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Sensory circumventricular organs in health and disease

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Abstract

Circumventricular organs (CVOs) are specialized brain structures located around the third and fourth ventricles. They differ from the rest of the brain parenchyma in that they are highly vascularised areas that lack a blood–brain barrier. These neurohaemal organs are classified as “sensory”, when they contain neurons that can receive chemical inputs from the bloodstream. This review focuses on the sensory CVOs to describe their unique structure, and their functional roles in the maintenance of body fluid homeostasis and cardiovascular regulation, and in the generation of central acute immune and febrile responses. In doing so, the main neural connections to visceral regulatory centres such as the hypothalamus, the medulla oblongata and the endocrine hypothalamic-pituitary axis, as well as some of the relevant chemical substances involved, are described. The CVOs are vulnerable to circulating pathogens and can be portals for their entry in the brain. This review highlights recent investigations that show that the CVOs and related structures are involved in pathological conditions such as sepsis, stress, trypanosomiasis, autoimmune encephalitis, systemic amyloidosis and prion infections, while detailed information on their role in other neurodegenerative diseases such as Alzheimer’s disease or multiple sclerosis is lacking. It is concluded that studies of the CVOs and related structures may help in the early diagnosis and treatment of such disorders.

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References

  1. Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev Neurosci 7:41–53

    Article  CAS  PubMed  Google Scholar 

  2. Abelson JL, Khan S, Liberzon I, Young EA (2007) HPA axis activity in patients with panic disorder: review and synthesis of four studies. Depress Anxiety 24:66–76

    Article  PubMed  Google Scholar 

  3. Akert K, Potter HD, Anderson JW (1961) The subfornical organ in mammals. J Comp Neurol 116:1–14

    Article  CAS  PubMed  Google Scholar 

  4. Akiyama H, Barger S, Barnum S et al (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421

    Article  CAS  PubMed  Google Scholar 

  5. Akrout N, Sharshar T, Annane D (2009) Mechanisms of brain signaling during sepsis. Curr Neuropharmacol 7:296–301

    Article  CAS  PubMed  Google Scholar 

  6. Allen AM, Oldfield BJ, Giles ME (2000) Localization of angiotensin receptors in the nervous sytem. In: Quirion R, Björklund A, Hökfelt T et al (eds) Peptide receptors, Part 1, vol 16. Elsevier Science, Amsterdam., pp 79–124

    Chapter  Google Scholar 

  7. Anderson JW, Washburn DL, Ferguson AV (2000) Intrinsic osmosensitivity of subfornical organ neurons. Neuroscience 100:539–547

    Article  CAS  PubMed  Google Scholar 

  8. Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365:63–78

    Article  CAS  PubMed  Google Scholar 

  9. Bailey JD, Berardinelli JG, Rocke TE, Bessen RA (2008) Prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases. J Endocrinol 197:251–263

    Article  CAS  PubMed  Google Scholar 

  10. Barash JA (2008) Do midlife hormonal changes play a role in the onset of sporadic Creutzfeldt–Jakob disease? An epidemiologic perspective. Med Hypotheses 71:611–612

    Article  CAS  PubMed  Google Scholar 

  11. Beck E, Daniel PM (1969) Degenerative diseases of the central nervous system transmissible to experimental animals. Postgrad Med J 45:361–370

    Article  CAS  PubMed  Google Scholar 

  12. Beck E, Daniel PM, Parry HB (1964) Degeneration of the cerebellar and hypothalamoneurohypophysial systems in sheep with scrapie; and its relationship to human system degenerations. Brain 87:153–176

    Article  CAS  PubMed  Google Scholar 

  13. Behnsen G (1927) Über die Farbstoffspeicherung im Zentralnervensystem der weißen Maus in verschiedenen Alterszuständen. Z Zellforsch 4:515–572

    Article  Google Scholar 

  14. Bennett L, Yang M, Enikolopov G, Iacovitti L (2009) Circumventricular organs: a novel site of neural stem cells in the adult brain. Mol Cell Neurosci 41:337–347

    Article  CAS  PubMed  Google Scholar 

  15. Bianchi C, Gutkowska J, Ballak M et al (1986) Radioautographic localization of 125I-atrial natriuretic factor binding sites in the brain. Neuroendocrinology 44:365–372

    Article  CAS  PubMed  Google Scholar 

  16. Broadwell RD, Balin BJ, Salcman M, Kaplan RS (1983) Brain–blood barrier? Yes and no. Proc Natl Acad Sci USA 80:7352–7356

    Article  CAS  PubMed  Google Scholar 

  17. Buller KM (2001) Circumventricular organs: gateways to the brain. Role of circumventricular organs in pro-inflammatory cytokine-induced activation of the hypothalamic-pituitary-adrenal axis. Clin Exp Pharmacol Physiol 28:581–589

