1. Kandle ER. The Brain/Immune Connection: Progress Report on Brain Research.. New York: The Dana Aliance for Brain Initiatives; 2004.
2. World Health Organization (WHO). Neurological Disorders: Public health challenges. Geneva: WHO Press; 2006.
3. Olesen J, Gustavsson A, Svensson M, Wittchen HU, Jönsson B; CDBE2010 study group; European Brain Council. The economic cost of brain disorders in Europe. Eur J Neurol. 2012;19(1):155-62. doi: 10.1111/j.1468-1331.2011.03590.x.
4. GBD 2015 Neurological Disorders Collaborator Group. Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. 2017;16(11):877-97. doi: 10.1016/S1474-4422(17)30299-5.
5. Neuman J. Ueber das Vorkommen der sogneannten “Mastzellen” bei pathologischen Veraenderungen des Gehirns. Arch Pathol Anat Physiol Virchows. 1890;122:378-81.
6. Olsson Y. Mast cells in plaques of multiple sclerosis. Acta Neurol Scand. 1974;50(5):611-8. doi: 10.1111/j.1600-0404.1974.tb02806.x.
7. Shan L, Bao AM, Swaab DF. The human histaminergic system in neuropsychiatric disorders. Trends Neurosci. 2015;38(3):167-77. doi: 10.1016/j.tins.2014.12.008.
8. Haas H, Panula P. The role of histamine and the tuberomamillary nucleus in the nervous system. Nat Rev Neurosci. 2003;4(2):121-30. doi: 10.1038/nrn1034.
9. Brady S, Siegel G, Albers RW, Price D. Basic Neurochemistry: Principles of Molecular, Cellular, and Medical Neurobiology 8th ed. Academic Press; 2011.
10. Riedel G, Platt B. From Messengers to Molecules: Memories are Made of These. Springer Science & Business Media; 2004.
11. Giannoni P, Passani MB, Nosi D, Chazot PL, Shenton FC, Medhurst AD, et al. Heterogeneity of histaminergic neurons in the tuberomammillary nucleus of the rat. Eur J Neurosci. 2009;29(12):2363-74. doi: 10.1111/j.1460-9568.2009.06765.x.
12. Shahid M, Tripathi T, Sobia F, Moin S, Siddiqui M, Khan RA. Histamine, Histamine Receptors, and their Role in Immunomodulation: An Updated Systematic Review. Open Immunol J. 2009;2:9-41. doi: 10.2174/1874226200902010009.
13. Mazurkiewicz-Kwilecki IM, Nsonwah S. Changes in the regional brain histamine and histidine levels in postmortem brains of Alzheimer patients. Can J Physiol Pharmacol. 1989;67(1):75-8. doi: 10.1139/y89-013.
14. Costanza M, Colombo MP, Pedotti R. Mast cells in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis. Int J Mol Sci. 2012 16;13(11):15107-25. doi: 10.3390/ijms131115107.
15. Khalil M, Ronda J, Weintraub M, Jain K, Silver R, Silverman AJ. Brain mast cell relationship to neurovasculature during development. Brain Res. 2007 26;1171:18-29. doi: 10.1016/j.brainres.2007.07.034.
16. Michaloudi H, Batzios C, Chiotelli M, Papadopoulos GC. Developmental changes of mast cell populations in the cerebral meninges of the rat. J Anat. 2007;211(4):556-66. doi: 10.1111/j.1469-7580.2007.00795.x.
17. Hendrix S, Warnke K, Siebenhaar F, Peters EM, Nitsch R, Maurer M. The majority of brain mast cells in B10.PL mice is present in the hippocampal formation. Neurosci Lett. 2006;392(3):174-7. doi: 10.1016/j.neulet.2005.09.029.
18. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-241. doi: 10.1152/physrev.00043.2007.
19. Zhuang X, Silverman AJ, Silver R. Brain mast cell degranulation regulates blood-brain barrier. J Neurobiol. 1996;31(4):393-403. doi: 10.1002/(SICI)1097-4695(199612)31:4<393::AID-NEU1>3.0.CO;2-4.
20. Matsumoto I, Inoue Y, Shimada T, Aikawa T. Brain mast cells act as an immune gate to the hypothalamic-pituitary-adrenal axis in dogs. J Exp Med. 2001;194(1):71-8. doi: 10.1084/jem.194.1.71.
21. Matsumoto I, Inoue Y, Shimada T, Matsunaga T, Aikawa T. Stimulation of brain mast cells by compound 48/80, a histamine liberator, evokes renin and vasopressin release in dogs. Am J Physiol Regul Integr Comp Physiol. 2008;294(3):R689-98. doi: 10.1152/ajpregu.00453.2007.
