle Scholar
• . Politis M, Su P, Piccini P. Imaging of microglia in patients with neurodegenerative diseases. Front Pharmacol. 2012; 3:96
   PubMedGoogle Scholar
• . Wilson CJ, Finch CE, Cohen HJ. Cytokines and cognition—the case for a head-to-toe inflammatory paradigm. J Am Geriatr Soc. 2002; 50(12):2041–2056
   PubMed Web of Science ®Google Scholar
• . Mackenzie IR, Munoz DG. Nonsteroidal anti-inflammatory drug use and alzheimer-type pathology in aging. Neurology. 1998; 50(4):986–990
   PubMedGoogle Scholar
• . Etminan M, Gill S, Samii A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: Systematic review and meta-analysis of observational studies. BMJ. 2003; 327:128
   PubMed Web of Science ®Google Scholar
• . Petraglia AL, Maroon JC, Bailes JE. From the field of play to the field of combat: A review of the pharmacological management of concussion. Neurosurgery. 2012; 70(6)1520–1533
   PubMedGoogle Scholar
• . Blaylock RL, Maroon JC. Natural plant products and extracts that reduce immunoexcitotoxicity-associated neurodegeneration and promote repair within the central nervous system. Surg Neurol Int. 2012; 3:1–19
   PubMedGoogle Scholar
• . Singh G. Gastrointestinal complications of prescription and over-the-counter nonsteroidal anti-inflammatory drugs: A view from the ARA-MIS database. Arthritis, Rheumatism, and Aging Medical Information System. Am J Ther. 2000; 7(2):115–121
   PubMedGoogle Scholar
• . Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med. 1999; 340(24)1888–1899
   PubMed Web of Science ®Google Scholar
• . Maroon JC, Bost JW, Maroon A. Natural anti-inflammatory agents for pain relief. Surg Neurol Int. 2010; 1:80
   PubMedGoogle Scholar
• . Curtis CL, Hughes CE, Flannery CR, Little CB, Harwood JL, Caterson B. N-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. J Biol Chem. 2000; 275(2):721–724
   PubMedGoogle Scholar
• . Curtis CL, Rees SG, Little CB, . Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids. Arthritis Rheum. 2002; 46(6):1544–1553
   PubMedGoogle Scholar
• . Calder PC. N-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr. 2006; 83( 6 suppl):1505S–1519S
   PubMed Web of Science ®Google Scholar
• . Curtis CL, Harwood JL, Dent CM, Caterson B. Biological basis for the benefit of nutraceutical supplementation in arthritis. Drug Discov Today. 2004; 9(4):165–172
   PubMed Web of Science ®Google Scholar
• . Daviglus ML, Stamler J, Orencia AJ, . Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997; 336(15):1046–1053
   PubMed Web of Science ®Google Scholar
• . Haqqi TM, Anthony DD, Gupta S, . Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Natl Acad Sci U SA. 1999; 96(8):4524–4529
   PubMed Web of Science ®Google Scholar
• . Peng Q, Wei Z, Lau BH. Pycnogenol inhibits tumor necrosis factor-a-induced nuclear factor kappa B activation and adhesion molecule expression in human vascular endothelial cells. Cell Mol Life Sci. 2000; 57(5):834–841
   PubMed Web of Science ®Google Scholar
• . Bernstein JE, Bickers DR, Dahl MV, Roshal JY. Treatment of chronic postherpetic neuralgia with topical capsaicin. A preliminary study. J Am Acad Dermatol. 1987; 17(1):93–96
   PubMedGoogle Scholar
• . Solomin SD, McMurray JJ, Pfeffer MA, . Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005; 352(11):1071–1080
   PubMedGoogle Scholar
• . Maroon JC, Bost JW. Omega-3 fatty acids (fish oil) as an antiinflammatory: An alternative to nonsteriodal anti-inflammatory drugs for discogenic pain. Surg Neurol. 2006; 65(4):326–331
