Skip to main content

Advertisement

Log in

Different vascular permeability between the sensory and secretory circumventricular organs of adult mouse brain

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The blood-brain barrier (BBB) prevents free access of circulating molecules to the brain and maintains a specialized brain environment to protect the brain from blood-derived bioactive and toxic molecules; however, the circumventricular organs (CVOs) have fenestrated vasculature. The fenestrated vasculature in the sensory CVOs, including the organum vasculosum of lamina terminalis (OVLT), subfornical organ (SFO) and area postrema (AP), allows neurons and astrocytes to sense a variety of plasma molecules and convey their information into other brain regions and the vasculature in the secretory CVOs, including median eminence (ME) and neurohypophysis (NH), permits neuronal terminals to secrete many peptides into the blood stream. The present study showed that vascular permeability of low-molecular-mass tracers such as fluorescein isothiocyanate (FITC) and Evans Blue was higher in the secretory CVOs and kidney as compared with that in the sensory CVOs. On the other hand, vascular permeability of high-molecular-mass tracers such as FITC-labeled bovine serum albumin and Dextran 70,000 was lower in the CVOs as compared with that in the kidney. Prominent vascular permeability of low- and high-molecular-mass tracers was also observed in the arcuate nucleus. These data demonstrate that vascular permeability for low-molecular-mass molecules is higher in the secretory CVOs as compared with that in the sensory CVOs, possibly for large secretion of peptides to the blood stream. Moreover, vascular permeability for high-molecular-mass tracers in the CVOs is smaller than that of the kidney, indicating that the CVOs are not totally without a BBB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Arimura A (2000) Hypothalamic Hormones. In: Conn PM, Freeman ME (eds) Neuroendocrinology in physiology and medicine. Humana, New Jersey, p 43

    Google Scholar 

  • Betz AL, Goldstein GW (1978) polarity of the blood–brain barrier: neutral amino acid transport isolated brain capillaries. Science 202:225–227

    Article  PubMed  CAS  Google Scholar 

  • Broadwell RD, Brightman MW (1976) Entry of peroxidase into neurons of the central and peripheral nervous systems from extracerebral and cerebral blood. J Comp Neurol 166:257–283

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Chakravarty S, Herkenham M (2005) Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. J Neurosci 25:1788–1796

    Article  PubMed  CAS  Google Scholar 

  • Charron G, Laforest S, Gagnon C, Drolet G, Mouginot D (2002) Acute sodium deficit triggers plasticity of the brain angiotensin type 1 receptors. FASEB J 16:610–2

    PubMed  CAS  Google Scholar 

  • Ciofi P (2009) Brain-endocrine interactions: a microvascular route in the mediobasal hypothalamus. Endocrinology 150:5509–5519

    Article  PubMed  CAS  Google Scholar 

  • Ciura S, Bourque CW (2006) Transient receptor potential vanilloid 1 is required for intrinsic osmoreception in organum vasculosum lamina terminalis neurons and for normal thirst responses to systemic hyperosmolality. J Neurosci 26:9069–9075

    Article  PubMed  CAS  Google Scholar 

  • Crone C, Olesen SP (1982) Electrical resistance of brain microvascular endothelium. Brain Res 241:49–55

    Article  PubMed  CAS  Google Scholar 

  • Daneman R, Zho L, Kebede AA, Barres BA (2010) Pericytes are required for blood–brain barrier integrity during embryogenesis. Nature 468:562–566

    Article  PubMed  CAS  Google Scholar 

  • del Valle J, Camins A, Pallàs M, Vilaplana J, Pelegrí C (2008) A new method for determining blood–brain barrier integrity based on intracardiac perfusion of an Evans Blue-Hochst cocktail. J Neurosci Meth 174:42–49

    Article  Google Scholar 

  • Dellman HD (1987) The subfornical organ. In: Gross PM (ed) Fine structure. In circumventricyular organs and body fluids. CRC, Boca Raton, pp 4–25, Vol. I

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Dermietzel R (1975) Junctions in the central nervous system of the cat. Cell Tissue Res 64:45–62

    Google Scholar 

  • Engelhardt B (2003) Development of the blood–brain barrier. Cell Tissue Res 314:119–129

    Article  PubMed  CAS  Google Scholar 

  • Faouzi M, Leshan R, Björnholm M, Hennessey T, Jones J, Münzberg H (2007) Differential accessibility of circulating leptin to individual hypothalamic sites. Endocrinology 148:5414–23