22. Bianco AC, Nunes MT, Douglas CR. Influence of mast cells on thyroid function. Endocrinol Exp. 1983;17(2):99-106.
23. Khalil MH, Silverman AJ, Silver R. Mast cells in the rat brain synthesize gonadotropin-releasing hormone. J Neurobiol. 2003;56(2):113-24. doi: 10.1002/neu.10220.
24. Wilhelm M, King B, Silverman AJ, Silver R. Gonadal steroids regulate the number and activational state of mast cells in the medial habenula. Endocrinology. 2000;141(3):1178-86. doi: 10.1210/endo.141.3.7352.
25. Silverman AJ, Sutherland AK, Wilhelm M, Silver R. Mast cells migrate from blood to brain. J Neurosci. 2000;20(1):401-8. doi: 10.1523/JNEUROSCI.20-01-00401.2000.
26. Monteforte R, Pinelli C, Santillo A, Rastogi RK, Polese G, Baccari GC. Mast cell population in the frog brain: distribution and influence of thyroid status. J Exp Biol. 2010;213(Pt 10):1762-70. doi: 10.1242/jeb.039628. PMID: 20435827.
27. Van Op den bosch J, Van Nassauw L, Van Marck E, Timmermans JP. Somatostatin modulates mast cell-induced responses in murine spinal neurons and satellite cells. Am J Physiol Gastrointest Liver Physiol. 2009;297(2):G406-17. doi: 10.1152/ajpgi.00059.2009.
28. Leon A, Buriani A, Dal Toso R, Fabris M, Romanello S, Aloe L, et al. Mast cells synthesize, store, and release nerve growth factor. Proc Natl Acad Sci U S A. 1994;91(9):3739-43. doi: 10.1073/pnas.91.9.3739.
29. Rozniecki JJ, Hauser SL, Stein M, Lincoln R, Theoharides TC. Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients. Ann Neurol. 1995;37(1):63-6. doi: 10.1002/ana.410370112.
30. Bennett JL, Blanchet MR, Zhao L, Zbytnuik L, Antignano F, Gold M, et al. Bone marrow-derived mast cells accumulate in the central nervous system during inflammation but are dispensable for experimental autoimmune encephalomyelitis pathogenesis. J Immunol. 2009;182(9):5507-14. doi: 10.4049/jimmunol.0801485.
31. Tanzola MB, Robbie-Ryan M, Gutekunst CA, Brown MA. Mast cells exert effects outside the central nervous system to influence experimental allergic encephalomyelitis disease course. J Immunol. 2003;171(8):4385-91. doi: 10.4049/jimmunol.171.8.4385.
32. Kim DY, Hong GU, Ro JY. Signal pathways in astrocytes activated by cross-talk between of astrocytes and mast cells through CD40-CD40L. J Neuroinflammation. 2011;8:25. doi: 10.1186/1742-2094-8-25.
33. Sayed BA, Walker ME, Brown MA. Cutting edge: mast cells regulate disease severity in a relapsing-remitting model of multiple sclerosis. J Immunol. 2011;186(6):3294-8. doi: 10.4049/jimmunol.1003574.
34. Kim DY, Jeoung D, Ro JY. Signaling pathways in the activation of mast cells cocultured with astrocytes and colocalization of both cells in experimental allergic encephalomyelitis. J Immunol. 2010;185(1):273-83. doi: 10.4049/jimmunol.1000991.
35. Christy AL, Walker ME, Hessner MJ, Brown MA. Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE. J Autoimmun. 2013;42:50-61. doi: 10.1016/j.jaut.2012.11.003.
36. Walker-Caulfield ME, Hatfield JK, Brown MA. Dynamic changes in meningeal inflammation correspond to clinical exacerbations in a murine model of relapsing-remitting multiple sclerosis. J Neuroimmunol. 2015;278:112-22. doi: 10.1016/j.jneuroim.2014.12.009.
37. Piconese S, Costanza M, Musio S, Tripodo C, Poliani PL, Gri G, et al. Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit W-sh/W-sh mice. Lab Invest. 2011;91(4):627-41. doi: 10.1038/labinvest.2011.3.
38. Mayo L, Quintana FJ, Weiner HL. The innate immune system in demyelinating disease. Immunol Rev. 2012;248(1):170-87. doi: 10.1111/j.1600-065X.2012.01135.x.
39. Vermersch P, Benrabah R, Schmidt N, Zéphir H, Clavelou P, Vongsouthi C, et al. Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study. BMC Neurol. 2012;12:36. doi: 10.1186/1471-2377-12-36.