    Article  CAS  PubMed  Google Scholar 

  18. Camacho A, Phillips MI (1981) Horseradish peroxidase study in rat of the neural connections of the organum vasculosum of the lamina terminalis. Neurosci Lett 25:201–204

    Article  CAS  PubMed  Google Scholar 

  19. Carpenter DO, Briggs DB, Knox AP, Strominger N (1988) Excitation of the area postrema neurons by transmitters, peptides, and cyclic nucleotides. J Neurophysiol 59:358–369

    CAS  PubMed  Google Scholar 

  20. Ceccatelli S, Fahrenkrug J, Villar MJ, Hokfelt T (1991) Vasoactive intestinal polypeptide/peptide histidine isoleucine immunoreactive neuron systems in the basal hypothalamus of the rat with special reference to the portal vasculature: an immunohistochemical and in situ hybridization study. Neuroscience 43:483–502

    Article  CAS  PubMed  Google Scholar 

  21. Chernicky CL, Barnes KL, Ferrario CM, Conomy JP (1983) Brainstem distribution of neurons with efferent projections in the cervical vagus of the dog. Brain Res Bull 10:345–351

    Article  CAS  PubMed  Google Scholar 

  22. Ciriello J, Gutman MB (1991) Functional identification of central pressor pathways originating in the subfornical organ. Can J Physiol Pharmacol 69:1035–1045

    CAS  PubMed  Google Scholar 

  23. Ciriello J, Hrycyshyn AW, Calaresu FR (1981) Glossopharyngeal and vagal afferent projections to the brain stem of the cat: a horseradish peroxidase study. J Auton Nerv Syst 4:63–79

    Article  CAS  PubMed  Google Scholar 

  24. Contreras RJ, Beckstead RM, Norgren R (1982) The central projections of the trigeminal, facial, glossopharyngeal and vagus nerves: an autoradiographic study in the rat. J Auton Nerv Syst 6:303–322

    Article  CAS  PubMed  Google Scholar 

  25. Cotrell GT, Ferguson AV (2004) Sensory circumventricular organs: central roles in integrated autonomic regulation. Regul Pept 117:11–23

    Article  CAS  Google Scholar 

  26. Cunningham C, Campion S, Lunnon K et al (2009) Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry 65:304–312

    Article  CAS  PubMed  Google Scholar 

  27. Cunningham ET Jr, Miselis RR, Sawchenko PE (1994) The relationship of efferent projections from the area postrema to vagal motor and brain stem catecholamine-containing cell groups: an axonal transport and immunohistochemical study in the rat. Neuroscience 58:635–648

    Article  PubMed  Google Scholar 

  28. Dantzer R (2001) Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun 15:7–24

    Article  CAS  PubMed  Google Scholar 

  29. Dantzer R, Konsman JP, Bluthe RM, Kelley KW (2000) Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent? Auton Neurosci 85:60–65

    Article  CAS  PubMed  Google Scholar 

  30. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–56

    Article  CAS  PubMed  Google Scholar 

  31. Dellmann HD (1998) Structure of the subfornical organ: a review. Microsc Res Tech 41:85–97

    Article  CAS  PubMed  Google Scholar 

  32. Dellmann HD, Simpson J (1979) The subfornical organ. Int Rev Cytol 58:333–421

    Article  CAS  PubMed  Google Scholar 

  33. Dempsey EW, Wislocki GB (1955) An electron microscopic study of the blood brain barrier in the rat, employing silver nitrate as a vital stain. J Biophys Biochem Cytol 1:245–256

    Article  CAS  PubMed  Google Scholar 

  34. Denton DA, McKinley MJ, Weisinger RS (1996) Hypothalamic integration of body fluid regulation. PNAS 93:7397–7404

    Article  CAS  PubMed  Google Scholar 

  35. Duvernoy H, Koritke JG (1964) Contribution a l’etude de l’angioarchitectonie des organes circumventricularies. Arch Biol 75:849–904

    Google Scholar 

  36. Duvernoy H, Koritke JG (1969) Concerning the relationships of the circumventricular organs and their vessels with the cavity of he ventricles. In: Sterba G (ed) Zirkumventrikulare Organe und Liquor. VEB Gustav Fischer Verlag, Jena., pp 113–115

    Google Scholar 

  37. Duvernoy HM, Risold P-Y (2007) The circumventricular organs: an atlas of comparative anatomy and vascularization. Brain Res Rev 56:119–147

    Article  PubMed  Google Scholar 

  38. Ehrlich P (1885) Das Sauerstoff-Bedurfnis des Organismus: eine Farbenanalytische studie. Hirschwald, Berlin

    Google Scholar 

  39. Ehrlich P (1956) Über die methylenblaureaktion der lebenden Nervensubstans. In: Himmelweit F (ed) The Collected Papers of Paul Elrich. Pergamon Press, London, pp 500–508 (reprinted from Deutche Medizinische Wochen Schrift 1886)