   PubMedGoogle Scholar
• . Harris WS, von Schacky C. The Omega-3 Index: A new risk factor for death from coronary artery disease? Prev Med. 2004; 39(1):212–220
   PubMed Web of Science ®Google Scholar
• . Maroon JC, Bost JW, Borden MK, Lorenz KM, Ross NA. Natural anti-inflammatory agents for pain relief in athletes. Neurosurg Focus. 2006; 21(4):E11
   PubMedGoogle Scholar
• . Endres S, Ghorbani R, Kelley VE, . The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med. 1989; 320(5):265–271
   PubMed Web of Science ®Google Scholar
• . Mayer K, Meyer S, Reinholz-Muhly M, . Short-time infusion of fish oil-based lipid emulsions, approved for parenteral nutrition, reduces monocyte proinflammatory cytokine generation and adhesive interaction with endothelium in humans. J Immunol. 2003; 171(9):4837–4843
   PubMedGoogle Scholar
• . Lonergan PE, Martin DS, Horrobin DF, Lynch MA. Neuroprotective actions of eicosapentaenoic acid on lipopolysaccharide-induced dysfunction in rat hippocampus. J Neurochem. 2004; 91(1):20–29
   PubMedGoogle Scholar
• . Ruff CB, Trinkhaus E, Holliday TW. Body mass and encephalisation in Pleistocene Homo. Nature. 1997; 387(6629):173–176
   PubMed Web of Science ®Google Scholar
• . Leonard WR, Robertson ML. Evolutionary perspective on human nutrition: The influence of brain and body size on diet and metabolism. Am J Hum Biol. 1994; 6:77–88
   PubMed Web of Science ®Google Scholar
• . Aiello LC, Wheeler P. The expensive tissue hypothesis: The brain and the digestive system in human and primate evolution. Curr Anthropol. 1995; 36(2):199–222
   Web of Science ®Google Scholar
• . Crawford MA. The role of dietary fatty acids in biology: Their place in the evolution of the human brain. Nutr Rev. 1992; 50(4 pt 2):3–11
   PubMedGoogle Scholar
• . Cordain L, Watkins BA, Mann NJ. Fatty acid composition and energy density of foods available to Africanhominids. World Rev Nutr Diet. 2001; 90:144–161
   PubMedGoogle Scholar
• . Bailes JE, Mills JD. Docosahexaenoic acid reduces traumatic axonal injury in a rodent head injury model. J Neurotrauma. 2010; 27(9):1617–1624
   PubMed Web of Science ®Google Scholar
• . Petraglia AL, Winkler EA, Bailes JE. Stuck at the bench: Potential natural neuroprotective compounds for concussion. Surg Neurol Int. 2011; 2:146
   PubMedGoogle Scholar
• . Wang X, Zhao X, Mao ZY, Wang XM, Liu ZL. Neuroprotective effect of docosahexaenoic acid on glutamate-induced cytotoxicity in rat hippocampal cultures. Neuroreport. 2003; 14(18):2457–2461
   PubMed Web of Science ®Google Scholar
• . Bazan NG, Marcheselli VL, Cole-Edwards K. Brain response to injury and neurodegeneration: Endogenour neuroprotective signaling. Ann N Y Acad Sci. 2005; 1053:137–147
   PubMed Web of Science ®Google Scholar
• . Lu DY, Tsao YY, Leung YM, Su KP. Docosahexaenoic acid suppresses neuroinflammatory responses and induces heme oxygenase-1 expression in BV-2 microglia: Implications of antidepressant effects for omega-3 fatty acids. Neuropsychopharmacology. 2010; 35(11):2238–2248
   PubMed Web of Science ®Google Scholar
• . Hogyes E, Nyakas C, Kiliaan A, Farkas T, Penke B, Luiten PG. Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats. Neuroscience. 2003; 119(4):999–1012
   PubMedGoogle Scholar