40. Förster A, Preussner LM, Seeger JM, Rabenhorst A, Kashkar H, Mrowietz U, et al. Dimethylfumarate induces apoptosis in human mast cells. Exp Dermatol. 2013;22(11):719-24. doi: 10.1111/exd.12247.
41. Kritas SK, Saggini A, Cerulli G, Caraffa A, Antinolfi P, Pantalone A, et al. Impact of mast cells on multiple sclerosis: inhibitory effect of natalizumab. Int J Immunopathol Pharmacol. 2014;27(3):331-5. doi: 10.1177/039463201402700303.
42. Kawamata T, Akiyama H, Yamada T, McGeer PL. Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol. 1992;140(3):691-707.
43. Fiala M, Chattopadhay M, La Cava A, Tse E, Liu G, Lourenco E, et al. IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients. J Neuroinflammation. 2010;7:76. doi: 10.1186/1742-2094-7-76.
44. Mizwicki MT, Fiala M, Magpantay L, Aziz N, Sayre J, Liu G, et al. Tocilizumab attenuates inflammation in ALS patients through inhibition of IL6 receptor signaling. Am J Neurodegener Dis. 2012;1(3):305-15.
45. Apolloni S, Fabbrizio P, Parisi C, Amadio S, Volonté C. Clemastine Confers Neuroprotection and Induces an Anti-Inflammatory Phenotype in SOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis. Mol Neurobiol. 2016;53(1):518-31. doi: 10.1007/s12035-014-9019-8.
46. Clemente S. Amyotrophic lateral sclerosis treatment with ultramicronized palmitoylethanolamide: a case report. CNS Neurol Disord Drug Targets. 2012;11(7):933-6. doi: 10.2174/1871527311201070933.
47. Panula P, Rinne J, Kuokkanen K, Eriksson KS, Sallmen T, Kalimo H, et al. Neuronal histamine deficit in Alzheimer's disease. Neuroscience. 1998;82(4):993-7. doi: 10.1016/s0306-4522(97)00353-9.
48. Motawaj M, Peoc'h K, Callebert J, Arrang JM. CSF levels of the histamine metabolite tele-methylhistamine are only slightly decreased in Alzheimer's disease. J Alzheimers Dis. 2010;22(3):861-71. doi: 10.3233/JAD-2010-100381.
49. Niederhoffer N, Levy R, Sick E, Andre P, Coupin G, Lombard Y, et al. Amyloid beta peptides trigger CD47-dependent mast cell secretory and phagocytic responses. Int J Immunopathol Pharmacol. 2009;22(2):473-83. doi: 10.1177/039463200902200224.
50. Nelson RB, Siman R, Iqbal MA, Potter H. Identification of a chymotrypsin-like mast cell protease in rat brain capable of generating the N-terminus of the Alzheimer amyloid beta-protein. J Neurochem. 1993;61(2):567-77. doi: 10.1111/j.1471-4159.1993.tb02160.x.
51. Kalsheker NA. Alpha 1-antichymotrypsin. Int J Biochem Cell Biol. 1996;28(9):961-4. doi: 10.1016/1357-2725(96)00032-5.
52. Folch J, Petrov D, Ettcheto M, Pedrós I, Abad S, Beas-Zarate C, et al. Masitinib for the treatment of mild to moderate Alzheimer's disease. Expert Rev Neurother. 2015;15(6):587-96. doi: 10.1586/14737175.2015.1045419.
53. Piette F, Belmin J, Vincent H, Schmidt N, Pariel S, Verny M, et al. Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: a randomised, placebo-controlled phase 2 trial. Alzheimers Res Ther. 2011;3(2):16. doi: 10.1186/alzrt75.
54. Moura DS, Sultan S, Georgin-Lavialle S, Pillet N, Montestruc F, Gineste P, et al. Depression in patients with mastocytosis: prevalence, features and effects of masitinib therapy. PLoS One. 2011;6(10):e26375. doi: 10.1371/journal.pone.0026375.
55. Angelidou A, Francis K, Vasiadi M, Alysandratos KD, Zhang B, Theoharides A, et al. Neurotensin is increased in serum of young children with autistic disorder. J Neuroinflammation. 2010;7:48. doi: 10.1186/1742-2094-7-48.
56. Theoharides TC, Angelidou A, Alysandratos KD, Zhang B, Asadi S, Francis K, et al. Mast cell activation and autism. Biochim Biophys Acta. 2012;1822(1):34-41. doi: 10.1016/j.bbadis.2010.12.017.
57. Theoharides TC, Zhang B. Neuro-inflammation, blood-brain barrier, seizures and autism. J Neuroinflammation. 2011;8:168. doi: 10.1186/1742-2094-8-168.