    Google Scholar 

  40. Eikelenboom P, Bate C, Van Gool WA et al (2002) Neuroinflammation in Alzheimer’s disease and prion disease. Glia 40:232–239

    Article  CAS  PubMed  Google Scholar 

  41. Elmquist JK, Breder CD, Sherin JE et al (1997) Intravenous lipopolysaccharide induce cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages. J Comp Neurol 381:119–129

    Article  CAS  PubMed  Google Scholar 

  42. Ferguson AV, Bains JS (1996) Electrophysiology of the circumventricular organs. Front Neuroendocrinol 17:440–475

    Article  CAS  PubMed  Google Scholar 

  43. Ferguson AV, Kasting NW (1986) Electrical stimulation in the subfornical organ increases plasma vasopressin concentrations in the conscious rat. Am J Physiol 251:425–428

    Google Scholar 

  44. Ferguson AV, Kasting NW (1987) Activation of subfornical organ efferents stimulates oxytocin concentrations in the rat. Regul Pept 18:93–100

    Article  CAS  PubMed  Google Scholar 

  45. Ferguson AV, Kasting NW (1988) Angiotensin acts at the subfornical organ to increase plasma oxytocin concentrations in the rat. Regul Pept 23:343–352

    Article  CAS  PubMed  Google Scholar 

  46. Fitts DA, Masson DB (1990) Preoptic angiotensin and salt appetite. Behav Neurosci 104:643–650

    Article  CAS  PubMed  Google Scholar 

  47. Fry M, Ferguson AV (2007) The sensory circumventricular organs: brain targets for circulating signals controlling ingestive behaviour. Physiol Behav 91:413–423

    Article  CAS  PubMed  Google Scholar 

  48. Galea I, Bechmann I, Perry VH (2007) What is immune privilege (not)? Trends Immunol 28:12–18

    Article  CAS  PubMed  Google Scholar 

  49. Ganong WF (2000) Circumventricular organs: definition and role in the regulation of endocrine and autonomic function. Clin Exp Pharmacol Physiol 27:422–427

    Article  CAS  PubMed  Google Scholar 

  50. Gao H-M, Hong J-S (2008) Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol 29:357–365

    Article  CAS  PubMed  Google Scholar 

  51. Gayrard V, Picard-Hagen N, Grino M et al (2000) Major hypercorticism is an endocrine feature of ewes with naturally occurring scrapie. Endocrinology 141:988–994

    Article  CAS  PubMed  Google Scholar 

  52. Giles ME, Fernley RT, Nakamura Y et al (1999) Characterization of a specific antibody to the rat angiotensin II AT1 receptor. J Histochem Cytochem 47:507–516

    CAS  PubMed  Google Scholar 

  53. Glover DG, Pollard BJ, González L, Sisó S, Kennedy D, Jeffrey M (2007) A non-invasive screen for infectivity in transmissible spongiform encephalopathies. Gut 56:1329–1330

    Article  CAS  PubMed  Google Scholar 

  54. Goldmann EE (1909) Die äussere and innere Sekretion des gesunden und kranken Organismus im Lichte der “vitalen Färbung”. Beitr Klin Chir 64:192–265

    Google Scholar 

  55. González L, Martin S, Hawkins SA, Goldmann W, Jeffrey M, Sisó S (2010) Pathogenesis of natural goat scrapie: modulation by host PRNP genotype and effect of co-existent conditions. Vet Res 41:48

    Article  PubMed  Google Scholar 

  56. Goren O, Adorján I, Kálmán M (2006) Heterogenous occurrence of aquaporin-4 in the ependyma and in the circumventricular organs in rat and chicken. Anat Embryol 211:155–172

    Article  CAS  PubMed  Google Scholar 

  57. Gross PM (1987) Circumventricular organs and body fluids, Chaps. 1, 7, 8 in vol I, and Chap. 1 of vol II, and III. CRC Press, Boca Raton

    Google Scholar 

  58. Gross PM (1991) Morphology and physiology of capillary systems in subregions of the subfornical organ and area postrema. Can J Physiol Pharmacol 69:1010–1025

    CAS  PubMed  Google Scholar 

  59. Gross PM, Weindl A (1987) Peering through the windows of the brain. J Cereb Blood Flow Metabol 7:663–672

    CAS  Google Scholar 

  60. Gu GB, Simerly RB (1997) Projections of the sexually dimorphic anteroventral periventricular nucleus in the female rat. J Comp Neurol 384:142–164

    Article  CAS  PubMed  Google Scholar 

  61. Guan JL, Wang QP, Shioda S (2000) Observation of the ultrastructure and synaptic relationships of angiotensin II-like immunoreactive neurons in the rat area postrema. Synapse 38:231–237