• . Strokin M, Chechneva O, Reymann KG, Reiser G. Neuroprotection of rat hippocampal slices exposed to oxygen-glucose deprivation by enrichment with docosahexaenoic acid and by inhibition of hydrolysis of docosahexaenoic acid-containing phospholipids by calcium independent phospholipase A2. Neuroscience. 2006; 140(2):547–553
   PubMedGoogle Scholar
• . Menard C, Patenaude C, Gagne AM, Massicotte G. AMPA receptor-mediated cell death is reduced by docosahexaenoic acid but not by eicosapentaenoic acid in area CA1 of hippocampal slice cultures. J Neurosci Res. 2009; 87(4):876–886
   PubMed Web of Science ®Google Scholar
• . Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem. 2004; 90(4):979–988
   PubMed Web of Science ®Google Scholar
• . Cao D, Xue R, Xu J, Liu Z. Effects of docosahexaenoic acid on the survival and neurite outgrowth of rat cortical neurons in primary cultures. J Nutr Biochem. 2005; 16(9):538–546
   PubMedGoogle Scholar
• . Robson LG, Dyall S, Sidloff D, Michael-Titus AT. Omega-3 polyunsaturated fatty acids increase the neurite outgrowth of rat sensory neurones throughout development and in aged animals. Neurobiol Aging. 2010; 31(4):678–687
   PubMed Web of Science ®Google Scholar
• . Bacchetta J, Ranchin B, Dubourg L, Cochat P. Vitamin D revisited: A cornerstone of health? Arch Pediatr. 2010; 17(12):1687–1695
   PubMedGoogle Scholar
• . Petchy WG, Hickman IJ, Duncan E, . The role of 25-hydroxyvitamin d deficiency in promoting insulin resistance and inflammation in patients with chronic kidney disease: A randomized controlled trial. BMC Nephrol. 2009; 10:41
   PubMedGoogle Scholar
• . Guillot X, Semerano L, Saidenberg-Kermanac'h N, Falgarone G, Boissier MC. Vitamin D and inflammation. Joint Bone Spine. 2010; 77(6):552–557
   PubMed Web of Science ®Google Scholar
• . Cekic M, Sayeed I, Stein DG. Combination treatment with progesterone and vitamin D hormone may be more effective than monotherapy for nervous system injury and disease. Front Neuroendocrinol. 2009; 30(2):158–172
   PubMed Web of Science ®Google Scholar
• . Eelen G, Verlinden L, van Camp M, . The effects of 1 alpha, 25-dihydroxyvitamin D3 on the expression of DNA replication genes. J Bone Miner Res. 2004; 19(1):133–146
   PubMedGoogle Scholar
• . Losem-Heinrichs E, Görg B, Redecker C, . 1 alpha, 25-dihydroxyvitamin D3 in combination with 17 beta-estradiol reduces the cortical expression of heat shock protein-27 following experimentally induced focal cortical ischemia in rats. Arch Biochem Biophys. 2005; 439(1):70–79
   PubMedGoogle Scholar
• . Losem-Heinrichs E, Görg B, Schleicher A, . A combined treatment with 1alpha, 25-dihydroxyvitamin D3 and 17 beta-estradiol reduces the expression of heat shock protein-32 following cerebral cortical ischemia. J Steroid Biochem Mol Biol. 2004; 89–90(1–5):371–374
   PubMedGoogle Scholar
• . Nemere I, Farach-Carson MC. Membrane receptors for steroid hormones: A case for specific cell surface binding sites for vitamin D metabolites and estrogens. Biochem Biophys Res Comm. 1998; 248(3):443–449
   PubMedGoogle Scholar
• . Stein DG. Progesterone exerts neuroprotective effects after brain injury. Brain Res Rev. 2008; 57(2):386–397
   PubMedGoogle Scholar
• . Atif F, Sayeed I, Ishart T, Stein DG. Progesterone with vitamin D affords better neuroprotection against excitotoxicity in cultured cortical neurons than progesterone alone. Mol Med. 2009; 15(9–10):328–336
   PubMed Web of Science ®Google Scholar