    Article  PubMed  CAS  Google Scholar 

  • Faraci FM, Choi J, Baumbach GL, Mayhan WG, Heistad DD (1989) Microcirculation of the area postrema: permeability and vascular responses. Circ Res 65:417–425

    Article  PubMed  CAS  Google Scholar 

  • Fitzsimons JT (1998) Angiotensin, thirst, and sodium appetide. Physiol Rev 78:583–686

    PubMed  CAS  Google Scholar 

  • Fry M, Hoyda TD, Ferguson AV (2007) Making sense of it: role of the sensory circumventricular organs in feeding and regulation of energy homeostasis. Exp Biol Med 232:14–26

    CAS  Google Scholar 

  • Ganong WF (2000) Circumventricular organs: definition and role in the regulation of endocrine and autonomic function. Clin Exp Pharmacol Physiol 27:422–7

    Article  PubMed  CAS  Google Scholar 

  • Gross PM (1992) Circumventricular organ capillaries. Prog Brain Res 91:219–233

    Article  PubMed  CAS  Google Scholar 

  • Hallmann R, Horn N, Selg M, Wendler O, Pausch F, Sorokin LM (2005) Expression and function of laminins in the embryonic and mature vasculature. Physiol Rev 85:979–1000

    Article  PubMed  CAS  Google Scholar 

  • Harré EM, Roth J, Pehl U, Kueth M, Gerstberger R, Hübschle T (2002) Selected contribution: role of IL-6 in LPS-induced nuclear STAT3 translocation in sensory circumventricular organs during fever in rats. J Appl Physiol 92:2657–2666

    PubMed  Google Scholar 

  • Hawkins RA (2009) The blood–brain barrier and glutamate. Am J Clin Nutr 90:867–874S

    Article  Google Scholar 

  • Hawkins BT, Egleton RD (2006) Fluorescence imaging of blood–brain barrier disruption. J Neurosci Methods 151:262–7

    Article  PubMed  CAS  Google Scholar 

  • Hiyama T, Watanabe E, Okado K, Noda M (2004) The subfornical organ is the primary locus of sodium-level sensing by Na, sodium channels for the control of salt-intake behavior. J Neurosci 24:9276–9281

    Article  PubMed  CAS  Google Scholar 

  • Holmes KL, Lantz LM (2001) Protein labeling with fluorescent probes. Methods Cell Biol 63:185–204

    Article  PubMed  CAS  Google Scholar 

  • Hornby PJ (2001) Central neurocircuitry associated with emesis. Am J Med Suppl 8A:106S–112S

    Google Scholar 

  • Imamura Y, Morita S, Nakatani N, Okada K, Ueshima S, Matsuo O, Miyata S (2010) Tissue plasminogen activator and plasminogen are critical for osmotic homeostasis by regulating vasopressin secretion. J Neurosci Res 88:1995–2006

    PubMed  CAS  Google Scholar 

  • Krause EG, Melhorn SJ, Davis JF, Scott KA, Ma LY, de Kloet AD, Benoit SC, Woods SC, Sakai RR (2008) Angiotensin type 1 receptors in the subfornical organ mediate the drinking and hypothalamic-pituitary-adrenal response to systemic isoproterenol. Endocrinology 149:6416–24

    Article  PubMed  CAS  Google Scholar 

  • Krisch B, Leonhard H (1989) Relationship between leptomeningeal compartments and the neurohemal regions of circumventricular organs. Biomed Res 10:155–168

    Google Scholar 

  • Lam TK, Schwartz GJ, Rossetti L (2005) Hypothalamic sensing of fatty acids. Nat Neurosci 8:579–584

    Article  PubMed  CAS  Google Scholar 

  • Liedtke W, Friedman JM (2003) Abnormal osmotic regulation in trpv4-/- mice. Proc Natl Acad Sci USA 100:13698–13703

    Article  PubMed  CAS  Google Scholar 

  • Liedtke W, Choe Y, Marti-Renom MA, Bell AM, Denis CS, Sali A, Hudspeth AJ, Friedman JM, Heller S (2000) Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 100:13698–13703

    Google Scholar 

  • Malmgren LT, Olsson Y (1980) Differences between the peripheral and the central nervous system in permeability to sodium fluorescein. J Comp Neurol 191:103–117

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Marin-Padilla M (1985) Early vascularization of the embryonic cerebral cortex: golgi and electron microscopic studies. J Comp Neurol 241:237–249