    Article  CAS  PubMed  Google Scholar 

  62. Gutman MB, Ciriello J, Mogenson GJ (1988) Effects of plasma angiotensin II and hypernatremia on subfornical organ neurons. Am J Physiol 254:R746–R754

    CAS  PubMed  Google Scholar 

  63. Guyenet PG (2006) The sympathetic control of blood pressure. Nat Rev Neurosci 7:335–346

    Article  CAS  PubMed  Google Scholar 

  64. Haywood JR, Fink GD, Buggy J, Boutelle S, Johnson AK, Brody MJ (1983) Prevention of two-kidney, one clip renal hypertension in rat by ablation of AV3V tissue. Am J Physiol 245:683–689

    Google Scholar 

  65. Hofer H (1958) Zur Morphologie der circumventrikulären Organe des Zwischenhirns der Säugetiere. Verhandl Deut Zool Ges 8:202–251

    Google Scholar 

  66. Holmes MC, Catt KJ, Aguilera G (1987) Involvement of vasopressin in the down-regulation of pituitary corticotropin-releasing factor receptors after adrenolectomy. Endocrinology 121:2093–2098

    Article  CAS  PubMed  Google Scholar 

  67. Honda K, Negoro H, Higuchi T, Tadokoro Y (1987) Activation of neurosecretory cells by osmotic stimulation of anteroventral third ventricle. Am J Physiol 252:R1039–R1045

    CAS  PubMed  Google Scholar 

  68. Irwin MR, Miller AH (2007) Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun 21:374–383

    Article  CAS  PubMed  Google Scholar 

  69. Johnston AK, Gross PM (1993) Sensory circumventricular organs and brain homeostatic pathways. FASEB J 7:678–686

    Google Scholar 

  70. Jones CR, Hiley CR, Pelton JT, Mohr M (1989) Autoradiographic visualization of the binding sites for [125I] endothelin in rat and human brain. Neurosci Lett 97:276–279

    Article  CAS  PubMed  Google Scholar 

  71. Kalia M, Mesulam MM (1980) Brain stem projections of sensory and motor components of the vagus complex in the cat: I. The cervical vagus and nodose ganglion. J Comp Neurol 193:435–465

    Article  CAS  PubMed  Google Scholar 

  72. Kalia M, Sullivan JM (1982) Brainstem projections of sensory and motor components of the vagus nerve in the rat. J Comp Neurol 211:248–265

    Article  CAS  PubMed  Google Scholar 

  73. Katsuura G, Gottschall PE, Dahl RR, Arimura A (1988) Adrenocorticotropin release induce by intracerebroventricular injection of recombinant human interleukin-1 in rats: possible involvement of prostaglandin. Endocrinology 122:1773–1779

    Article  CAS  PubMed  Google Scholar 

  74. Kawano H, Masuko S (2001) Tyrosine hydroxylase-immunoreactive projections from the caudal ventrolateral medulla to the subfornical organ in the rat. Brain Res 903:154–161

    Article  CAS  PubMed  Google Scholar 

  75. Konsman JP, Kelley K, Dantzer R (1991) Temporal and spatial relationships between lipopolysaccharide-induced expression of Fos, interleukin-1β and inducible nitric oxide synthase in rat brain. Neuroscience 89:535–548

    Article  Google Scholar 

  76. Krisch B, Leonhardt H, Oksche A (1987) Compartments in the organum vasculosum laminae terminalis of the rat and their delineation against the outer cerebrospinal fluid-containing space. Cell Tissue Res 250:331–347

    Article  CAS  PubMed  Google Scholar 

  77. Kristensson K, Nygård M, Bertini G, Bentivoglio M (2010) African trypanosome infections of the nervous system: parasite entry and effects on sleep and synaptic functions. Prog Neurobiol 91:152–171

    Article  CAS  PubMed  Google Scholar 

  78. Krout KE, Kawano J, Mettenleiter TC, Loewy AD (2001) CNS inputs to the suprachiasmatic nucleus of the rat. Neuroscience 110:73–92

    Article  Google Scholar 

  79. Kubo S, Inui T, Yamazato K (2004) Visualisation of the circumventricular organs by fluorescence endoscopy. J Neurol Neurosurg Psychiatry 75:180

    CAS  PubMed  Google Scholar 

  80. Kushner I (1982) The phenomenon of the acute phase response. Ann NY Acad Sci 389:39–48

    Article  CAS  PubMed  Google Scholar 

  81. Li NC, Lee A, Whitmer RA, Kivipelto M, Lawler E, Kazis LE, Wolozin B (2010) Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 340:b5465. doi:10.1136/bmj.b5465