• . Cekic M, Cutler SM, Van Landingham JW, Stein DG. Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats. Neurobiol Aging. 2011; 32(5):864–874
   PubMed Web of Science ®Google Scholar
• . Cekic M, Stein DG. Traumatic brain injury and aging: Is a combination of progesterone and vitamin D hormone a simple solution to a complex problem? Neurotherapeutics. 2010; 7(1):81–90
   PubMed Web of Science ®Google Scholar
• . Nilsen J, Brinton RD. Impact of progestins on estrogen-induced neuroprotection synergy by progesterone and 19-norprogesterone and antagonism by medroxyprogesterone acetate. Endocrinology. 2002; 143(1):205–212
   PubMed Web of Science ®Google Scholar
• . Nilsen J, Brinton RD. Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling. Proc Natl Acad Sci U S A. 2003; 100(18):10506–10511
   PubMedGoogle Scholar
• . Brewer LD, Thibault V, Chen KC, Langub MC, Landfield PW, Porter NM. Vitamin D hormone confers neuroprotection in parallel with down-regulation of L-type calcium channels in hippocampal neurons. J Neurosci. 2001; 21(1):98–108
   PubMed Web of Science ®Google Scholar
• . Schleithoff SS, Zitterman A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: A double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2006; 83(4):754–759
   PubMed Web of Science ®Google Scholar
• . Licasstro DL, Scola L, Chiapelli M, . Interleukin-10 promoter polymorphism in sporatic Alzheimer's disease. Genes Immun. 2003; 4(3):234–238
   PubMedGoogle Scholar
• . Khoo AL, Chai LY, Koenen HJ, . 1,25-dihydroxyvitamin D3 modulates cytokine poroduction induced by Candida albicans: Impact of seasonal variation of immune responses. J Infect Dis. 2011; 203(1):122–130
   PubMedGoogle Scholar
• . Chen Y, Kong J, Sun T, . 1,25-digyroxyvitamin D3 suppresses inflammation-induced expression of plasminogen activator inhibitor-1 by blocking nuclear factor-kB activation. Arch Biochem Biophys. 2011; 507(2):241–247
   PubMed Web of Science ®Google Scholar
• . Anderson JL, May HT, Horne DB, . Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010; 106(7):963–968
   PubMed Web of Science ®Google Scholar
• . Hall LM, Kimlin MG, Aronov PA, . Vitamin D intake needed to maintain target serum 25-hydroxyvitamin D concentrations in participants with low sun exposure and dark skin pigmentation is substantially higher than current recommendations. J Nutr. 2010; 140(3):542–550
   PubMed Web of Science ®Google Scholar
• . Elliott ME, Binkley NC, Carnes M, . Fracture risks for women in long-term care: High prevalence of calcaneal osteoporosis and hypovitaminosis D. Pharmacotherapy. 2003; 23(6):702–710
   PubMedGoogle Scholar
• . Thomas MK, Lloyd-Jones DM, Thadhani RI, . Hypovitaminosis D in medical inpatients. N Engl J Med. 1998; 338(12):777–783
   PubMed Web of Science ®Google Scholar
• . Tangpricha V, Pearce EN, Chen TC, Holick MF. Vitamin D insufficiency among free-living healthy young adults. Am J Med. 2002; 112(8):659–662
   PubMed Web of Science ®Google Scholar
• . National Institutes of Health. Vitamin D: Are There Safety Concerns? Washington, DC: United States Department of Health and Human Services; 2012. http://www.nlm.nih.gov/medlineplus/druginfo/natural/929.html. Accessed December 17, 2012
   Google Scholar
• . Araujo CC, Leon LL. Biological activities of Carcuma longa. Mem Inst Osawaldo Cruz. 2001; 96(5):723–728
   PubMed Web of Science ®Google Scholar
