References

All of our product research is backed by science.
The references are summed up here. 


Neuroinflammation general

1. da Fonseca, A. C. C., Matias, D., Garcia, C., Amaral, R., Geraldo, L. H., Freitas, C., & Lima, F. R. S. (2014). The impact of microglial activation on blood-brain barrier in brain diseases. Frontiers in cellular neuroscience8, 362.https://www.frontiersin.org/articles/10.3389/fncel.2014.00362
2. Madore, C., Leyrolle, Q., Lacabanne, C., Benmamar-Badel, A., Joffre, C., Nadjar, A., & Layé, S. (2016). Neuroinflammation in autism: plausible role of maternal inflammation, dietary omega 3, and microbiota. Neural plasticity2016.https://www.hindawi.com/journals/np/2016/3597209/abs/
3. Herman, F. J., & Pasinetti, G. M. (2018). Principles of inflammasome priming and inhibition: implications for psychiatric disorders. Brain, behavior, and immunity73, 66-84.https://www.sciencedirect.com/science/article/pii/S0889159118302265
4. Block, M. L., Zecca, L., & Hong, J. S. (2007). Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nature Reviews Neuroscience8(1), 57-69. https://www.nature.com/articles/nrn2038?r=1&l=ri&fst=0
5. Hickman, S., Izzy, S., Sen, P., Morsett, L., & El Khoury, J. (2018). Microglia in neurodegeneration. Nature neuroscience21(10), 1359-1369.https://www.nature.com/articles/s41593-018-0242-x
6. Norden, D. M., & Godbout, J. P. (2013). Microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathology and applied neurobiology39(1), 19-34.https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2990.2012.01306.x
7. Tay, T. L., Savage, J. C., Hui, C. W., Bisht, K., & Tremblay, M. È. (2017). Microglia across the lifespan: from origin to function in brain development, plasticity and cognition. The Journal of physiology595(6), 1929-1945.https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP272134@10.1002/(ISSN)1469-7793.Experimental-Biology-2018
8. Wang, Y., & Kasper, L. H. (2014). The role of microbiome in central nervous system disorders. Brain, behavior, and immunity38, 1-12. https://www.sciencedirect.com/science/article/pii/S0889159113006004
9. Estes, M. L., & McAllister, A. K. (2016). Maternal immune activation: Implications for neuropsychiatric disorders. Science353(6301), 772-777. https://science.sciencemag.org/content/353/6301/772.abstract
10. Liang, Z., Zhao, Y., Ruan, L., Zhu, L., Jin, K., Zhuge, Q., ... & Zhao, Y. (2017). Impact of aging immune system on neurodegeneration and potential immunotherapies. Progress in Neurobiology157, 2-28. https://www.sciencedirect.com/science/article/pii/S0301008215300484
11. Lynch, M. A., & Mills, K. H. (2012). Immunology meets neuroscience–opportunities for immune intervention in neurodegenerative diseases. Brain, behavior, and immunity26(1), 1-10.https://www.sciencedirect.com/science/article/pii/S0889159111001929
12. Ransohoff, R. M. (2016). How neuroinflammation contributes to neurodegeneration. Science353(6301), 777-783.https://science.sciencemag.org/content/353/6301/777.abstract
13. Allen, N. J., & Barres, B. A. (2009). Glia—more than just brain glue. Nature457(7230), 675-677.https://www.nature.com/articles/457675a
14. Sandhu, K. V., Sherwin, E., Schellekens, H., Stanton, C., Dinan, T. G., & Cryan, J. F. (2017). Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry. Translational Research179, 223-244. https://www.sciencedirect.com/science/article/pii/S193152441630264X
15. Yirmiya, R., Rimmerman, N., & Reshef, R. (2015). Depression as a microglial disease. Trends in neurosciences38(10), 637-658.https://www.sciencedirect.com/science/article/pii/S0166223615001769
16. Perrine, K., Helcer, J., Tsiouris, A. J., Pisapia, D. J., & Stieg, P. (2017). The current status of research on chronic traumatic encephalopathy. World Neurosurgery102, 533-544.https://www.sciencedirect.com/science/article/pii/S1878875017302577
17. Morris, G., Berk, M., Walder, K., & Maes, M. (2015). Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses. BMC medicine13(1), 28.https://link.springer.com/article/10.1186/s12916-014-0259-2
18. El-Ansary, A., & Al Dera, H. (2016). Biomarkers directed strategies to treat autism. Role of Biomarkers in Medicine. In Tech Publisher, 205-28.https://books.google.com/books?hl=en&lr=&id=jG-QDwAAQBAJ&oi=fnd&pg=PA205&dq=biomarkers+directed+strategies+to+treat+autism&ots=-y9W8RFkRF&sig=hD6pupXDdzAPayqn0hR6CAHEwpQ
19. Calabrese, V., Santoro, A., Monti, D., Crupi, R., Di Paola, R., Latteri, S., ... & Franceschi, C. (2018). Aging and Parkinson's Disease: Inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis. Free Radical Biology and Medicine115, 80-91.https://www.sciencedirect.com/science/article/pii/S0891584917311620