    Article  PubMed  Google Scholar 

  82. Lie DC, Song H, Colamarino SA, Ming GL, Gage FH (2004) Neurogenesis in the adult brain: new strategies for central nervous system diseases. Annu Rev Pharmacol Toxicol 44:399–421

    Article  CAS  PubMed  Google Scholar 

  83. Lind RW (1987) Neural connections. In: Gross PM (ed) Circumventricular organs and body fluids, vol I. CRC Press, Boca Raton, pp 27–42

    Google Scholar 

  84. Lind RW, Van Hoesen GW, Johnson AK (1982) An HRP study of the connections of the subfornical organ of the rat. J Comp Neurol 210:265–277

    Article  CAS  PubMed  Google Scholar 

  85. Lugaresi E, Provini F, Montagna P (2004) The neuroanatomy of sleep. Considerations on the role of the thalamus in sleep and a proposal for a caudorostral organization. Eur J Anat 8:85–94

    Google Scholar 

  86. Mangiapane ML, Brody MJ (1987) Vasoconstrictor and vasodilator sites within anteroventral third ventricle region. Am J Physiol 253:R827–R831

    CAS  PubMed  Google Scholar 

  87. Maolood N, Meister B (2009) Protein components of the blood–brain barrier (BBB) in the brainstem area postrema-nucleus tractus solitarius region. J Chem Neuroanat 37:182–195

    Article  CAS  PubMed  Google Scholar 

  88. McBride PA, Schulz-Schaeffer WJ, Donaldson M et al (2001) Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves. J Virol 75:9320–9327

    Article  CAS  PubMed  Google Scholar 

  89. McKinley MJ, Bicknell RJ, Hards D et al (1992) Efferent neural pathways of the lamina terminalis subserving osmoregulation. Prog Brain Res 91:395–402

    Article  CAS  PubMed  Google Scholar 

  90. McKinley MJ, Congiu M, Miselis RR, Oldfield BJ, Pennington G (1988) The lamina terminalis and osmotically stimulated vasopressin secretion. In: Yoshida S, Share L (eds) Recent progress in pituitary hormones. Excerpta Medica, Amsterdam, pp 117–124

    Google Scholar 

  91. McKinley MJ, McAllen RM, Davern P et al (2003) The sensory circumventricular organs of the mammalian brain. In: Advances in anatomy embryology and cell biology, vol 172, 1st edn. Springer, Berlin, Heidelberg

  92. Mészáros T, Leranth C, Palkovits M, Hazas J (1969) Secretory and esterase activity of the circumventricular organs with special reference to the infundibular ependyma. In: Sterba G (ed) Zirkumventrikulare Organe und Liquor. VEB Gustav Fischer Verlag, Jena, pp 131–134

    Google Scholar 

  93. Mignone JL, Kukekov V, Chiang AS, Steindler D, Enikolopov G (2004) Neural stem and progenitor cells in nestin-GFP transgenic mice. J Comp Neurol 469:311–324

    Article  CAS  PubMed  Google Scholar 

  94. Miselis RR (1981) The efferent projections of the subfornical organ of the rat: a circumventricular organ within a neural network subserving water balance. Brain Res 230:1–23

    Article  CAS  PubMed  Google Scholar 

  95. Miselis RR, Shapiro RE, Hand PJ (1979) Subfornical organ efferents to neural systems for control of body water. Science 205:1022–1102

    Article  CAS  PubMed  Google Scholar 

  96. Miselis RR, Weiss ML, Shapiro RE (1987) Modulation of the visceral neuraxis. In: Gross PM (ed) Circumventricular organs and body fluids, vol III. CRC Press, Boca Raton, pp 143–162

    Google Scholar 

  97. Morest DK (1960) A study of the structure of the area postrema with Golgi methods. Am J Anat 107:291–303

    Article  CAS  PubMed  Google Scholar 

  98. Mullier A, Bouret SG, Prevot V, Dehouck B (2010) Differential distribution of tight junction proteins suggests a role for tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain. J Comp Neurol 518:943–962

    Article  CAS  PubMed  Google Scholar 

  99. Oldfield BJ, Badoe E, Hards DK, McKinley MJ (1994) Fos production in retrogradely labelled neurons of the lamina terminalis following intravenous infusion of either hypertonic saline or angiotensin II. Neuroscience 60:255–262

    Article  CAS  PubMed  Google Scholar 

  100. Oldfield BJ, Hards DK, McKinley MJ (1991) Projections from the subfornical organ to the supraoptic nucleus in the rat: ultrastructural identification of an interposed synapse in the median preoptic nucleus using a combination of neural tracers. Brain Res 558:13–19

    Article  CAS  PubMed  Google Scholar 

  101. Oldfield BJ, Miselis RR, McKinley MJ (1991) Median preoptic nucleus projections to vasopressin-containing neurons of the supraoptic nucleus in sheep—a light and electron microscope study. Brain Res 542:193–200