    Article  PubMed  CAS  Google Scholar 

  • Michalski D, Grosch J, Pelz J, Schneider D, Weise C, Bauer U, Kacza J, Gärtner U, Hobohm C, Härtig W (2010) A novel quantification of blood–brain barrier damage and histochemical typing after embryonic stroke in rats. Brain Res 1359:186–200

    Article  PubMed  CAS  Google Scholar 

  • Miller AD, Leslie RA (1994) The area postrema and vomiting. Front Neuroendocrinol 15:301–20

    Article  PubMed  CAS  Google Scholar 

  • Miyata S, Hatton GI (2002) Activity-related, dynamic neuron-glial Interactions in the hypothalamo-neurohypophysial system. Microsc Res Tech 56:143–157

    Article  PubMed  CAS  Google Scholar 

  • Miyata S, Morita S (2011) A new method for visualization of endothelial cells and extravascular leakage in adult mouse brain using fluorescein isothiocyanate. J Neurosci Methods 202:9–16

    Article  PubMed  CAS  Google Scholar 

  • Miyata S, Takamatsu H, Maekawa S, Matsumoto N, Watanabe K, Kiyohara T, Hatton GI (2001) Plasticity of neurohypophysial terminals with increased hormonal release during dehydration: ultrastructural and biochemical analyses. J Comp Neurol 343:413–427

    Article  Google Scholar 

  • Morita S, Oohira A, Miyata S (2010) Activity-dependent remodeling of chondroitin sulfate proteoglycans extracellular matrix in the hypothalamo-neurohypophysial system. Neuroscientist 166:1068–1082

    CAS  Google Scholar 

  • Mujumdar RB, Ernst LA, Mujumdar SR, Waggoner AS (1989) Cyanine dye labeling reagents containing isothiocyanate groups. Cytometry 10:11–19

    Article  PubMed  CAS  Google Scholar 

  • 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 518:943–62

    Article  PubMed  CAS  Google Scholar 

  • Murabe Y, Nishida K, Sano Y (1981) Cells capable of uptake horseradish peroxidase in some circumventricular organs of the cat and rat. Cell Tissue Res 219:85–92

    Article  PubMed  CAS  Google Scholar 

  • Natah SS, Mouthate A, Pittman QJ, Sharkey KA (2005) Disruption of blood–brain barrier during TNBS colitis. Neurogastroenterol Motil 17:433–446

    Article  PubMed  CAS  Google Scholar 

  • Noda M (2006) The subfornical organ, a specialized sodium channel, and the sensing of sodium levels in the brain. Neuroscientist 12:80–91

    Article  PubMed  CAS  Google Scholar 

  • Norsted E, Gömüç B, Meister B (2008) Protein components of the blood–brain barrier (BBB) in the mediobasal hypothalamus. J Chem Neuroanat 36:107–121

    Article  PubMed  CAS  Google Scholar 

  • Peruzzo B, Pastor FE, Blazquez JL, Armat P, Rodriguez EM (2004) Polarized endocytosis and transcytosis in the hypothalamic tancytes of the rat. Cell Tissue Res 317:147–164

    Article  PubMed  CAS  Google Scholar 

  • Prevot V, Dehouck B, Poulain P, Beauvillain JC, Buée-Scherrer V, Bouret S (2007) Neuronal-glial-endothelial interactions and cell plascticity in the postnatal hypothalamus: implications for neuroendocrine control of reproduction. Psychoneuroendocrinology 32(Suppl 1):S46–51

    Article  PubMed  CAS  Google Scholar 

  • Pulman KJ, Fry WM, Cottrell GT, Ferguson AV (2006) The subfornical organ: a central target for circulating feeding signals. J Neurosci 26:2022–2030

    Article  PubMed  CAS  Google Scholar 

  • Quan N, Whiteside M, Kim L, Herkenham M (1997) Induction of inhibitory factor κBα mRNA in the central nervous system after peripheral lipopolysaccharide administration: an in situ hybridization histochemistry study in the rat. Proc Natl Acad Sci USA 94:10985–10990

    Article  PubMed  CAS  Google Scholar 

  • Reynolds DS, Morton AJ (1998) Changes in blood–brain barrier permeability following neurotoxic lesions of rat brain can be visualized with trypan blue. J Neurosci Methods 79:115–121

    Article  PubMed  CAS  Google Scholar 

  • Rodríguez EM, Rodríguez S, Hein S (1998) The subcommissural organ. Microsc Res Tech 41:98–123