Clinical severity of neuroinflammation

1. Popovich, P. G., & Popovich, P. G. (2014). Neuroimmunology of traumatic spinal cord injury: a brief history and overview. Experimental neurology, (258), 1-4.https://www.infona.pl/resource/bwmeta1.element.elsevier-97188ead-3970-3725-b69b-46a4d9b7fb5c
2. Schwab, J. M., Zhang, Y., Kopp, M. A., Brommer, B., & Popovich, P. G. (2014). The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury. Experimental neurology258, 121-129. https://www.sciencedirect.com/science/article/pii/S0014488614001253
3. Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J. (2017). Neuroimmunology of traumatic brain injury: time for a paradigm shift. Neuron95(6), 1246-1265.https://www.sciencedirect.com/science/article/pii/S0896627317306128
4. Guerrero-García, J. D. J., Carrera-Quintanar, L., López-Roa, R. I., Márquez-Aguirre, A. L., Rojas-Mayorquín, A. E., & Ortuño-Sahagún, D. (2016). Multiple sclerosis and obesity: possible roles of adipokines. Mediators of inflammation2016. https://www.hindawi.com/journals/mi/2016/4036232/abs/
5. Li, J. W., Zong, Y., Cao, X. P., Tan, L., & Tan, L. (2018). Microglial priming in Alzheimer’s disease. Annals of translational medicine6(10).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994530/
6. Norden, D. M., Muccigrosso, M. M., & Godbout, J. P. (2015). Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease. Neuropharmacology96, 29-41.https://www.sciencedirect.com/science/article/pii/S0028390814004031
7. Hoeijmakers, L., Heinen, Y., Van Dam, A. M., Lucassen, P. J., & Korosi, A. (2016). Microglial priming and Alzheimer’s disease: a possible role for (early) immune challenges and epigenetics?. Frontiers in human neuroscience10, 398. https://www.frontiersin.org/articles/10.3389/fnhum.2016.00398/full
8. Niraula, A., Sheridan, J. F., & Godbout, J. P. (2017). Microglia priming with aging and stress. Neuropsychopharmacology42(1), 318-333.https://www.nature.com/articles/npp2016185/
9. Block, M. L., & Hong, J. S. (2005). Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Progress in neurobiology76(2), 77-98.https://www.sciencedirect.com/science/article/pii/S0301008205000675
10. Loane, D. J., & Kumar, A. (2016). Microglia in the TBI brain: the good, the bad, and the dysregulated. Experimental neurology275, 316-327.https://www.sciencedirect.com/science/article/pii/S0014488615300790
11. Jin, X., & Yamashita, T. (2016). Microglia in central nervous system repair after injury. The Journal of Biochemistry159(5), 491-496.https://academic.oup.com/jb/article-abstract/159/5/491/1750705
12. Henriques, J. F., Portugal, C. C., Canedo, T., Relvas, J. B., Summavielle, T., & Socodato, R. (2018). Microglia and alcohol meet at the crossroads: Microglia as critical modulators of alcohol neurotoxicity. Toxicology letters283, 21-31.https://www.sciencedirect.com/science/article/pii/S0378427417314509
13. Perry, V. H., & Teeling, J. (2013, September). Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. In Seminars in immunopathology (Vol. 35, No. 5, pp. 601-612). Springer Berlin Heidelberg.https://link.springer.com/article/10.1007/s00281-013-0382-8
14. Perry, V. H., & Teeling, J. (2013, September). Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. In Seminars in immunopathology (Vol. 35, No. 5, pp. 601-612). Springer Berlin Heidelberg. https://link.springer.com/article/10.1007/s00281-013-0382-8
15. Kiernan, E. A., Smith, S. M., Mitchell, G. S., & Watters, J. J. (2016). Mechanisms of microglial activation in models of inflammation and hypoxia: Implications for chronic intermittent hypoxia. The Journal of physiology594(6), 1563-1577.https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP271502@10.1111/(ISSN)1469-7793.SLEEPVI
16. Kiernan, E. A., Smith, S. M., Mitchell, G. S., & Watters, J. J. (2016). Mechanisms of microglial activation in models of inflammation and hypoxia: Implications for chronic intermittent hypoxia. The Journal of physiology594(6), 1563-1577.https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP271502@10.1111/(ISSN)1469-7793.SLEEPVI
17. Fumagalli, S., Perego, C., Pischiutta, F., Zanier, E. R., & De Simoni, M. G. (2015). The ischemic environment drives microglia and macrophage function. Frontiers in neurology6, 81.https://www.frontiersin.org/articles/10.3389/fneur.2015.00081/full
18. Sapin, E., Peyron, C., Roche, F., Gay, N., Carcenac, C., Savasta, M., ... & Dematteis, M. (2015). Chronic intermittent hypoxia induces chronic low-grade neuroinflammation in the dorsal hippocampus of mice. Sleep38(10), 1537-1546. https://academic.oup.com/sleep/article-abstract/38/10/1537/2468595
19. Collins-Praino, L. E., Arulsamy, A., Katharesan, V., & Corrigan, F. (2018). The effect of an acute systemic inflammatory insult on the chronic effects of a single mild traumatic brain injury. Behavioural brain research336, 22-31.https://www.sciencedirect.com/science/article/pii/S0166432817312846
20. Russo, M. V., & McGavern, D. B. (2016). Inflammatory neuroprotection following traumatic brain injury. Science353(6301), 783-785.https://science.sciencemag.org/content/353/6301/783.abstract
21. Thiel, A., & Heiss, W. D. (2011). Topical Review: Imaging.https://pdfs.semanticscholar.org/de47/136aa62cd53db19cd3bfb84c0ace8d58bb3d.pdf
22. Magaki, S. D., Williams, C. K., & Vinters, H. V. (2018). Glial function (and dysfunction) in the normal & ischemic brain. Neuropharmacology134, 218-225.https://www.sciencedirect.com/science/article/pii/S002839081730518X
23. Drew, P. D., & Kane, C. J. (2014). Fetal alcohol spectrum disorders and neuroimmune changes. In International review of neurobiology (Vol. 118, pp. 41-80). Academic Press. https://www.sciencedirect.com/science/article/pii/B9780128012840000038
24. Hay, J., Johnson, V. E., Smith, D. H., & Stewart, W. (2016). Chronic traumatic encephalopathy: the neuropathological legacy of traumatic brain injury. Annual Review of Pathology: Mechanisms of Disease11, 21-45.https://www.annualreviews.org/doi/abs/10.1146/annurev-pathol-012615-044116
25. Karve, I. P., Taylor, J. M., & Crack, P. J. (2016). The contribution of astrocytes and microglia to traumatic brain injury. British journal of pharmacology173(4), 692-702.https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.13125
26. Vile, A. R., & Atkinson, L. (2017). Chronic Traumatic Encephalopathy: The cellular sequela to repetitive brain injury. Journal of Clinical Neuroscience41, 24-29. https://www.sciencedirect.com/science/article/pii/S0967586817300668
27. Ma, Y., Wang, J., Wang, Y., & Yang, G. Y. (2017). The biphasic function of microglia in ischemic stroke. Progress in neurobiology157, 247-272.https://www.sciencedirect.com/science/article/pii/S0301008215300708
28. Maccioni, R. B., González, A., Andrade, V., Cortés, N., Tapia, J. P., & Guzmán-Martínez, L. (2018). Alzheimer s disease in the perspective of neuroimmunology. The open neurology journal12, 50.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040210/
29. Doty, K. R., Guillot-Sestier, M. V., & Town, T. (2015). The role of the immune system in neurodegenerative disorders: adaptive or maladaptive?. Brain research1617, 155-173.https://www.sciencedirect.com/science/article/pii/S0006899314011950
30. Makinde, H. M., Just, T. B., Cuda, C. M., Perlman, H., & Schwulst, S. J. (2017). The role of microglia in the etiology and evolution of chronic traumatic encephalopathy. Shock (Augusta, Ga.)48(3), 276. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5555778/
31. McKee, A. C., Stein, T. D., Kiernan, P. T., & Alvarez, V. E. (2015). The neuropathology of chronic traumatic encephalopathy. Brain pathology25(3), 350-364.https://onlinelibrary.wiley.com/doi/abs/10.1111/bpa.12248
32. Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J. (2017). Neuroimmunology of traumatic brain injury: time for a paradigm shift. Neuron95(6), 1246-1265. https://www.sciencedirect.com/science/article/pii/S0896627317306128
33. Muccigrosso, M. M., Ford, J., Benner, B., Moussa, D., Burnsides, C., Fenn, A. M., ... & Godbout, J. P. (2016). Cognitive deficits develop 1 month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge. Brain, behavior, and immunity54, 95-109.https://www.sciencedirect.com/science/article/pii/S0889159116300083
34. Perry, V. H. (2010). Contribution of systemic inflammation to chronic neurodegeneration. Acta neuropathologica120(3), 277-286. https://link.springer.com/article/10.1007/s00401-010-0722-x
35. Calcia, M. A., Bonsall, D. R., Bloomfield, P. S., Selvaraj, S., Barichello, T., & Howes, O. D. (2016). Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology233(9), 1637-1650.https://link.springer.com/content/pdf/10.1007/s00213-016-4218-9.pdf
36. Lim, J. S., & Kwon, H. M. (2010). Risk of “silent stroke” in patients older than 60 years: risk assessment and clinical perspectives. Clinical interventions in aging5, 239https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938031/
37. Asken, B. M., Sullan, M. J., DeKosky, S. T., Jaffee, M. S., & Bauer, R. M. (2017). Research gaps and controversies in chronic traumatic encephalopathy: a review. JAMA neurology74(10), 1255-1262.https://jamanetwork.com/journals/jamaneurology/article-abstract/2654232
38. Napoli, I., & Neumann, H. (2010). Protective effects of microglia in multiple sclerosis. Experimental neurology225(1), 24-28. https://www.sciencedirect.com/science/article/pii/S0014488609001599
39. Witcher, K. G., Eiferman, D. S., & Godbout, J. P. (2015). Priming the inflammatory pump of the CNS after traumatic brain injury. Trends in neurosciences38(10), 609-620. https://www.sciencedirect.com/science/article/pii/S0166223615001770
40. Kerner, N. A., & Roose, S. P. (2016). Obstructive sleep apnea is linked to depression and cognitive impairment: evidence and potential mechanisms. The American Journal of Geriatric Psychiatry24(6), 496-508..https://www.sciencedirect.com/science/article/pii/S1064748116001378

