Abstract
The blood-brain barrier (BBB) is the highly specialized and selective crossing area between blood and brain, essential for brain homeostasis and functioning, formed by the endothelial cells of the cerebral microvasculature in a rich and intimate cooperation with the neighboring cells and local signaling factors from both the brain and blood sides. Its distribution throughout the brain is following the brain cytoarchitectonic patterns, each capillary serving the adjacent neurons in a privileged neurovascular interplay that ultimately responds to the manifestation of brain functions, scaled from the cellular to the system level. At the edge of our understanding, cognition stands for what makes us humans and needs the cooperation of the entire body functioning to assist homeostatic favorable conditions for its manifestation. The cerebral endothelial system is operating at this interfacing point, modulating its own phenotype in accordance with various conditions to which the organism and brain are exposed, responding with changes in its permeability and signaling processes. In this chapter we will briefly describe the multicellular assembly of the neurovascular unit from which the BBB emerges, and its contribution to the brain homeostasis by dynamic neurovascular and neurometabolic coupling processes. Further, we will refer to the principal morphologic and functional features of the BBB from which its specific properties arise, making it not just a physical selective barrier, but also a metabolic, neuroimmune and endocrine interface. We will touch on the physiological implications of BBB and neurovascular coupling on high brain functions and cognition, in normal or disease-associated conditions.
Similar content being viewed by others
References
Aänismaa P, Gatlik-Landwojtowicz E, Seelig A (2008) P-glycoprotein senses its substrates and the lateral membrane packing density: consequences for the catalytic cycle. Biochemistry 47(38):10197–10207
Abbott NJ (2002) Astrocyte–endothelial interactions and blood–brain barrier permeability. J Anat 200(6):629–638. doi:10.1046/j.1469-7580.2002.00064.x
Abbott NJ (2004) Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem Int 45:545–552
Abbott NJ (2013) Blood–brain barrier structure and function and the challenges for CNS drug delivery. J Inherit Metab Dis 36:437. doi:10.1007/s10545-013-9608-0
Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci 7:41–53. doi:10.1038/nrn1824
Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ (2010) Structure and function of the blood–brain barrier. Neurobiol Dis 37:13–25
Akgoren N, Lauritzen M (1999) Functional recruitment of red blood cells to rat brain microcirculation accompanying increased neuronal activity in cerebellar cortex. Neuroreport 10:3257–3263
Amiry-Moghaddam M, Ottersen OP (2003) The molecular basis of water transport in the brain. Nat Rev Neurosci 4:991–1001
Andras IE, Toborek M (2016) Extracellular vesicles of the blood-brain barrier. Tissue Barriers 4(1):e1131804
Ardestani A, Shen W, Darvas F, Toga AW, Fuster JM (2016) Modulation of frontoparietal neurovascular dynamics in working memory. J Cogn Neurosci 28(3):379–401
Armulik A, Genové G, Mäe M et al (2010) Pericytes regulate the blood-brain barrier. Nature 468(7323):557–561
Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA (2010) Glial and neuronal control of brain blood flow. Nature 468:232–243
Attwell D, Mishra A, Hall CN, O’Farrell FM, Dalkara T (2015) What is a pericyte? J Cereb Blood Flow Metab 36(2):451–455
Banks WA (2008) The blood-brain barrier: connecting the gut and the brain. Regular Pept 149(1–3):11–14. doi:10.1016/j.regpep.2007.08.027
Banks WA (2012a) Role of the blood–brain barrier in the evolution of feeding and cognition. Issue: the brain and obesity. Ann NY Acad Sci 1264(2012):13–19. doi:10.1111/j.1749-6632.2012.06568.x
Banks WA (2012b) Brain meets body: the blood-brain barrier as an endocrine interface. Endocrinology 153(9):4111–4119. doi:10.1210/en.2012-1435
Banks WA (2004) The source of cerebral insulin. Eur J Pharmacol 490(1–3):5–12. ISSN 0014-2999, http://dx.doi.org/10.1016/j.ejphar.2004.02.040