    Article  CAS  PubMed  Google Scholar 

  102. Pan W, Kastin AJ (2007) Adipokines and the blood–brain barrier. Peptides 28:1317–1330

    Article  CAS  PubMed  Google Scholar 

  103. Parry HB (1962) Scrapie: a transmissible and hereditary disease of sheep. Heredity 17:75–105

    Article  CAS  PubMed  Google Scholar 

  104. Parry HB, Livett BG (1973) A new hypothalamic pathway to the median eminence containing neurophysin and its hypertrophy in sheep with natural scrapie. Nature 242:63–65

    Article  CAS  PubMed  Google Scholar 

  105. Parry HB, Livett BG (1976) Neurophysin in the brain and pituitary gland of normal and scrapie-affected sheep—I. Its localization in the hypothalamus and neurohypophysis with particular reference to a new hypothalamic neurosecretory pathway to the median eminence. Neuroscience 1:275–299

    Article  CAS  PubMed  Google Scholar 

  106. Pecchi E, Dallaporta M, Charrier C et al (2007) Glial fibrillary acidic protein (GFAP)-positive radial-like cells are present in the vicinity of proliferative progenitors in the nucleus tractus solitarius of adult rat. J Comp Neurol 501:353–368

    Article  CAS  PubMed  Google Scholar 

  107. Peress NS, Perillo E, Fenstermacher JD (1989) Circumventricular organs in chronic serum sickness: a model for cerebral lupus. Biol Psychiatry 26:397–407

    Article  CAS  PubMed  Google Scholar 

  108. Petrov T, Howarth AG, Krukoff TL, Stevenson BR (1994) Distribution of the tight junction-associated protein ZO-1 in circumventricular organs of the CNS. Mol Brain Res 21:235–246

    Article  CAS  PubMed  Google Scholar 

  109. Phillips MI, Camacho A (1987) Neural connections of the organum vasculosum of the lamina terminalis. In: Gross PM (ed) Circumventricular organs and body fluids, vol I. CRC Press, Boca Raton., pp 157–169

    Google Scholar 

  110. Picard-Hagen N, Gayrard V, Alvinerie M et al (2000) Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes. J Endocrinol 165:527–532

    Article  CAS  PubMed  Google Scholar 

  111. Price CJ, Hoyda TD, Ferguson AV (2008) The area postrema: a brain monitor and integrator of systemic autonomic state. Neuroscientist 14:182–194

    Article  PubMed  Google Scholar 

  112. Preuss MA, Faber ML, Tan GS et al (2009) Intravenous inoculation of a bat-associated rabies virus causes lethal encephalopathy in mice through invasion of the brain via neurosecretory hypothalamic fibers. PLoS Pathog 5(6):e1000485

    Article  PubMed  CAS  Google Scholar 

  113. Provini F, Cortelli P, Montagna P, Gambetti P, Lugaresi E (2008) Fatal insomnia and agrypnia excitata: sleep and the limbic system. Rev Neurol 164:692–700

    Article  CAS  PubMed  Google Scholar 

  114. Putnam TJ (1922) The intercolumnar tubercle: an undescribed area in the anterior wall of the third ventricle. Bull J Hopkins Hosp 33:181

    Google Scholar 

  115. Richard D, Bourque CW (1995) Synaptic control of rat supraoptic neurons during osmotic stimulation of the organum vasculosum lamina terminalis in vitro. J Physiol 489:567–577

    CAS  PubMed  Google Scholar 

  116. Roth J, Harré EM, Rummel C, Gerstberger R, Hübschle T (2004) Signaling the brain in systemic inflammation: role of sensory circumventricular organs. Front Biosci 9:290–300

    Article  CAS  PubMed  Google Scholar 

  117. Sánchez-Álavez M, Criado JR et al (2008) Hypothalamic-pituitary-adrenal axis disregulation in PrPC-null mice. Neuroreport 19:1473–1477

    Article  PubMed  CAS  Google Scholar 

  118. Scammell TE, Elmquist JK, Griffin JD, Saper CB (1996) Ventromedial preoptic prostaglandin E2 activates fever-producing autonomic pathways. J Neurosci 16:6246–6254

    CAS  PubMed  Google Scholar 

  119. Schelcher F, Picard-Hagen N, Laroute V et al (1999) Corticoid concentrations are increased in the plasma and urine of ewes with naturally occurring scrapie. Endocrinology 140:2422–2425

    Article  CAS  PubMed  Google Scholar 

  120. Schulz M, Engelhardt B (2005) The circumventricular organs participate in the immunopathogenesis of experimental autoimmune encephalomyelitis. Cerebrospinal Fluid Res 2:8