Lifestyle and dietary approach to Neuroinflammation

1. Rea, K., Dinan, T. G., & Cryan, J. F. (2016). The microbiome: a key regulator of stress and neuroinflammation. Neurobiology of stress4, 23-33.https://www.sciencedirect.com/science/article/pii/S2352289515300370
2. Kim, Y. K., & Won, E. (2017). The influence of stress on neuroinflammation and alterations in brain structure and function in major depressive disorder. Behavioural brain research329, 6-11.https://www.sciencedirect.com/science/article/pii/S0166432817303303
3. Calcia, M. A., Bonsall, D. R., Bloomfield, P. S., Selvaraj, S., Barichello, T., & Howes, O. D. (2016). Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology233(9), 1637-1650.https://link.springer.com/content/pdf/10.1007/s00213-016-4218-9.pdf
4. Bellesi, M., de Vivo, L., Chini, M., Gilli, F., Tononi, G., & Cirelli, C. (2017). Sleep loss promotes astrocytic phagocytosis and microglial activation in mouse cerebral cortex. Journal of Neuroscience37(21), 5263-5273.https://www.jneurosci.org/content/37/21/5263?utm_source=TrendMD&utm_medium=cpc&utm_campaign=JNeurosci_TrendMD_1  
5. Bernier, M., Wahl, D., Ali, A., Allard, J., Faulkner, S., Wnorowski, A., ... & Tarantini, S. (2016). Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet. Aging (Albany NY)8(5), 899.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931843/
6. Zhu, B., Dong, Y., Xu, Z., Gompf, H. S., Ward, S. A., Xue, Z., ... & Xie, Z. (2012). Sleep disturbance induces neuroinflammation and impairment of learning and memory. Neurobiology of disease48(3), 348-355.https://www.sciencedirect.com/science/article/pii/S0969996112002379
7. Piirainen, S., Youssef, A., Song, C., Kalueff, A. V., Landreth, G. E., Malm, T., & Tian, L. (2017). Psychosocial stress on neuroinflammation and cognitive dysfunctions in Alzheimer's disease: the emerging role for microglia?. Neuroscience & Biobehavioral Reviews77, 148-164.https://www.sciencedirect.com/science/article/pii/S0149763416304857
8. Spielman, L. J., Little, J. P., & Klegeris, A. (2016). Physical activity and exercise attenuate neuroinflammation in neurological diseases. Brain Research Bulletin125, 19-29.https://www.sciencedirect.com/science/article/pii/S0361923016300557
9. Guillemot-Legris, O., & Muccioli, G. G. (2017). Obesity-induced neuroinflammation: beyond the hypothalamus. Trends in Neurosciences40(4), 237-253.https://www.sciencedirect.com/science/article/pii/S0166223617300255
10. Miller, A. A., & Spencer, S. J. (2014). Obesity and neuroinflammation: a pathway to cognitive impairment. Brain, behavior, and immunity42, 10-21.https://www.sciencedirect.com/science/article/pii/S0889159114000889
11. Vauzour, D., Camprubi-Robles, M., Miquel-Kergoat, S., Andres-Lacueva, C., Bánáti, D., Barberger-Gateau, P., ... & Kiliaan, A. J. (2017). Nutrition for the ageing brain: towards evidence for an optimal diet. Ageing research reviews35, 222-240.https://www.sciencedirect.com/science/article/pii/S1568163716301027
12. Vauzour, D., Camprubi-Robles, M., Miquel-Kergoat, S., Andres-Lacueva, C., Bánáti, D., Barberger-Gateau, P., ... & Kiliaan, A. J. (2017). Nutrition for the ageing brain: towards evidence for an optimal diet. Ageing research reviews35, 222-240.https://www.sciencedirect.com/science/article/pii/S1568163716301027
13. Kang, E. B., Koo, J. H., Jang, Y. C., Yang, C. H., Lee, Y., Cosio‐Lima, L. M., & Cho, J. Y. (2016). Neuroprotective Effects of Endurance Exercise Against High‐Fat Diet‐Induced Hippocampal Neuroinflammation. Journal of neuroendocrinology28(5).https://onlinelibrary.wiley.com/doi/abs/10.1111/jne.12385
14. Moreno-Navarrete, J. M., Blasco, G., Puig, J., Biarnes, C., Rivero, M., Gich, J., ... & Garcia-Castro, F. (2017). Neuroinflammation in obesity: circulating lipopolysaccharide-binding protein associates with brain structure and cognitive performance. International Journal of Obesity41(11), 1627-1635.https://www.nature.com/articles/ijo2017162
15. Buric, I., Farias, M., Jong, J., Mee, C., & Brazil, I. A. (2017). What is the molecular signature of mind–body interventions? A systematic review of gene expression changes induced by meditation and related practices. Frontiers in Immunology8, 670.https://www.frontiersin.org/articles/10.3389/fimmu.2017.00670/full?source=post_page---------------------------
16. Nadjar, A., Wigren, H. K. M., & Tremblay, M. E. (2017). Roles of microglial phagocytosis and inflammatory mediators in the pathophysiology of sleep disorders. Frontiers in cellular neuroscience11, 250.https://www.frontiersin.org/articles/10.3389/fncel.2017.00250/full
17. Kalsbeek, M. J., Mulder, L., & Yi, C. X. (2016). Microglia energy metabolism in metabolic disorder. Molecular and cellular endocrinology438, 27-35.https://www.sciencedirect.com/science/article/pii/S0303720716304026
18. Valdearcos, M., Robblee, M. M., Benjamin, D. I., Nomura, D. K., Xu, A. W., & Koliwad, S. K. (2014). Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell reports9(6), 2124-2138.https://www.sciencedirect.com/science/article/pii/S2211124714009723
19. Tse, J. K. (2017). Gut microbiota, nitric oxide, and microglia as prerequisites for neurodegenerative disorders. ACS chemical neuroscience8(7), 1438-1447. https://pubs.acs.org/doi/abs/10.1021/acschemneuro.7b00176
20. Peng, H., Nickell, C. R. G., Chen, K. Y., McClain, J. A., & Nixon, K. (2017). Increased expression of M1 and M2 phenotypic markers in isolated microglia after four-day binge alcohol exposure in male rats. Alcohol62, 29-40. https://www.sciencedirect.com/science/article/pii/S0741832916306322
21. Manchanda, S., Singh, H., Kaur, T., & Kaur, G. (2018). Low-grade neuroinflammation due to chronic sleep deprivation results in anxiety and learning and memory impairments. Molecular and cellular biochemistry449(1-2), 63-72. https://link.springer.com/article/10.1007/s11010-018-3343-7
22. Yin, Z., Raj, D. D., Schaafsma, W., van der Heijden, R. A., Kooistra, S. M., Reijne, A. C., ... & Yi, C. X. (2018). Low-fat diet with caloric restriction reduces white matter microglia activation during aging. Frontiers in molecular neuroscience11, 65.https://www.frontiersin.org/articles/10.3389/fnmol.2018.00065/full?_ga=2.22854206.449367120.1527552000-1350799375.1527552000
23. Valero, J., Paris, I., & Sierra, A. (2016). Lifestyle shapes the dialogue between environment, microglia, and adult neurogenesis. ACS chemical neuroscience7(4), 442-453.https://pubs.acs.org/doi/abs/10.1021/acschemneuro.6b00009
24. Piao, C. S., Stoica, B. A., Wu, J., Sabirzhanov, B., Zhao, Z., Cabatbat, R., ... & Faden, A. I. (2013). Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury. Neurobiology of disease54, 252-263.https://www.sciencedirect.com/science/article/pii/S0969996113000089
25. Simeone, T. A., Simeone, K. A., & Rho, J. M. (2017). Ketone bodies as anti-seizure agents. Neurochemical research42(7), 2011-2018.https://link.springer.com/article/10.1007/s11064-017-2253-5