Bar T (1980) The vascular system of the cerebral cortex. Springer, Berlin. doi:10.1007/978-3-642-67432-7
Barros LF (2013) Metabolic signaling by lactate in the brain. Trends Neurosci 36(7):396–404
Bartanusz V, Jezova D, Alajajian B, Digicaylioglu M (2011) The blood–spinal cord barrier: morphology and clinical implications. Ann Neurol 70:194–206. doi:10.1002/ana.22421
Bechter K, Reiber H, Herzog S, Fuchs D, Tumani H, Maxeiner HG (2010) Cerebrospinal fluid analysis in affective and schizophrenic spectrum disorders: identification of subgroups with immune responses and blood-CSF barrier dysfunction. J Psychiatr Res 44(5):321–330
Bleck TP, Smith MC, Pierre-louis SJ, Jares JJ, Murray J, Hansen CA (1993) Neurologic complications of critical medical illnesses. Crit Care Med 21(1):98–103
Boado RJ, Pardridge WM (1993) Glucose deprivation causes posttranscriptional enhancement of brain capillary endothelial glucose transporter gene expression via GLUT1 mRNA stabilization. J Neurochem 60:2290–2296. doi:10.1111/j.1471-4159.1993.tb03516.x
Boado RJ, Pardridge WM (2002) Glucose deprivation and hypoxia increase the expression of the GLUT1 glucose transporter via a specific mRNA cis-acting regulatory element. J Neurochem 80:552–554. doi:10.1046/j.0022-3042.2001.00756.x
Broadwell RD, Balin BJ, Salcman M (1988) Transcytotic pathway for blood-borne protein through the blood–brain barrier. Proc Natl Acad Sci U S A 85:632–636. doi:10.1073/ pnas.85.2.632
Cabezas R, Ávila M, Gonzalez J, El-Bachá RS, Báez E, García-Segura LM, Jurado Coronel JC, Capani F, Cardona-Gomez GP, Barreto GE (2014) Astrocytic modulation of blood brain barrier: perspectives on Parkinson’s disease. Front Cell Neurosci 8:211. doi:10.3389/fncel.2014.00211
Campos-Bedolla P, Walter FR, Veszelka S, Deli MA (2014) Role of the blood-brain barrier in the nutrition of the central nervous system. Arch Med Res 45:610e638
Cardoso BR, Cominetti C, Cozzolino SM (2013) Importance and management of micronutrient deficiencies in patients with Alzheimer’s disease. Clin Interv Aging 8:531–542. doi:10.2147/CIA.S27983
Chen Y, Liu L (2012) Modern methods for delivery of drugs across the blood–brain barrier. Adv Drug Deliv Rev 64(7):640–665. ISSN 0169-409X, http://dx.doi.org/10.1016/j.addr.2011.11.010
Chiba H, Osanai M, Murata M, Kojima T, Sawada N (2008) Transmembrane proteins of tight junctions. Biochim Biophys Acta (BBA) – Biomembr 1778(3):588–600. ISSN 0005-2736, http://dx.doi.org/10.1016/j.bbamem.2007.08.017
Choi YK, Kim KW (2008) Blood-neural barrier: its diversity and coordinated cell-to-cell communication. BMB Rep 41:345–352
Chrousos GP (2009) Stress and disorders of the stress system. Nat Rev Endocrinol 5(7):374–381
Cipolla MJ (2006) Stroke and the blood-brain interface. In: Dermietzel R, Spray DC, Nedergaard M (eds) Blood-brain barriers: from ontogeny to artificial interfaces, vol 1. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. doi:10.1002/9783527611225.ch25
Ciurea A, Mindruta I, Maliia MD, Ciurea A, Ciurea J, Barborica A, Donos C, Casanova MF, Opris I (2015) Modular signatures and neural avalanches in epileptic brain networks. In: Recent advances on the modular organization of the cortex. Springer, Dordrecht. doi:10.1007/978-94-017-9900-3
Clawson CC, Hartmann JF, Vernier RL (1966) Electron microscopy of the effect of gram-negative endotoxin on the blood-brain barrier. J Comp Neurol 127(2):183–198
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(1):46–56
Davies DC (2002) Blood-brain barrier breakdown in septic encephalopathy and brain tumours. J Anat 200(6):639–646
De Klerk OL, Bosker FJ, Willemsen ATM, Van Waarde A, Visser AKD, de Jager T, Dagyte G, Den Boer JA, Dierckx RA, Meerlo P (2010) Chronic stress and antidepressant treatment have opposite effects on P-glycoprotein at the blood-brain barrier: an experimental PET study in rats. J Psychopharmacol 24(8):1237–1242. doi:10.1177/0269881109349840
De Klerk OL, Bosker FJ, Luurtsema G, Nolte IM, Dierckx R, Den Boer JA et al (2011) The role of p-glycoprotein in psychiatric disorders: a reliable guard of the brain? Cent Nerv Syst Agents Med Chem 11:197–209. doi:10.2174/187152411798047744