    Article  PubMed  CAS  Google Scholar 

  121. Schultzberg M, Ambatsis M, Samuelsson EB, Kristensson K, van Meirvenne N (1988) Spread of Trypanosoma brucei to the nervous sytem: early attack on circumventricular organs and sensory ganglia. J Neurosci Res 21:56–61

    Article  CAS  PubMed  Google Scholar 

  122. Schwendemann G (1973) Zur Ultrastruktur des Organon vasculosum laminae terminalis der ratte mit besonderer Berucksichtigung der Gefaße. In: Advances in anatomy, embryology and cell biology, vol 47. Springer, Berlin Heidelberg. pp 7–72

  123. Shapiro RE, Miselis RR (1985) The central connections of the area postrema of the rat. J Comp Neurol 234:344–364

    Article  CAS  PubMed  Google Scholar 

  124. Shaver SW, Pang JJ, Wainman DS, Wall KM, Gross PM (1992) Morphology and function of capillary networks in subregions of the rat tuber cinereum. Cell Tissue Res 267:437–448

    Article  CAS  PubMed  Google Scholar 

  125. Shaver SW, Pang JJ, Wall KM, Sposito NM, Gross PM (1991) Subregional topography of capillaries in the dorsal vagal complex of rats. I. Morphometric properties. J Comp Neurol 306:73–82

    Article  CAS  PubMed  Google Scholar 

  126. Shaver SW, Sposito NM, Gross PM (1990) Quantitative fine structure of capillaries in subregions of the rat subfornical organ. J Comp Neurol 294:145–152

    Article  CAS  PubMed  Google Scholar 

  127. Shekhar A, Keim SR (1997) The circumventricular organs form a potential neural pathway for lactate sensitivity: implications for panic disorder. J Neurosci 17:9726–9735

    CAS  PubMed  Google Scholar 

  128. Schröder R, Linke RP (1999) Cerebrovascular involvement in systemic AA and AL amyloidosis: a clear haematogenic pattern. Virchows Arch 434:551–560

    Article  PubMed  Google Scholar 

  129. Simpson JB (1981) The circumventricular organs and the central actions of angiotensin. Neuroendocrinology 32:248–256

    Article  CAS  PubMed  Google Scholar 

  130. Sisó S, Jeffrey M, González L (2009) Neuroinvasion in sheep transmissible spongiform encephalopathies: the role of the haematogenous route. Neuropathol Appl Neurobiol 35:232–246

    Article  PubMed  CAS  Google Scholar 

  131. Sisó S, Jeffrey M, González L (2010) Neuroinvasion in prion diseases: the roles of ascending neural infection and blood dissemination. Interdiscip Perspect Infect Dis 2010:747892. doi:10.1155/2010/747892

    PubMed  Google Scholar 

  132. Solano-Flores LP, Rosas-Arellano MP, Ciriello J (1997) Fos induction in central structures after afferent renal nerve stimulation. Brain Res 753:102–119

    Article  CAS  PubMed  Google Scholar 

  133. Song K, Allen AM, Paxinos G, Mendelsohn FA (1992) Mapping of angiotensin II receptor subtype heterogeneity in rat brain. J Comp Neurol 316:467–484

    Article  CAS  PubMed  Google Scholar 

  134. Spiegel EA (1918) Das ganglion psalterii. Anat Anz 51:454–462

    Google Scholar 

  135. Summy-Long JY, Kadekaro M (2001) Circumventricular organs: gateways to the brain. role of circumventricular organs (CVO) in neuroendocrine responses: interactions of CVO and the magnocellular neuroendocrine system in different reproductive states. Clin Exp Pharmacol Physiol 28:590–601

    Article  CAS  PubMed  Google Scholar 

  136. Sunn N, McKinley MJ, Oldfield BJ (2001) Identification of efferent neural pathways from the lamina terminalis activated by blood-borne relaxin. J Neuroendocrinol 13:432–437

    Article  CAS  PubMed  Google Scholar 

  137. Steinman L (2004) Elaborate interactions between the immune and nervous systems. Nat Immunol 5:575–581

    Article  CAS  PubMed  Google Scholar 

  138. Steinman L (2008) Nuanced roles of cytokines in three major human brain disorders. J Clin Invest 118:3557–3563

    Article  CAS  PubMed  Google Scholar 

  139. Swaab DF, Ai-Min B, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 4:141–194

    Article  CAS  PubMed  Google Scholar 

  140. Swanson LW, Lind RW (1986) Neural projections subserving the initiation of a specific motivated behavior in the rat: new projections from the subfornical organ. Brain Res 379:399–403

    Article  CAS  PubMed  Google Scholar 

  141. Tanaka J, Saito H, Kaba H (1987) Subfornical organ and hypothalamic paraventricular nucleus connections with median preoptic nucleus neurons: an electrophysiological study in the rat. Exp Brain Res 68:579–585