26. Jeong, E. A., Jeon, B. T., Shin, H. J., Kim, N., Lee, D. H., Kim, H. J., ... & Roh, G. S. (2011). Ketogenic diet-induced peroxisome proliferator-activated receptor-γ activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures. Experimental neurology232(2), 195-202. https://www.sciencedirect.com/science/article/pii/S0014488611003086
27. Cullingford, T. E. (2004). The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders. Prostaglandins, leukotrienes and essential fatty acids70(3), 253-264. https://www.sciencedirect.com/science/article/pii/S0952327803002163
28. Jeong, E. A., Jeon, B. T., Shin, H. J., Kim, N., Lee, D. H., Kim, H. J., ... & Roh, G. S. (2011). Ketogenic diet-induced peroxisome proliferator-activated receptor-γ activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures. Experimental neurology232(2), 195-202.https://www.sciencedirect.com/science/article/pii/S0014488611003086
29. Vasconcelos, A. R., Yshii, L. M., Viel, T. A., Buck, H. S., Mattson, M. P., Scavone, C., & Kawamoto, E. M. (2014). Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment. Journal of neuroinflammation11(1), 1-14.https://link.springer.com/article/10.1186/1742-2094-11-85?fbclid=IwAR3dip0J8Lc1jIQSvqAqg1z9oo9XUfBauoRAK0zUvEujKZgKonVgVEZ27F8&error=cookies_not_supported&code=f3ff3856-a534-4d20-b664-0b12d80f19c1
30. André, C., Guzman-Quevedo, O., Rey, C., Rémus-Borel, J., Clark, S., Castellanos-Jankiewicz, A., ... & Laye, S. (2017). Inhibiting microglia expansion prevents diet-induced hypothalamic and peripheral inflammation. Diabetes66(4), 908-919.https://diabetes.diabetesjournals.org/content/66/4/908.abstract
31. Van Dyken, P., & Lacoste, B. (2018). Impact of metabolic syndrome on neuroinflammation and the blood–brain barrier. Frontiers in neuroscience12, 930.https://www.frontiersin.org/articles/10.3389/fnins.2018.00930/full
32. Brockmeyer, S., & d’Angiulli, A. (2016). How air pollution alters brain development: the role of neuroinflammation. Translational neuroscience7(1), 24-30.https://www.degruyter.com/view/journals/tnsci/7/1/article-p24.xml
33. Spencer, S. J., D'Angelo, H., Soch, A., Watkins, L. R., Maier, S. F., & Barrientos, R. M. (2017). High-fat diet and aging interact to produce neuroinflammation and impair hippocampal-and amygdalar-dependent memory. Neurobiology of aging58, 88-101.https://www.sciencedirect.com/science/article/pii/S0197458017302105
34. Tse, J. K. (2017). Gut microbiota, nitric oxide, and microglia as prerequisites for neurodegenerative disorders. ACS chemical neuroscience8(7), 1438-1447.https://pubs.acs.org/doi/abs/10.1021/acschemneuro.7b00176
35. Olson, C. A., Vuong, H. E., Yano, J. M., Liang, Q. Y., Nusbaum, D. J., & Hsiao, E. Y. (2018). The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell173(7), 1728-1741.https://www.sciencedirect.com/science/article/pii/S0092867418305208
36. Johnson, R. W. (2015). Feeding the beast: can microglia in the senescent brain be regulated by diet?. Brain, behavior, and immunity43, 1-8.https://www.sciencedirect.com/science/article/pii/S0889159114004784
37. Catani, M. V., Gasperi, V., Bisogno, T., & Maccarrone, M. (2018). Essential dietary bioactive lipids in neuroinflammatory diseases. Antioxidants & redox signaling29(1), 37-60.
39. Yegambaram, M., Manivannan, B., G Beach, T., & U Halden, R. (2015). Role of environmental contaminants in the etiology of Alzheimer’s disease: a review. Current Alzheimer Research12(2), 116-146.https://www.ingentaconnect.com/content/ben/car/2015/00000012/00000002/art00004
40. Janakiraman, M., & Krishnamoorthy, G. (2018). Emerging role of diet and microbiota interactions in neuroinflammation. Frontiers in immunology9, 2067.https://www.frontiersin.org/articles/10.3389/fimmu.2018.02067/full
41. Bellesi, M., de Vivo, L., Tononi, G., & Cirelli, C. (2015). Effects of sleep and wake on astrocytes: clues from molecular and ultrastructural studies. BMC biology13(1), 66.https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-015-0176-7?optIn=false
42. Svensson, M., Lexell, J., & Deierborg, T. (2015). Effects of physical exercise on neuroinflammation, neuroplasticity, neurodegeneration, and behavior: what we can learn from animal models in clinical settings. Neurorehabilitation and neural repair29(6), 577-589.https://journals.sagepub.com/doi/abs/10.1177/1545968314562108
43. Tran, D. Q., Erika, K. T., Kim, M. H., & Belsham, D. D. (2016). Diet-induced cellular neuroinflammation in the hypothalamus: Mechanistic insights from investigation of neurons and microglia. Molecular and cellular endocrinology438, 18-26.https://www.sciencedirect.com/science/article/pii/S0303720716301642
44. Gao, Y., Bielohuby, M., Fleming, T., Grabner, G. F., Foppen, E., Bernhard, W., ... & García-Cáceres, C. (2017). Dietary sugars, not lipids, drive hypothalamic inflammation. Molecular metabolism6(8), 897-908.https://www.sciencedirect.com/science/article/pii/S2212877817302399
45. Hadem, I. K. H., Majaw, T., Kharbuli, B., & Sharma, R. (2019). Beneficial effects of dietary restriction in aging brain. Journal of Chemical Neuroanatomy95, 123-133.https://www.sciencedirect.com/science/article/pii/S0891061817300820
46. Hao, S., Dey, A., Yu, X., & Stranahan, A. M. (2016). Dietary obesity reversibly induces synaptic stripping by microglia and impairs hippocampal plasticity. Brain, behavior, and immunity51, 230-239. https://www.sciencedirect.com/science/article/pii/S0889159115300076
47. Riccio, P., & Rossano, R. (2018). Diet, gut microbiota, and vitamins D+ A in multiple sclerosis. Neurotherapeutics15(1), 75-91.https://link.springer.com/article/10.1007/s13311-017-0581-4  
48. White, K. A., Hutton, S. R., Weimer, J. M., & Sheridan, P. A. (2016). Diet-induced obesity prolongs neuroinflammation and recruits CCR2+ monocytes to the brain following herpes simplex virus (HSV)-1 latency in mice. Brain, behavior, and immunity57, 68-78.https://www.sciencedirect.com/science/article/pii/S0889159116301568
49. Tran, D. Q., Erika, K. T., Kim, M. H., & Belsham, D. D. (2016). Diet-induced cellular neuroinflammation in the hypothalamus: Mechanistic insights from investigation of neurons and microglia. Molecular and cellular endocrinology438, 18-26.https://www.sciencedirect.com/science/article/pii/S0303720716301642
50. Matt, S. M., Allen, J. M., Lawson, M. A., Mailing, L. J., Woods, J. A., & Johnson, R. W. (2018). Butyrate and dietary soluble fiber improve neuroinflammation associated with aging in mice. Frontiers in immunology9, 1832.https://www.frontiersin.org/articles/10.3389/fimmu.2018.01832/full?ref=mainstreem-dotcom
51. Ghosh, S., Castillo, E., Frias, E. S., & Swanson, R. A. (2018). Bioenergetic regulation of microglia. Glia66(6), 1200-1212. https://onlinelibrary.wiley.com/doi/abs/10.1002/glia.23271
52. García-Cáceres, C., Quarta, C., Varela, L., Gao, Y., Gruber, T., Legutko, B., ... & Le Thuc, O. (2016). Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell166(4), 867-880.https://www.sciencedirect.com/science/article/pii/S0092867416309746
53. Vojdani, A., Kharrazian, D., & Mukherjee, P. S. (2014). The prevalence of antibodies against wheat and milk proteins in blood donors and their contribution to neuroimmune reactivities. Nutrients6(1), 15-36.https://www.mdpi.com/2072-6643/6/1/15/htm