58. Theoharides TC, Asadi S, Patel AB. Focal brain inflammation and autism. J Neuroinflammation. 2013;10:46. doi: 10.1186/1742-2094-10-46.
59. Nishino S, Sakurai E, Nevsimalova S, Yoshida Y, Watanabe T, Yanai K, et al. Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls. Sleep. 2009;32(2):175-80. doi: 10.1093/sleep/32.2.175.
60. Xanthos DN, Gaderer S, Drdla R, Nuro E, Abramova A, Ellmeier W, et al. Central nervous system mast cells in peripheral inflammatory nociception. Mol Pain. 2011;7:42. doi: 10.1186/1744-8069-7-42.
61. Lindsberg PJ, Strbian D, Karjalainen-Lindsberg ML. Mast cells as early responders in the regulation of acute blood-brain barrier changes after cerebral ischemia and hemorrhage. J Cereb Blood Flow Metab. 2010;30(4):689-702. doi: 10.1038/jcbfm.2009.282.
62. Strbian D, Karjalainen-Lindsberg ML, Kovanen PT, Tatlisumak T, Lindsberg PJ. Mast cell stabilization reduces hemorrhage formation and mortality after administration of thrombolytics in experimental ischemic stroke. Circulation. 2007;116(4):411-8. doi: 10.1161/CIRCULATIONAHA.106.655423.
63. Jin Y, Silverman AJ, Vannucci SJ. Mast cell stabilization limits hypoxic-ischemic brain damage in the immature rat. Dev Neurosci. 2007;29(4-5):373-84. doi: 10.1159/000105478.
64. Strbian D, Karjalainen-Lindsberg ML, Tatlisumak T, Lindsberg PJ. Cerebral mast cells regulate early ischemic brain swelling and neutrophil accumulation. J Cereb Blood Flow Metab. 2006;26(5):605-12. doi: 10.1038/sj.jcbfm.9600228.
65. Arac A, Grimbaldeston MA, Nepomuceno AR, Olayiwola O, Pereira MP, Nishiyama Y, et al. Evidence that meningeal mast cells can worsen stroke pathology in mice. Am J Pathol. 2014;184(9):2493-504. doi: 10.1016/j.ajpath.2014.06.003.
66. Jin Y, Silverman AJ, Vannucci SJ. Mast cells are early responders after hypoxia-ischemia in immature rat brain. Stroke. 2009;40(9):3107-12. doi: 10.1161/STROKEAHA.109.549691.
67. Strbian D, Tatlisumak T, Ramadan UA, Lindsberg PJ. Mast cell blocking reduces brain edema and hematoma volume and improves outcome after experimental intracerebral hemorrhage. J Cereb Blood Flow Metab. 2007;27(4):795-802. doi: 10.1038/sj.jcbfm.9600387.
68. Abrams MB, Nilsson I, Lewandowski SA, Kjell J, Codeluppi S, Olson L, et al. Imatinib enhances functional outcome after spinal cord injury. PLoS One. 2012;7(6):e38760. doi: 10.1371/journal.pone.0038760.
69. Nelissen S, Vangansewinkel T, Geurts N, Geboes L, Lemmens E, Vidal PM, et al. Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4. Neurobiol Dis. 2014;62:260-72. doi: 10.1016/j.nbd.2013.09.012.
70. Hendrix S, Kramer P, Pehl D, Warnke K, Boato F, Nelissen S, et al. Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4. FASEB J. 2013;27(3):920-9. doi: 10.1096/fj.12-204800.
71. Stokely ME, Orr EL. Acute effects of calvarial damage on dural mast cells, pial vascular permeability, and cerebral cortical histamine levels in rats and mice. J Neurotrauma. 2008;25(1):52-61. doi: 10.1089/neu.2007.0397.
72. Valle-Dorado MG, Santana-Gómez CE, Orozco-Suárez SA, Rocha L. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus. Neuropharmacology. 2015;92:49-55. doi: 10.1016/j.neuropharm.2014.12.032.
73. Yillar DO, Küçükhüseyin C. The effects of compound 48/80, morphine, and mast cell depletion on electroshock seizure in mice. J Basic Clin Physiol Pharmacol. 2008;19(1):1-14. doi: 10.1515/jbcpp.2008.19.1.1.
74. Rehni AK, Singh TG, Singh N, Arora S. Tramadol-induced seizurogenic effect: a possible role of opioid-dependent histamine H1 receptor activation-linked mechanism. Naunyn Schmiedebergs Arch Pharmacol. 2010;381(1):11-9. doi: 10.1007/s00210-009-0476-y.