    CAS  PubMed  Google Scholar 

  142. Turrin NP, Rivest S (2004) Unraveling the molecular details involved in the intimate link between the immune and neuroendocrine systems. Exp Biol Med (Maywood) 229:996–1006

    CAS  Google Scholar 

  143. Ulrich-Lai YM, Herman JP (2009) Neural regulation of endocrine and autonomic stress responses. Nat Rev 10:397–409

    Article  CAS  Google Scholar 

  144. Undesser KP, Hasser E, Haywood JR, Johnson AK, Bishop VS (1985) Interactions of vasopressin with the area postrema in arterial baroreflex function in conscious rabbits. Circ Res 56:410–417

    CAS  PubMed  Google Scholar 

  145. Uschakov A, McAllen RM, Oldfield BJ, McKinley MJ (2001) Efferent projections of subpopulations of neurons in the lamina terminalis. Abstr Soc Neurosci 27:733–738

    Google Scholar 

  146. van Breemen VL, Clemente CD (1955) Silver deposition in the central nervous system and the hematoencephalic barrier studied with the electron microscope. J Biophys Biochem Cytol 1:161–166

    Article  Google Scholar 

  147. Van Dam A-M, Brouns M, Man-A-Hing W, Berkenbosch F (1993) Immunocytochemical detection of prostaglandin E2 in microvasculature of rat brain after administration of bacterial endotoxin. Brain Res 613:331–336

    Article  CAS  PubMed  Google Scholar 

  148. van der Kooy D, Koda LY (1983) Organization of the projections of a circumventricular organ: the area postrema in the rat. J Comp Neurol 219:328–338

    Article  PubMed  Google Scholar 

  149. van Keulen LJM, Vromans MEW, van Zijderveld FG (2002) Early and late pathogenesis of natural scrapie infection in sheep. APMIS 110:23–32

    Article  PubMed  Google Scholar 

  150. Viguié C, Chilliard Y, Gayrard V et al (2004) Alterations of somatotropic function in prion disease in sheep. J Endocr 183:427–435

    Article  PubMed  CAS  Google Scholar 

  151. Vivas L, Chiaraviglio E, Carrer HF (1990) Rat organum vasculosum laminae terminalis I vitro-responses to changes in sodium concentration. Brain Res 519:294–300

    Article  CAS  PubMed  Google Scholar 

  152. Watkins AD (1994) Hierarchical cortical control of neuroimmunomodulatory pathways. Neuropathol Appl Neurobiol 20:423–431

    Article  CAS  PubMed  Google Scholar 

  153. Wilson AJ, Carati CJ, Gannon BJ, Haberberger R, Chataway TK (2010) Aquaporin-1 in blood vessels of rat circumventricular organs. Cell Tissue Res 340:159–168

    Article  CAS  PubMed  Google Scholar 

  154. Wislocki GB, Leduc EH (1952) Vital staining of the hematoencephalic barrier by silver nitrate and trypan blue, and cytological comparison of the neurohypophysis, pineal body, area postrema, intercolumnar tubercle and supraoptic crest. J Comp Neurol 96:371–414

    Article  CAS  PubMed  Google Scholar 

  155. Wislocki GB, Putnam TJ (1924) Further observations on the anatomy and physiology of the areae postremae. Anat Rec 27:151–156

    Article  Google Scholar 

  156. Wyss-Coray T (2006) Inflammation in Alzheimer disease: driving force, bystander or beneficial response. Nat Med 12:1005–1015

    CAS  PubMed  Google Scholar 

  157. Wyss-Coray T, Mucke L (2002) Inflammation in neurodegenerative disease: a double-edged sword. Neuron 35:419–432

    Article  CAS  PubMed  Google Scholar 

  158. Ye X, Carp RI, Yu Y, Kozielski R, Kozlowski P (1994) Effect of infection with the 139H scrapie strain on the number, area and/or location of hypothalamic CRF- and VP-immunostained neurons. Acta Neuropathol 88:44–54

    Article  CAS  PubMed  Google Scholar 

  159. Zoukos Y, Leonard JP, Thomaides T, Thompson AJ, Cuzner ML (1992) β-Adrenergic receptor density and function of peripheral blood mononuclear cells are increased in multiple sclerosis: a regulatory role for cortisol and interleukin-1. Ann Neurol 31:657–662

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors greatly appreciate the help provided by Dr. Gillian McGovern in adapting and reproducing Figs. 3, 4 and 6. The authors also thank Dr. James Hope for critically reading the manuscript.

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Sisó, S., Jeffrey, M. & González, L. Sensory circumventricular organs in health and disease. Acta Neuropathol 120, 689–705 (2010). https://doi.org/10.1007/s00401-010-0743-5

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