 

Microglial pathophysiology and neutraceutical strategies

1. Milbury, P. E., & Kalt, W. (2010). Xenobiotic metabolism and berry flavonoid transport across the blood− brain barrier. Journal of Agricultural and Food Chemistry58(7), 3950-3956. https://pubs.acs.org/doi/abs/10.1021/jf903529m
2. Haar, C. V., Peterson, T. C., Martens, K. M., & Hoane, M. R. (2016). Vitamins and nutrients as primary treatments in experimental brain injury: Clinical implications for nutraceutical therapies. Brain research1640, 114-129.https://www.sciencedirect.com/science/article/pii/S0006899315009695
3. Boontanrart, M., Hall, S. D., Spanier, J. A., Hayes, C. E., & Olson, J. K. (2016). Vitamin D3 alters microglia immune activation by an IL-10 dependent SOCS3 mechanism. Journal of neuroimmunology292, 126-136. https://www.sciencedirect.com/science/article/pii/S0165572816300157
4. Unno, K., Pervin, M., Nakagawa, A., Iguchi, K., Hara, A., Takagaki, A., ... & Nakamura, Y. (2017). Blood–Brain Barrier Permeability of Green Tea Catechin Metabolites and their Neuritogenic Activity in Human Neuroblastoma SH‐SY5Y Cells. Molecular nutrition & food research61(12), 1700294.https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.201700294
5. Monks, T. J., Ghersi-Egea, J. F., Philbert, M., Cooper, A. J., & Lock, E. A. (1999). Symposium overview: the role of glutathione in neuroprotection and neurotoxicity. Toxicological sciences: an official journal of the Society of Toxicology51(2), 161-177.https://academic.oup.com/toxsci/article-abstract/51/2/161/2256972
6. Rangarajan, P., Karthikeyan, A., & Dheen, S. T. (2016). Role of dietary phenols in mitigating microglia-mediated neuroinflammation. Neuromolecular medicine18(3), 453-464. https://link.springer.com/article/10.1007/s12017-016-8430-x
7. Rangarajan, P., Karthikeyan, A., & Dheen, S. T. (2016). Role of dietary phenols in mitigating microglia-mediated neuroinflammation. Neuromolecular medicine18(3), 453-464. https://link.springer.com/article/10.1007/s12017-016-8430-x
8. Rojo, A. I., McBean, G., Cindric, M., Egea, J., López, M. G., Rada, P., ... & Cuadrado, A. (2014). Redox control of microglial function: molecular mechanisms and functional significance. Antioxidants & redox signaling21(12), 1766-1801.https://www.liebertpub.com/doi/abs/10.1089/ars.2013.5745
9. Dajas, F., Abin-Carriquiry, J. A., Arredondo, F., Blasina, F., Echeverry, C., Martínez, M., ... & Vaamonde, L. (2015). Quercetin in brain diseases: Potential and limits. Neurochemistry international89, 140-148.https://www.sciencedirect.com/science/article/pii/S019701861530005X
10. Laye, S. (2010). Polyunsaturated fatty acids, neuroinflammation and well being. Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA)82(4-6), 295-303.https://www.sciencedirect.com/science/article/pii/S0952327810000505
11. Omar, S. H., Scott, C. J., Hamlin, A. S., & Obied, H. K. (2017). The protective role of plant biophenols in mechanisms of Alzheimer's disease. The Journal of nutritional biochemistry47, 1-20.https://www.sciencedirect.com/science/article/pii/S0955286316307343
12. Chen, Y., Yin, M., Cao, X., Hu, G., & Xiao, M. (2018). Pro-and anti-inflammatory effects of high cholesterol diet on aged brain. Aging and disease9(3), 374.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988593/
13. Yuan, T., Ma, H., Liu, W., Niesen, D. B., Shah, N., Crews, R., ... & Seeram, N. P. (2016). Pomegranate’s neuroprotective effects against Alzheimer’s disease are mediated by urolithins, its ellagitannin-gut microbial derived metabolites. ACS chemical neuroscience7(1), 26-33.https://pubs.acs.org/doi/abs/10.1021/acschemneuro.5b00260
14. Kujawska, M., & Jodynis-Liebert, J. (2018). Polyphenols in Parkinson’s disease: A systematic review of in vivo studies. Nutrients10(5), 642. https://www.mdpi.com/2072-6643/10/5/642
15. Almeida, S., Alves, M. G., Sousa, M., Oliveira, P. F., & Silva, B. M. (2016). Are polyphenols strong dietary agents against neurotoxicity and neurodegeneration?. Neurotoxicity research30(3), 345-366. https://link.springer.com/article/10.1007/s12640-015-9590-4
16. Figueira, I., Menezes, R., Macedo, D., Costa, I., & Nunes dos Santos, C. (2017). Polyphenols beyond barriers: a glimpse into the brain. Current neuropharmacology15(4), 562-594.https://www.ingentaconnect.com/content/ben/cn/2017/00000015/00000004/art00011
17. Seo, E. J., Fischer, N., & Efferth, T. (2018). Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease. Pharmacological research129, 262-273.https://www.sciencedirect.com/science/article/pii/S1043661817311349
18. Szwajgier, D., Borowiec, K., & Pustelniak, K. (2017). The neuroprotective effects of phenolic acids: molecular mechanism of action. Nutrients9(5), 477.https://www.mdpi.com/2072-6643/9/5/477
19. Kurtys, E., Eisel, U. L., Verkuyl, J. M., Broersen, L. M., Dierckx, R. A., & de Vries, E. F. (2016). The combination of vitamins and omega-3 fatty acids has an enhanced anti-inflammatory effect on microglia. Neurochemistry international99, 206-214. https://www.sciencedirect.com/science/article/pii/S0197018616302273
20. Laye, S., Nadjar, A., Joffre, C., & Bazinet, R. P. (2018). Anti-inflammatory effects of omega-3 fatty acids in the brain: physiological mechanisms and relevance to pharmacology. Pharmacological reviews70(1), 12-38.http://pharmrev.aspetjournals.org/content/70/1/12.abstract
21. Peña-Altamira, E., Petralla, S., Massenzio, F., Virgili, M., Bolognesi, M. L., & Monti, B. (2017). Nutritional and pharmacological strategies to regulate microglial polarization in cognitive aging and Alzheimer’s disease. Frontiers in Aging Neuroscience9, 175.https://www.frontiersin.org/articles/10.3389/fnagi.2017.00175/full
22. Lee-anne, S. C., Lithander, F. E., Gruen, R. L., & Williams, L. T. (2014). Nutrition therapy in the optimisation of health outcomes in adult patients with moderate to severe traumatic brain injury: findings from a scoping review. Injury45(12), 1834-1841.https://www.sciencedirect.com/science/article/pii/S0020138314002824
23. Habek, M., Hojsak, I., & Brinar, V. V. (2010). Nutrition in multiple sclerosis. Clinical Neurology and Neurosurgery112(7), 616-620.https://www.sciencedirect.com/science/article/pii/S0303846710001022
24. Fernández, S. S. M., & Ribeiro, S. M. L. (2018). Nutrition and Alzheimer disease. Clinics in geriatric medicine34(4), 677-697.https://www.geriatric.theclinics.com/article/S0749-0690(18)31005-X/abstract
25. Wu, Z., Yu, J., Zhu, A., & Nakanishi, H. (2016). Nutrients, microglia aging, and brain aging. Oxidative medicine and cellular longevity2016.https://www.hindawi.com/journals/omcl/2016/7498528/abs/
26. Venigalla, M., Sonego, S., Gyengesi, E., Sharman, M. J., & Münch, G. (2016). Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease. Neurochemistry International95, 63-74.https://www.sciencedirect.com/science/article/pii/S0197018615300619
27. Packer, L., Tritschler, H. J., & Wessel, K. (1997). Neuroprotection by the metabolic antioxidant α-lipoic acid. Free radical biology and medicine22(1-2), 359-378.https://www.sciencedirect.com/science/article/pii/S0891584996002699
28. Bastianetto, S., Ménard, C., & Quirion, R. (2015). Neuroprotective action of resveratrol. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease1852(6), 1195-1201.https://www.sciencedirect.com/science/article/pii/S0925443914002920
29. Essa, M. M., Vijayan, R. K., Castellano-Gonzalez, G., Memon, M. A., Braidy, N., & Guillemin, G. J. (2012). Neuroprotective effect of natural products against Alzheimer’s disease. Neurochemical research37(9), 1829-1842. https://link.springer.com/article/10.1007/s11064-012-0799-9
30. Sawikr, Y., Yarla, N. S., Peluso, I., Kamal, M. A., Aliev, G., & Bishayee, A. (2017). Neuroinflammation in Alzheimer's disease: the preventive and therapeutic potential of polyphenolic nutraceuticals. In Advances in protein chemistry and structural biology (Vol. 108, pp. 33-57). Academic Press.https://www.sciencedirect.com/science/article/pii/S1876162317300081
31. Van, A. L., Sakayori, N., Hachem, M., Belkouch, M., Picq, M., Lagarde, M., ... & Bernoud-Hubac, N. (2016). Mechanisms of DHA transport to the brain and potential therapy to neurodegenerative diseases. Biochimie130, 163-167.https://www.sciencedirect.com/science/article/pii/S0300908416301432
32. Jaeger, B. N., Parylak, S. L., & Gage, F. H. (2018). Mechanisms of dietary flavonoid action in neuronal function and neuroinflammation. Molecular Aspects of Medicine61, 50-62.https://www.sciencedirect.com/science/article/pii/S0098299717301115
33. Lingam, I., & Robertson, N. J. (2018). Magnesium as a neuroprotective agent: a review of its use in the fetus, term infant with neonatal encephalopathy, and the adult stroke patient. Developmental neuroscience40(1), 1-12.https://www.karger.com/Article/Abstract/484891
34. Lingam, I., & Robertson, N. J. (2018). Magnesium as a neuroprotective agent: a review of its use in the fetus, term infant with neonatal encephalopathy, and the adult stroke patient. Developmental neuroscience40(1), 1-12.https://www.karger.com/Article/Abstract/484891
35. Xu, J., Wang, H., Ding, K., Zhang, L., Wang, C., Li, T., ... & Lu, X. (2014). Luteolin provides neuroprotection in models of traumatic brain injury via the Nrf2–ARE pathway. Free Radical Biology and Medicine71, 186-195.https://www.sciencedirect.com/science/article/pii/S0891584914001269
36. Costa, S. L., Silva, V. D. A., dos Santos Souza, C., Santos, C. C., Paris, I., Muñoz, P., & Segura-Aguilar, J. (2016). Impact of plant-derived flavonoids on neurodegenerative diseases. Neurotoxicity research30(1), 41-52.https://link.springer.com/article/10.1007/s12640-016-9600-1
37. Frolinger, T., Sims, S., Smith, C., Wang, J., Cheng, H., Faith, J., ... & Pasinetti, G. M. (2019). The gut microbiota composition affects dietary polyphenols-mediated cognitive resilience in mice by modulating the bioavailability of phenolic acids. Scientific reports9(1), 1-10.https://www.nature.com/articles/s41598-019-39994-6
38. Youdim, K. A., Shukitt-Hale, B., & Joseph, J. A. (2004). Flavonoids and the brain: interactions at the blood–brain barrier and their physiological effects on the central nervous system. Free Radical Biology and Medicine37(11), 1683-1693.https://www.sciencedirect.com/science/article/pii/S0891584904006355
39. Joseph, K. D. (2013). Enhanced neuroprotective effect of fish oil in combination with quercetin against 3‐nitropropionic acid induced oxidative stress in rat brain. Progress in Neuro-Psychopharmacology and Biological Psychiatry40, 83-92.https://www.sciencedirect.com/science/article/pii/S0278584612002114
40. Vauzour, D. (2012). Dietary polyphenols as modulators of brain functions: biological actions and molecular mechanisms underpinning their beneficial effects. Oxidative medicine and cellular longevity2012.https://www.hindawi.com/journals/omcl/2012/914273/abs/
41. Sun, G. Y., Simonyi, A., Fritsche, K. L., Chuang, D. Y., Hannink, M., Gu, Z., ... & Beversdorf, D. Q. (2018). Docosahexaenoic acid (DHA): An essential nutrient and a nutraceutical for brain health and diseases. Prostaglandins, Leukotrienes and Essential Fatty Acids136, 3-13.https://www.sciencedirect.com/science/article/pii/S0952327816302137
42. Tegenge, M. A., Rajbhandari, L., Shrestha, S., Mithal, A., Hosmane, S., & Venkatesan, A. (2014). Curcumin protects axons from degeneration in the setting of local neuroinflammation. Experimental neurology253, 102-110.https://www.sciencedirect.com/science/article/pii/S0014488613003828
43. Lacombe, R. S., Chouinard-Watkins, R., & Bazinet, R. P. (2018). Brain docosahexaenoic acid uptake and metabolism. Molecular Aspects of Medicine64, 109-134.https://www.sciencedirect.com/science/article/pii/S0098299717301358
44. Chuang, D. Y., Simonyi, A., Cui, J., Lubahn, D. B., Gu, Z., & Sun, G. Y. (2016). Botanical polyphenols mitigate microglial activation and microglia-induced neurotoxicity: role of cytosolic phospholipase A 2. Neuromolecular medicine18(3), 415-425.https://link.springer.com/article/10.1007/s12017-016-8419-5
45. Pandareesh, M. D., Mythri, R. B., & Bharath, M. S. (2015). Bioavailability of dietary polyphenols: Factors contributing to their clinical application in CNS diseases. Neurochemistry international89, 198-208.https://www.sciencedirect.com/science/article/pii/S0197018615300036
46. Shal, B., Ding, W., Ali, H., Kim, Y. S., & Khan, S. (2018). Anti-neuroinflammatory potential of natural products in attenuation of Alzheimer's disease. Frontiers in pharmacology9, 548.https://www.frontiersin.org/articles/10.3389/fphar.2018.00548/full
47. Spagnuolo, C., Moccia, S., & Russo, G. L. (2018). Anti-inflammatory effects of flavonoids in neurodegenerative disorders. European Journal of Medicinal Chemistry153, 105-115. https://www.sciencedirect.com/science/article/pii/S0223523417306839
48. Spagnuolo, C., Moccia, S., & Russo, G. L. (2018). Anti-inflammatory effects of flavonoids in neurodegenerative disorders. European Journal of Medicinal Chemistry153, 105-115.https://www.sciencedirect.com/science/article/pii/S0223523417306839