• . Claeson P, Panthong A, Tuchinda P, . Three non-phenolic diarylheptanoids with anti-inflammatory activity from carcuma xanthorrhiza. Planta Med. 1993; 59(5):451–454
   PubMed Web of Science ®Google Scholar
• . Natarajan C, Bright JJ. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through janus kinasestat pathway in t lymphocytes. J Immunol. 2002; 168(12):6506–6513
   PubMed Web of Science ®Google Scholar
• . Talalay P, Talalay P. The importance of using scientific principles in the development of medicinal agents from plants. Acad Med. 2001; 76(3):238–247
   PubMedGoogle Scholar
• . Hsu HY, Wen MH. Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1 gene expression. J Biol Chem. 2002; 277(25):22131–22139
   PubMed Web of Science ®Google Scholar
• . Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Thomas P, Dannenberg AJ. Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of nf-kappa-b-dependent genes. Am J Physiol Gastrointest Liver Physiol. 2003; 284(2):G321–G327
   PubMedGoogle Scholar
• . Jachak SM. Cyclooxygenase inhibitory natural products: Current status. Curr Med Chem. 2006; 13(6):659–678
   PubMed Web of Science ®Google Scholar
• . Jiang H, Tian X, Guo Y, Duan W, Bu H, Li C. Activation of nuclear factor erythroid 2-related factor 2 cytoprotective signaling by curcumin protect primary spinal cord astrocytes against oxidative toxicity. Biol Pharmacol Bull. 2011; 34(8):1194–1197
   PubMedGoogle Scholar
• . Erlank H, Elmann A, Kohen R, Kanner J. Polyphenols activate Nrf2 in astrocytes via J(2)0(2), semiquinones, and quinones. Free Radic Biol Med. 2011; 51(12):2319–2327
   PubMedGoogle Scholar
• . Zhao SG, Li Q, Liu ZX, . Curcumin attenuates insulin resistance in hepatocytes by inducing Nrf2 nuclear translocation. Hepatogastroenterology. 2011; 58(112):2106–2111
   PubMedGoogle Scholar
• . Goepp JG. What is nuclear factor-kappa beta? Life Extension Mag. http://www.lef.org/magazine/mag2006/jul2006_report_nuclear_01.htm#AnchorFushion. Published July 2006. Accessed November 19, 2012
   Google Scholar
• . Bengmark S. Curcumin, an atoxic antioxidant and natural NFk b, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: A shield against acute and chronic disease. JPEN J Parenter Enteral Nutr. 2006; 30(1):45–51
   PubMed Web of Science ®Google Scholar
• . Plummer SM, Holloway KA, Manson MM, . Inhibition of Cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of nf-κ b activation via the nik/ikk signaling complex. Oncogene. 1999; 18(44):6013–6020
   PubMed Web of Science ®Google Scholar
• . Laird MD, Sukumari-Ramesh S, Swift AE, Meiler SE, Vender JR, Dhandapani KM. Curcumin attenuates cerebral edema following traumatic brain injury in mice: A possible role for aquaporin-4? J Neurochem. 2010; 113(3):637–648
   PubMed Web of Science ®Google Scholar
• . Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001; 21(21):8370–8377
   PubMed Web of Science ®Google Scholar
• . Dohare P, Garg P, Jain V, Nath C, Ray M. Dose dependence and therapeutic window for the neuroprotective effects of curcumin in thromboembolic model of rat. Behav Brain Res. 2008; 193(2):289–297
   PubMedGoogle Scholar
• . Zhao J, Yu S, Zheng W, Feng G, Luo G, Wang L, Zhao Y. Curcumin improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats. Neurochem Res. 2010; 35(3):374–379
   PubMed Web of Science ®Google Scholar
• . Jiang J, Wang W, Sun YJ, Hu M, Li F, Zhu DY. Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood—brain barrier damage. Eur J Pharmacol. 2007; 561(1–3):54–62