    Article  PubMed  Google Scholar 

  • Rodríguez EM, Blázquez JL, Guerra M (2010) The design of barriers in the hypothalamus allows the median eminence and the arcuate nucleus to enjoy private milieus: the former opens to the portal blood and the latter to the cerebrospinal fluid. Peptides 31:757–76

    Article  PubMed  Google Scholar 

  • Rummel C, Hübschle T, Gerstberger R, Roth J (2004) Nuclear translocation of the transcription factor STAT3 in the guinea pig brain during systemic or localized inflammation. J Physiol 557:671–687

    Article  PubMed  CAS  Google Scholar 

  • Schiller AA, Schayer RW, Hess EL (1953) Fluorescein-conjugated bovine albumin; Physical and biological properties. J Gen Physiol 36:489–506

    Article  PubMed  CAS  Google Scholar 

  • Shaver SW, Sposito NM, Gross PM (1990) Quantitative fine structure of capillaries in subregions of the rat subfornical organ. J Comp Neurol 294:145–1152

    Article  PubMed  CAS  Google Scholar 

  • Shekhar A, Kleim SR (1997) The circumventricular organs form a potential neural pathway for lactate sensitivity: implications for panic disorder. J Neurosci 17:9726–35

    PubMed  CAS  Google Scholar 

  • Shimizu H, Watanabe E, Hiyama TY, Nagakura A, Fujikawa A, Okada H, Yanagawa Y, Obata K, Noda M (2007) Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing. Neuron 54:59–72

    Article  PubMed  CAS  Google Scholar 

  • Sisó S, Jeffrey M, González L (2010) Sensory circumventricular organs in health and disease. Acta Neuropathol 120:689–705

    Article  PubMed  Google Scholar 

  • Strazielle N, Ghersi-Egea JF (2000) Choroid plexus in the central nervous system: biology and physiopathology. J Neuropathol Exp Neurol 59:561–574

    PubMed  CAS  Google Scholar 

  • Szallasi A, Cruz F, Geppetti P (2006) TRPV1: a therapeutic target for novel analgesic drugs? Trends Mol Med 12:545–54

    Article  PubMed  CAS  Google Scholar 

  • Tervo T, Joo F, Palkama A, Salminen L (1979) Penetration barrier to sodium fluorescein and fluoscein-labeled Dextrans of various molecular sizes in brain capillaries. Experimentia 35:252–254

    Article  CAS  Google Scholar 

  • Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple ain-producing stimuli. Neuron 21:531–43

    Article  PubMed  CAS  Google Scholar 

  • Wang Q-P, Guan J-L, Pan W, Kastin A, Shioda S (2008) A diffusion barrier between the area postrema and nucleus tractus solitarius. Neurochem Res 33:2035–2043

    Article  PubMed  CAS  Google Scholar 

  • Watanabe E, Fujikawa A, Matsunaga H, Yasoshima Y, Sako N, Yamamoto T, Saegusa C, Noda M (2000) Nav2/NaG channel is involved in control of salt-intake behavior in the CNS. J Neurosci 20:7743–51

    PubMed  CAS  Google Scholar 

  • Watanabe E, Hiyama TY, Shimizu H, Kodama R, Hayashi N, Miyata S, Yanagawa Y, Obata K, Noda M (2006) Sodium-level-sensitive sodium channel Na(x) is expressed in glial laminate processes in the sensory circumventricular organs. Am J Physiol 290:R568–76

    CAS  Google Scholar 

  • Willis CL, Garwood CJ, Ray DE (2007) A size selective vascular barrier in the rat area postrema formed by perivascular macrophages and the extracellular matrix. Neuroscientist 150:498–509

    CAS  Google Scholar 

Download references

Acknowledgment

The hybridoma of anti-CD31 (2H8) antibody developed by Drs. Steven Bogen was obtained from the DSHB developed under the auspices of the NICHD respectively and maintained by The University of Iowa, Iowa City, IA 52242. This work was supported in part by Scientific Research Grants from the Japan Society for the Promotion of Science (no.21500323 to S. Miyata) and Salt Science Research Foundation (no. 1137 to S. Miyata). Shoko Morita was supported by a Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists (no. 23·8513).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Seiji Miyata.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(JPEG 106 kb)

High resolution image (TIFF 2968 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morita, S., Miyata, S. Different vascular permeability between the sensory and secretory circumventricular organs of adult mouse brain. Cell Tissue Res 349, 589–603 (2012). https://doi.org/10.1007/s00441-012-1421-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-012-1421-9

Keywords

Navigation