Neuroinflammation blood brain barrier permeability and clinical applications

1. Hou, J., Baker, L. A., Zhou, L., & Klein, R. S. (2016). Viral interactions with the blood-brain barrier: old dog, new tricks. Tissue barriers4(1), e1142492.https://www.tandfonline.com/doi/abs/10.1080/21688370.2016.1142492
2. Zhang, Y. S., Li, J. D., & Yan, C. (2018). An update on vinpocetine: new discoveries and clinical implications. European journal of pharmacology819, 30-34. https://www.sciencedirect.com/science/article/pii/S0014299917307744
3. Szakall, S., Boros, I., Balkay, L., Emri, M., Fekete, I., Kerenyi, L., ... & Galuska, L. (1998). Cerebral effects of a single dose of intravenous vinpocetine in chronic stroke patients: a PET study. Journal of neuroimaging8(4), 197-204. https://onlinelibrary.wiley.com/doi/abs/10.1111/jon199884197
4. Rendeiro, C., Rhodes, J. S., & Spencer, J. P. (2015). The mechanisms of action of flavonoids in the brain: direct versus indirect effects. Neurochemistry international89, 126-139.https://www.sciencedirect.com/science/article/pii/S0197018615300309
5. Mohammed, H. O., Starkey, S. R., Stipetic, K., Divers, T. J., Summers, B. A., & de Lahunta, A. (2008). The role of dietary antioxidant insufficiency on the permeability of the blood-brain barrier. Journal of Neuropathology & Experimental Neurology67(12), 1187-1193. https://academic.oup.com/jnen/article-abstract/67/12/1187/2916972
6. Varatharaj, A., & Galea, I. (2017). The blood-brain barrier in systemic inflammation. Brain, behavior, and immunity60, 1-12. https://www.sciencedirect.com/science/article/pii/S0889159116300551
7. Abbott, N. J., Patabendige, A. A., Dolman, D. E., Yusof, S. R., & Begley, D. J. (2010). Structure and function of the blood–brain barrier. Neurobiology of disease37(1), 13-25.https://www.sciencedirect.com/science/article/pii/S0969996109002083
8. Setiadi, A., Korim, W. S., Elsaafien, K., & Yao, S. T. (2018). The role of the blood–brain barrier in hypertension. Experimental physiology103(3), 337-342.https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/EP086434
9. Vairappan, B., Sundhar, M., & Srinivas, B. H. (2019). Resveratrol Restores Neuronal Tight Junction Proteins Through Correction of Ammonia and Inflammation in CCl 4-Induced Cirrhotic Mice. Molecular neurobiology56(7), 4718-4729.https://link.springer.com/article/10.1007/s12035-018-1389-x
10. Zhao, H. F., Li, N., Wang, Q., Cheng, X. J., Li, X. M., & Liu, T. T. (2015). Resveratrol decreases the insoluble Aβ1–42 level in hippocampus and protects the integrity of the blood–brain barrier in AD rats. Neuroscience310, 641-649.https://www.sciencedirect.com/science/article/pii/S0306452215009136
11. Michinaga, S., & Koyama, Y. (2017). Protection of the blood–brain barrier as a therapeutic strategy for brain damage. Biological and Pharmaceutical Bulletin40(5), 569-575.https://www.jstage.jst.go.jp/article/bpb/40/5/40_b16-00991/_article/-char/ja/
12. Ronaldson, P. T., & Davis, T. P. (2015). Targeting transporters: promoting blood–brain barrier repair in response to oxidative stress injury. Brain research1623, 39-52.https://www.sciencedirect.com/science/article/pii/S0006899315002000
13. Choi, B. H. (1993). Oxygen, antioxidants and brain dysfunction. Yonsei Medical Journal34(1), 1-10.https://www.eymj.org/search.php?where=aview&id=10.3349/ymj.1993.34.1.1&code=0069YMJ&vmode=AFTR
14. Lochhead, J. J., McCaffrey, G., Quigley, C. E., Finch, J., DeMarco, K. M., Nametz, N., & Davis, T. P. (2010). Oxidative stress increases blood–brain barrier permeability and induces alterations in occludin during hypoxia–reoxygenation. Journal of Cerebral Blood Flow & Metabolism30(9), 1625-1636. https://journals.sagepub.com/doi/abs/10.1038/jcbfm.2010.29
15. Enciu, A. M., Gherghiceanu, M., & Popescu, B. O. (2013). Triggers and effectors of oxidative stress at blood-brain barrier level: relevance for brain ageing and neurodegeneration. Oxidative medicine and cellular longevity2013.https://www.hindawi.com/journals/omcl/2013/297512/abs/ 
16. Mauro, C., De Rosa, V., Marelli-Berg, F., & Solito, E. (2015). Metabolic syndrome and the immunological affair with the blood–brain barrier. Frontiers in immunology5, 677.https://www.frontiersin.org/articles/10.3389/fimmu.2014.00677/full
17. Rempe, R. G., Hartz, A. M., & Bauer, B. (2016). Matrix metalloproteinases in the brain and blood–brain barrier: versatile breakers and makers. Journal of Cerebral Blood Flow & Metabolism36(9), 1481-1507.https://journals.sagepub.com/doi/abs/10.1177/0271678X16655551
18. Kempuraj, D., Mentor, S., Thangavel, R., Ahmed, M. E., Selvakumar, G. P., Raikwar, S. P., ... & Zaheer, A. (2019). Mast cells in stress, pain, blood-brain barrier, neuroinflammation and Alzheimer’s disease. Frontiers in cellular neuroscience13, 54.https://www.frontiersin.org/articles/10.3389/fncel.2019.00054/full
19. Won, S. M., Lee, J. H., Park, U. J., Gwag, J., Gwag, B. J., & Lee, Y. B. (2011). Iron mediates endothelial cell damage and blood-brain barrier opening in the hippocampus after transient forebrain ischemia in rats. Experimental & molecular medicine43(2), 121-128.https://www.nature.com/articles/emm201115
20. Toyokuni, S. (2014). Iron and thiols as two major players in carcinogenesis: friends or foes?. Frontiers in pharmacology5, 200.https://www.frontiersin.org/articles/10.3389/fphar.2014.00200/full
21. Lochhead, J. J., Ronaldson, P. T., & Davis, T. P. (2017). Hypoxic stress and inflammatory pain disrupt blood-brain barrier tight junctions: implications for drug delivery to the central nervous system. The AAPS journal19(4), 910-920.https://link.springer.com/article/10.1208/s12248-017-0076-6
22. Tyagi, S. C., Lominadze, D., & Roberts, A. M. (2005). Homocysteine in microvascular endothelial cell barrier permeability. Cell biochemistry and biophysics43(1), 37-44. https://link.springer.com/article/10.1385/CBB:43:1:037
23. Amourette, C., Lamproglou, I., Barbier, L., Fauquette, W., Zoppe, A., Viret, R., & Diserbo, M. (2009). Gulf War illness: Effects of repeated stress and pyridostigmine treatment on blood–brain barrier permeability and cholinesterase activity in rat brain. Behavioural brain research203(2), 207-214. https://www.sciencedirect.com/science/article/pii/S0166432809002885
24. Pizzorno, J. E., & Katzinger, J. J. (2012). Glutathione: Physiological and clinical relevance. Journal of Restorative Medicine1(1), 24-37. https://journal.restorativemedicine.org/index.php/journal/article/view/8
25. Li, W., Busu, C., Circu, M. L., & Aw, T. Y. (2012). Glutathione in cerebral microvascular endothelial biology and pathobiology: implications for brain homeostasis. International journal of cell biology2012. https://www.hindawi.com/journals/ijcb/2012/434971/abs/
26. Broux, B., Gowing, E., & Prat, A. (2015, November). Glial regulation of the blood-brain barrier in health and disease. In Seminars in immunopathology (Vol. 37, No. 6, pp. 577-590). Springer Berlin Heidelberg. https://link.springer.com/article/10.1007/s00281-015-0516-2