   PubMed Web of Science ®Google Scholar
• . Badria FA, El-Farahaty T, Shabana AA, Hawas SA, El-Batory MF. Boswellia-curcumin preparation for treating knee osteoarthritis: A clinical evaluation. Alt Complement Ther. 2002; 8(6):341–348
   Google Scholar
• . Berman B. Turmeric. University of Maryland Medical Center. http://www.umm.edu/atlmed/ConsHerbs/Turmericch.html. Published 2004. Accessed September 22, 2011
   Google Scholar
• . Baur JA, Sinclain DA. Therapeutic potential of resveratrol: The in vivo evidence. Nat Rev Drug Discov. 2006; 5(6):493–506
   PubMed Web of Science ®Google Scholar
• . Baur JA, Pearson KJ, Price NL, . Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006; 444(7117):337–342
   PubMed Web of Science ®Google Scholar
• . Bradamante S, Barenghi L, Villa A. Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev. 2004; 22(3):169–188
   PubMed Web of Science ®Google Scholar
• . Karuppagounder SS, Pinto JT, Xu H, Chen HL, Beal MF, Gibson GE. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease. Neurochem Int. 2009; 54(2):111–118
   PubMed Web of Science ®Google Scholar
• . Richard T, Pawlus AD, Iglesias ML, . Neuroprotective properties of resveratrol and derivatives. Ann N Y Acad Sci. 2011; 1215:103–108
   PubMed Web of Science ®Google Scholar
• . Gao D, Zhang X, Jiang X, . Resveratrol reduces the elevated level of MMP-9 induced by cerebral ischemia-reperfusion in mice. Life Sci. 2006; 78(22):2564–2570
   PubMed Web of Science ®Google Scholar
• . Sinha K, Chaudhary G, Gupta YK. Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats. Life Sci. 2002; 71(6):655–665
   PubMed Web of Science ®Google Scholar
• . Smoliga JM, Baur JA, Hausenblas HA. Resveratrol and health—a comprehensive review of human clinical trials. Mol Nutr Food Res. 2011; 55(8):1129–1141
   PubMed Web of Science ®Google Scholar
• . Elmali N, Baysal O, Harma A, Esenkaya I, Mizrak B. Effects of resveratrol in inflammatory arthritis. Inflammation. 2007; 30(1–2):1–6
   PubMed Web of Science ®Google Scholar
• . Kaplan S, Bisleri G, Morgan JA, Cheema FH, Oz MC. Resveratrol, a natural red wine polyphenol, reduces ischemia-reperfusion-induced spinal cord injury. Ann Thorac Surg. 2005; 80(6):2242–2249
   PubMedGoogle Scholar
• . Sönmez U, Sönmez A, Erbil G, Tekmen I, Baykara B. Neuroprotective effects of resveratrol against traumatic brain injury in immature rats. Neurosci Lett. 2007; 420(2):133–137
   PubMedGoogle Scholar
• . Singleton RH, Yan HQ, Fellows-Mayle W, Dixon CE. Resveratrol attenuates behavioral impairments and reduces cortical and hippocampal loss in a rat controlled cortical impact model of traumatic brain injury. J Neurotrauma. 2010; 27(6):1091–1099
   PubMed Web of Science ®Google Scholar
• . Li C, Yan Z, Yang J, . Neuroprotective effects of resveratrol on ischemic injury mediated by modulating the release of neurotransmitter and neuromodulator in rats. Neurochem Int. 2010; 56(3):495–500
   PubMed Web of Science ®Google Scholar
• . Karlsen A, Paur I, Bohn SK, . Bilberry juice modulates plasma concentration of NF-kappaB related inflammatory markers in subjects at increased risk of CVD. Eur J Nutr. 2010; 49(6):345–355
   PubMed Web of Science ®Google Scholar
• . Yang YB, Piao YJ. Effects of resveratrol on secondary damages after acute spinal cord injury in rats. Acta Pharmacol Sin. 2003; 24(7):703–710
   PubMedGoogle Scholar