75. Swiader M, Wielosz M, Czuczwar SJ. Interaction of astemizole, an H1 receptor antagonist, with conventional antiepileptic drugs in mice. Pharmacol Biochem Behav. 2003;76(1):169-78. doi: 10.1016/s0091-3057(03)00212-0.
76. Yokoyama H, Onodera K, Iinuma K, Watanabe T. 2-Thiazolylethylamine, a selective histamine H1 agonist, decreases seizure susceptibility in mice. Pharmacol Biochem Behav. 1994;47(3):503-7. doi: 10.1016/0091-3057(94)90151-1.
77. Yokoyama H, Onodera K, Maeyama K, Sakurai E, Iinuma K, Leurs R, et al. Clobenpropit (VUF-9153), a new histamine H3 receptor antagonist, inhibits electrically induced convulsions in mice. Eur J Pharmacol. 1994;260(1):23-8. doi: 10.1016/0014-2999(94)90005-1.
78. Põlajeva J, Sjösten AM, Lager N, Kastemar M, Waern I, Alafuzoff I, et al. Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12. PLoS One. 2011;6(9):e25222. doi: 10.1371/journal.pone.0025222.
79. Põlajeva J, Bergström T, Edqvist PH, Lundequist A, Sjösten A, Nilsson G, et al. Glioma-derived macrophage migration inhibitory factor (MIF) promotes mast cell recruitment in a STAT5-dependent manner. Mol Oncol. 2014;8(1):50-8. doi: 10.1016/j.molonc.2013.09.002.
80. Yang FC, Ingram DA, Chen S, Hingtgen CM, Ratner N, Monk KR, et al. Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells. J Clin Invest. 2003;112(12):1851-61. doi: 10.1172/JCI19195.
81. Yang FC, Ingram DA, Chen S, Zhu Y, Yuan J, Li X, et al. Nf1-dependent tumors require a microenvironment containing Nf1+/-- and c-kit-dependent bone marrow. Cell. 2008;135(3):437-48. doi: 10.1016/j.cell.2008.08.041.
82. Staser K, Yang FC, Clapp DW. Mast cells and the neurofibroma microenvironment. Blood. 2010;116(2):157-64. doi: 10.1182/blood-2009-09-242875.
83. Sharma MC, Ralte AM, Gaekwad S, Santosh V, Shankar SK, Sarkar C. Subependymal giant cell astrocytoma--a clinicopathological study of 23 cases with special emphasis on histogenesis. Pathol Oncol Res. 2004;10(4):219-24. doi: 10.1007/BF03033764.
84. Broholm H, Laursen H. Vascular endothelial growth factor (VEGF) receptor neuropilin-1's distribution in astrocytic tumors. APMIS. 2004;112(4-5):257-63. doi: 10.1111/j.1600-0463.2004.apm11204-0505.x.
85. Maślińska D, Woźniak R, Kaliszek A, Schmidt-Sidor B, Lipska A, Woolley DE. Phenotype of mast cells in the brain tumor. Capillary hemangioblastoma. Folia Neuropathol. 1999;37(3):138-42.
86. Reszec J, Hermanowicz A, Kochanowicz J, Turek G, Mariak Z, Chyczewski L. Mast cells evaluation in meningioma of various grades. Folia Histochem Cytobiol. 2012;50(4):542-6. doi: 10.5603/14744.
87. Reszec J, Hermanowicz A, Rutkowski R, Bernaczyk P, Mariak Z, Chyczewski L. Evaluation of mast cells and hypoxia inducible factor-1 expression in meningiomas of various grades in correlation with peritumoral brain edema. J Neurooncol. 2013;115(1):119-25. doi: 10.1007/s11060-013-1208-1.
88. Tirakotai W, Mennel HD, Celik I, Hellwig D, Bertalanffy H, Riegel T. Secretory meningioma: immunohistochemical findings and evaluation of mast cell infiltration. Neurosurg Rev. 2006;29(1):41-8. doi: 10.1007/s10143-005-0402-9.
89. Theoharides TC, Rozniecki JJ, Sahagian G, Jocobson S, Kempuraj D, Conti P, et al. Impact of stress and mast cells on brain metastases. J Neuroimmunol. 2008;205(1-2):1-7. doi: 10.1016/j.jneuroim.2008.09.014.
90. Rozniecki JJ, Sahagian GG, Kempuraj D, Tao K, Jocobson S, Zhang B, et al. Brain metastases of mouse mammary adenocarcinoma is increased by acute stress. Brain Res. 2010;1366:204-10. doi: 10.1016/j.brainres.2010.09.085.