27. Lebda, M. A., Sadek, K. M., Tohamy, H. G., Abouzed, T. K., Shukry, M., Umezawa, M., & El-Sayed, Y. S. (2018). Potential role of α-lipoic acid and Ginkgo biloba against silver nanoparticles-induced neuronal apoptosis and blood-brain barrier impairments in rats. Life sciences212, 251-260. https://www.sciencedirect.com/science/article/pii/S0024320518306283
28. Matias, I., Buosi, A. S., & Gomes, F. C. A. (2016). Functions of flavonoids in the central nervous system: astrocytes as targets for natural compounds. Neurochemistry international95, 85-91.https://www.sciencedirect.com/science/article/pii/S0197018616300092
29. Blanchette, M., & Daneman, R. (2015). Formation and maintenance of the BBB. Mechanisms of development138, 8-16. https://www.sciencedirect.com/science/article/pii/S0925477315300095
30. Della Giustina, A., Goldim, M. P., Danielski, L. G., Florentino, D., Garbossa, L., Joaquim, L., ... & da Rosa, N. (2020). Fish oil–rich lipid emulsion modulates neuroinflammation and prevents long-term cognitive dysfunction after sepsis. Nutrition70, 110417.https://www.sciencedirect.com/science/article/pii/S0899900718309444
31. Almutairi, M. M., Gong, C., Xu, Y. G., Chang, Y., & Shi, H. (2016). Factors controlling permeability of the blood–brain barrier. Cellular and molecular life sciences73(1), 57-77. https://link.springer.com/content/pdf/10.1007/s00018-015-2050-8.pdf
32. Elwood, E., Lim, Z., Naveed, H., & Galea, I. (2017). The effect of systemic inflammation on human brain barrier function. Brain, behavior, and immunity62, 35-40.https://www.sciencedirect.com/science/article/pii/S0889159116304883
33. Sajja, R. K., Rahman, S., & Cucullo, L. (2016). Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress. Journal of Cerebral Blood Flow & Metabolism36(3), 539-554.https://journals.sagepub.com/doi/abs/10.1177/0271678X15616978
34. Patel, J. P., & Frey, B. N. (2015). Disruption in the blood-brain barrier: the missing link between brain and body inflammation in bipolar disorder?. Neural plasticity2015.https://www.hindawi.com/journals/np/2015/708306/abs/
35. Prasad, S., Sajja, R. K., Naik, P., & Cucullo, L. (2014). Diabetes mellitus and blood-brain barrier dysfunction: an overview. Journal of pharmacovigilance2(2), 125.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306190/
36. Obermeier, B., Daneman, R., & Ransohoff, R. M. (2013). Development, maintenance and disruption of the blood-brain barrier. Nature medicine19(12), 1584. https://www.nature.com/articles/nm.3407.pdf?origin=ppub
37. Kuhlmann, C. R., Librizzi, L., Closhen, D., Pflanzner, T., Lessmann, V., Pietrzik, C. U., ... & Luhmann, H. J. (2009). Mechanisms of C-reactive protein-induced blood-brain barrier disruption. Stroke40(4), 1458.http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.553.5906&rep=rep1&type=pdf
38. Veerhuis, R., Nielsen, H. M., & Tenner, A. J. (2011). Complement in the brain. Molecular immunology48(14), 1592-1603.https://www.sciencedirect.com/science/article/pii/S0161589011001209
39. Jacob, A., & Alexander, J. J. (2014). Complement and blood–brain barrier integrity. Molecular immunology61(2), 149-152.https://www.sciencedirect.com/science/article/pii/S0161589014001709
40. Bested, A. C., Saunders, P. R., & Logan, A. C. (2001). Chronic fatigue syndrome: neurological findings may be related to blood–brain barrier permeability. Medical hypotheses57(2), 231-237.https://www.sciencedirect.com/science/article/pii/S0306987701913064
41. Bested, A. C., Saunders, P. R., & Logan, A. C. (2001). Chronic fatigue syndrome: neurological findings may be related to blood–brain barrier permeability. Medical hypotheses57(2), 231-237.https://www.sciencedirect.com/science/article/pii/S0306987701913064
42. Hyde, J. A. (2017). Borrelia burgdorferi keeps moving and carries on: a review of borrelial dissemination and invasion. Frontiers in immunology8, 114.https://www.frontiersin.org/articles/10.3389/fimmu.2017.00114/full
43. Engelhardt, S., Patkar, S., & Ogunshola, O. O. (2014). Cell‐specific blood–brain barrier regulation in health and disease: a focus on hypoxia. British journal of pharmacology171(5), 1210-1230.https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.12489
44. Risau, W., Dingler, A., Albrecht, U., Dehouck, M. P., & Cecchelli, R. (1992). Blood–Brain Barrier Pericytes Are the Main Source of γ‐Glutamyltranspeptidase Activity in Brain Capillaries. Journal of neurochemistry58(2), 667-672.https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1471-4159.1992.tb09769.x
45. Ballabh, P., Braun, A., & Nedergaard, M. (2004). The blood–brain barrier: an overview: structure, regulation, and clinical implications. Neurobiology of disease16(1), 1-13.https://www.sciencedirect.com/science/article/pii/S0969996103002833
46. Banks, W. A. (2015). The blood-brain barrier in neuroimmunology: tales of separation and assimilation. Brain, behavior, and immunity44, 1-8.https://www.sciencedirect.com/science/article/pii/S0889159114004243
47. Bogush, M., Heldt, N. A., & Persidsky, Y. (2017). Blood brain barrier injury in diabetes: unrecognized effects on brain and cognition. Journal of Neuroimmune Pharmacology12(4), 593-601.https://link.springer.com/article/10.1007/s11481-017-9752-7
48. Rhea, E. M., Salameh, T. S., Logsdon, A. F., Hanson, A. J., Erickson, M. A., & Banks, W. A. (2017). Blood-brain barriers in obesity. The AAPS journal19(4), 921-930.https://link.springer.com/article/10.1208/s12248-017-0079-3
49. Alluri, H., Wiggins-Dohlvik, K., Davis, M. L., Huang, J. H., & Tharakan, B. (2015). Blood–brain barrier dysfunction following traumatic brain injury. Metabolic brain disease30(5), 1093-1104.https://link.springer.com/article/10.1007/s11011-015-9651-7
50. Jiang, X., Andjelkovic, A. V., Zhu, L., Yang, T., Bennett, M. V., Chen, J., ... & Shi, Y. (2018). Blood-brain barrier dysfunction and recovery after ischemic stroke. Progress in neurobiology163, 144-171.https://www.sciencedirect.com/science/article/pii/S0301008216301733
51. Takechi, R., Lam, V., Brook, E., Giles, C., Fimognari, N., Mooranian, A., ... & Mamo, J. C. (2017). Blood-brain barrier dysfunction precedes cognitive decline and neurodegeneration in diabetic insulin resistant mouse model: an implication for causal link. Frontiers in aging neuroscience9, 399.https://www.frontiersin.org/articles/10.3389/fnagi.2017.00399/full
52. Alexander, J. J. (2018). Blood-brain barrier (BBB) and the complement landscape. Molecular immunology102, 26-31.https://www.sciencedirect.com/science/article/pii/S0161589018304723
53. Della Giustina, A., Goldim, M. P., Danielski, L. G., Florentino, D., Mathias, K., Garbossa, L., ... & Laurentino, A. O. M. (2017). Alpha-lipoic acid attenuates acute neuroinflammation and long-term cognitive impairment after polymicrobial sepsis. Neurochemistry international108, 436-447.https://www.sciencedirect.com/science/article/pii/S0197018617301213
54. Montagne, A., Zhao, Z., & Zlokovic, B. V. (2017). Alzheimer’s disease: A matter of blood–brain barrier dysfunction?. The Journal of experimental medicine214(11), 3151-3169.https://rupress.org/jem/article-abstract/214/11/3151/42256
55. Keaney, J., & Campbell, M. (2015). The dynamic blood–brain barrier. The FEBS journal282(21), 4067-4079.https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.13412@10.1111/(ISSN)1742-4658.Neurobio2016