• . Ates O, Cayli S, Altinoz E, . Neuroprotection by resveratrol against traumatic brain injury in rats. Mol Cell Biochem. 2007; 294(1–2):137–144
   PubMedGoogle Scholar
• . Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides. J Biol Chem. 2005; 280(45):37377–37382
   PubMed Web of Science ®Google Scholar
• . Lindsay J, Laurin D, Verreault R, . Risk factors for Alzheimer's disease: A progressive analysis from the Canadian Study of Health and Aging. Am J Epidemiol. 2002; 156(5):445–453
   PubMed Web of Science ®Google Scholar
• . Fox C, Ramsoomair D, Carter C. Magnesium: Its proven and potential clinical significance. South Med J. 2001; 94(12):1195–1201
   PubMed Web of Science ®Google Scholar
• . Johnson JW, Ascher P. Voltage-dependent block by intracellular Mg2+ of N-methyl-D-aspartate-activated channels. Biophys J. 1990; 57(5):1085–1090
   PubMedGoogle Scholar
• . Lin JY, Chung SY, Lin MC, Cheng FC. Effects of magnesium sulfate on energy metabolites and glutamate in the cortex during focal cerebral ischemia and reperfusion in the gerbil monitored by a dual-probe microdialysis technique. Life Sci. 2002; 71(7):803–811
   PubMedGoogle Scholar
• . Katayama Y, Maeda T, Koshinaga M, Kawamata T, Tsubokowa T. Role of excitatory amino-acid mediated ionic fluxes in traumatic brain injury. Brain Pathol. 1995; 5(4):427–435
   PubMedGoogle Scholar
• . Mcintosh TK, Saatman KE, Raghupathi R. Calcium and the pathogenesis of traumatic cns injury: Cellular and molecular mechanisms. Neuroscientist. 1997; 3(3):169–175
   Google Scholar
• . Garfinkle L, Garfinkel D. Magnesium regulation of the glycolitic pathway and the enzymes involved. Magnesium. 1985; 4:60–72
   PubMedGoogle Scholar
• . Altura BM, Altura BT. Magnesium ions and contraction of vascular smooth muscles: Relationship to some vascular diseases. Fed Proc. 1981; 40(12):2672–2679
   PubMedGoogle Scholar
• . Health DL, Vink R. Traumatic brain axonal injury produces sustained decline in intracellular free magnesium concentration. Brain Res. 1996; 738(1):150–153
   PubMedGoogle Scholar
• . han den Heuvel C, Vink R. Role of magnesium in traumatic brain injury. Clin Calcium. 2004; 14(8):9–14
   Google Scholar
• . Nuytten D, Van Hees J, Meulemans A, Carton H. Magnesium deficiency as a cause of acute intractable seizures. J Neurol. 1991; 238(5):262–264
   PubMedGoogle Scholar
• . Cundy T, Dissanayake A. Severe hypomagnesaemia in long-term users of proton-pump inhibitors. Clin Endocrinol (Oxf). 2008; 69(2):338–341
   PubMedGoogle Scholar
• . Lampl Y, Geva D, Gilad R, Eshel Y, Ronen L, Sarova-Pinhas I. Cerebrospinal fluid magnesium level as a prognostic factor in ischaemic stroke. J Neurol. 1998; 245(9):584–588
   PubMedGoogle Scholar
• . McIntosh TK, Faden AI, Yamakami I, Vink R. Magnesium deficiency exacerbates and pretreatment improves outcome following traumatic brain injury in rats: 31P magnetic resonance spectroscopy and behavioural studies. J Neurotrauma. 1988; 5(1):17–30
   PubMedGoogle Scholar
• . Vink R, McIntosh TK, Demediuk P, Weiner MW, Faden AI. Decline in intracellular free Mg2+ is associated with irreversible tissue injury after brain trauma. J Biol Chem. 1988; 263(2):757–761
   PubMedGoogle Scholar
• . Reeves SA, Gibbs RS, Clark SL. Magnesium for fetal neuroprotection. Am J Obstet Gynecol. 2011; 204(3):202e.1–202e.4
   Google Scholar
• . Saver J, Kidwell C, Leary M. The field administration of stroke therapy-magnesium (FASTMAG) pilot trial. Abstract presented at: 26th International Stroke Conference; February 2001; Fort Lauderdale, FL
   Google Scholar
• . Ghabriel MN, Thomas A, Vink R. Magnesium restores altered aquaporin-4 immunoreactivity following traumatic brain injury to a pre-injury state. Acta Neurochirurgica Supplement. 2006; 96(10)402–406
   PubMedGoogle Scholar
• . Okiyama K, Smith DH, Gennarelli TA, Simon RP, Leach M, McIntosh TK. The sodium channel blocker and glutamate release inhibitor BW1003C87 and magnesium attenuate regional cerebral edema following experimental brain injury in the rat. J Neurochem. 1995; 64(2):802–809
   PubMedGoogle Scholar
• . Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. Washington, DC: National Academy Press; 1997
   Google Scholar
• . Zierath J, Kaiserauer S, Snyder AC. Dietary patterns of amenorrheic and regularly menstruating runners. Med Sci Sports Exerc. 1986; 18( suppl):S55–S56
   Google Scholar
• . Lukaski HC. Magnesium, zinc, and chromium nutriture and physical activity. Am J Clin Nutr. 2000; 72( suppl):585S–593S
   PubMed Web of Science ®Google Scholar
• . Lukaski HC. Micronutrients (magnesium, zinc, and copper): Are mineral supplements needed for athletes? Intl J Sport Nutr. 1995; 5( suppl):S74–S83
   PubMedGoogle Scholar
• . Sen AP, Gulati A. The use of magnesium in traumatic brain injury. Neurotherapeutics. 2010; 7(1):91–99
   PubMed Web of Science ®Google Scholar
• . Chen PC, Wheeler DS, Malhorta V, Odoms K, Denenberg AG, Wong HR. A green tea-derived polyphenol, epigallocatechin-3-gallate, inhibts I[kappa]B kinase activation and IL-8 gene expression. Inflammation. 2002; 26(5):233–241
   PubMedGoogle Scholar
• . Ghosh S, May MJ, Kopp EB. NF-kB and Rel proteins: Evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998; 16:225–260
   PubMed Web of Science ®Google Scholar
• . Kanakaraj P, Schafer PH, Cavender DE, . Interleukin (IL)-1 receptor-associated kinase (IRAK) requirement for optimal induction of multiple IL-1 signaling pathways and IL-6 production. J Exp Med. 1998; 187(12):2073–2079
   PubMedGoogle Scholar
• . Thomas JA, Allen JL, Tsen M, . Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase. J Immunol. 1999; 163(2):978–984
   PubMedGoogle Scholar
• . Swantek JL, Tsen MF, Cobb MH, Thomas JA. IL-1 receptor associated kinase modulates host responsiveness to endotoxin. J Immunol. 2000; 164(8):4301–4306
   PubMed Web of Science ®Google Scholar
• . Wheeler DS, Catravas JD, Odoms K, Denenberg A, Malhotra V, Wong HR. Epigallocatechin-3-gallate, a green tea-derived polyphenol, inhibts IL-1beta-dependent proinflammatory signal transduction in cultured respiratory epithelial cells. J Nutr. 2004; 134(5):1039–1044
   PubMedGoogle Scholar
• . Cao H, Kelly MA, Kari F, . Green tea increases anti-inflammatory tristetraprolin and decreases pro-inflammatory tumor necrosis factor mRNA levels in rats. J Inflamm (Lond). 2007; 4:1
   PubMedGoogle Scholar
• . Aktas O, Prozorovski T, Smorodchenko A, . Green tea epigallocatechin-3-gallate mediates t cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune encephalomyelitis. J Immunol. 2004; 173(9):5794–5800
   PubMed Web of Science ®Google Scholar
• . Seeram NP, Henning SM, Niu Y, Lee R, Scheuller HS, Heber D. Catechin and caffeine content of green tea dietary supplements and correlation with antioxidant capacity. J Agric Food Chem. 2006; 54(5):1599–1603
   PubMed Web of Science ®Google Scholar