Evaluation of neuroinflammation in a clinical setting

1. Raz, N., Yang, Y., Dahle, C. L., & Land, S. (2012). Volume of white matter hyperintensities in healthy adults: contribution of age, vascular risk factors, and inflammation-related genetic variants. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease1822(3), 361-369.https://www.sciencedirect.com/science/article/pii/S092544391100189X
2. Pulli, B., & Chen, J. W. (2014). Imaging neuroinflammation–from bench to bedside. Journal of clinical & cellular immunology5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266918/

 

 

 

 

Frequently Asked Questions

What is the average delivery time?

All of our products are manufactured with care in Europe and shipped out of Germany. Within Europe, the average shipping time is 2-5 working days with Express Shipping and 5-10 working days with Standard shipping. Due to COVID-19, there might be some unexpected carrier delays. 

How do I know if these supplements actually work?

Our supplements are backed by years of research by a team of neurologists and specialists in the health care industry. We want to make sure to deliver the highest quality possible and create products that actually work. See our References to check out the sources that have been used during the production process of our supplements. 

Can I take these supplements during pregnancy?

Our supplement is 100% natural and medicine-free. However, we recommend to always consult your doctor before taking any dietary supplements whilst pregnant (or planning to be). 

Can I pay with something else than Paypal?

If you prefer using a different payment method, you can transfer the product total + €10 standard shipping costs to:

IBAN: CY91 0020 0195 0000 3570 3530 5527

Account Name: Brain Rehab Distribution Limited

❗️Make sure to put your name in the payment description, and to send us an e-mail at info@brainandspine.rehab letting us know about your order.

Can I take these supplements whilst on birth control?

Please always consult with your health care professional before taking any supplement whilst on prescription medication. 

Do I need to follow a specific diet for these supplements to work?

We definitely recommend to keep a healthy diet, work out regularly and make sure to get enough sleep for optimal results of our product. As science shows, a balanced lifestyle combined with high quality supplements can actually result in improvements.   

How long does a bottle last?

One bottle of Repair & Protect contains 180 capsules. Our average recommended daily intake is 1-3 capsules daily (with a meal), and could be increased (in extreme cases) all the way up to six capsules per day. Therefore, a bottle lasts a month on average. 

Are your products natural?

All of our supplements have been tested thoroughly and are 100% natural. They consist of vitamins, minerals and more ingredients that are proven to improve brain health. 

Are the supplements allergy-proof?

Our Repair & Protect formula does not contain any gluten, milk, or nuts. There is no artificial flavouring or smell added. Lastly, there are no added sugars. 

Where do I keep the bottle in my house? In which temperature?

This product has to be kept out of direct sunlight and is best to be kept in room temperature (23C or 73F). 

What is brain.rehab exactly?

This company, Brainrescue, is part of Brain.rehab (www.brain.rehab), which was founded by a stroke survivor and a functional neurologist. Together, they strive to make the world a better place for brain-injured people. Their mission is to deliver customised training and help for people with brain trauma. The importance of dietary supplements and food is extremely significant in this process. After years of research and development, our team of health care professionals has come up with several supplement formulas that actually work. Check out the About Us page for more information about the founders.