Elahy M, Jackaman C, Mamo JC et al (2015) Blood-brain barrier dysfunction developed during normal aging is associated with inflammation and loss of tight junctions but not with leukocyte recruitment. Immun Ageing 12:2
Enciu A-M, Popescu BO (2013) Is there a causal link between inflammation and dementia? Biomed Res Int 2013:316495. doi:10.1155/2013/316495
Faraco G, Wijasa TS, Park L, Moore J, Anrather J, Iadecola C (2014) Water deprivation induces neurovascular and cognitive dysfunction through vasopressin-induced oxidative stress. J Cereb Blood Flow Metab 34(5):852–860. doi:10.1038/jcbfm.2014.24
Fernstrom JD (2005) Branched-chain amino acids and brain function. J Nutr 135(6 Suppl):1539S–1546S
Fernstrom JD (2013) Large neutral amino acids: dietary effects on brain neurochemistry and function. Amino Acids 45:419. doi:10.1007/s00726-012-1330-y
Fiorentino M, Sapone A, Senger S, Camhi SS, Kadzielski SM, Buie TM, Kelly DL, Cascella N, Fasano A (2016) Blood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism Brain Cogn Behav 7:49. doi:10.1186/s13229-016-0110-z
Foti Cuzzola V, Galuppo M, Iori R et al (2013) Beneficial effects of (RS)-glucoraphanin on the tight junction dysfunction in a mouse model of restraint stress. Life Sci 93(7):288–305
Freeman RB, Sheff MF, Maher JF, Schreiner GE (1962) The blood-cerebrospinal fluid barrier in uremia. Ann Intern Med 56:233–240
Frostig RD, Lieke EE, Ts’o DY, Grinvald A (1990) Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. Proc Natl Acad Sci U S A 87(16):6082–6086
Fukui K, Onodera K, Shinkai T, Suzuki S, Urano S (2001) Impairment of learning and memory in rats caused by oxidative stress and aging, and changes in antioxidative defense systems. Ann N Y Acad Sci 928:168–175. doi:10.1111/j.1749-6632.2001.tb05646.x
Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123(6):1777–1788. doi:10.1083/jcb.123.6.1777
Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N (2015) Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Ann Neurol 78:887–900. doi:10.1002/ana.24512
Haleem DJ (2012) Serotonin neurotransmission in anorexia nervosa. Behav Pharmacol 23:478–495
Hall CN, Reynell C, Gesslein B et al (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508(7494):55–60. doi:10.1038/nature13165
Hanin I (1996) The Gulf War, stress and a leaky blood-brain barrier. Nat Med 2(12):1307–1308
Hanstock TL, Mallet PE, Clayton EH (2010) Increased plasma d-lactic acid associated with impaired memory in rats. Physiol Behav 101:653–659
Hawkins BT, Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57(2):173–185
Heye AK, Culling RD, Valdés Hernández Mdel C, Thrippleton MJ, Wardlaw JM (2014) Assessment of blood-brain barrier disruption using dynamic contrast-enhanced MRI. A systematic review. Neuroimag Clin 6:262–274
Hsu TM, Kanoski SE (2014) Blood-brain barrier disruption: mechanistic links between Western diet consumption and dementia. Front Aging Neurosci 6:88
Huber L, Goense J, Kennerley AJ, Trampel R, Guidi M, Reimer E, Ivanov D, Neef N, Gauthier CJ, Turner R, Möller HE (2015) Cortical lamina-dependent blood volume changes in human brain at 7T. NeuroImage 107:23–33. doi:10.1016/j.neuroimage.2014.11.046
Hughes S (2016) Drug targeting blood-brain barrier ‘Hopeful’ in stroke – Medscape. Coverage from the European Stroke Organisation Conference (ESOC) 2016
Huneau C, Benali H, Chabriat H (2015) Investigating human neurovascular coupling using functional neuroimaging: a critical review of dynamic models. Front Neurosci 9:467. doi:10.3389/fnins.2015.00467
Itoh M, Sasaki H, Furuse M, Ozaki H, Kita T, Tsukita S (2001) Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions. J Cell Biol 154(3):491–498. doi:10.1083/jcb.200103047
Jenkins TA, Nguyen JCD, Polglaze KE, Bertrand PP (2016) Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain axis. Forum Nutr 8(1):56. doi:10.3390/nu8010056
Kanoski SE (2012) Cognitive and neuronal systems underlying obesity. Physiol Behav 106(3):337–344
Kanoski SE, Zhang Y, Zheng W, Davidson TL (2010) The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat. J Alzheimers Dis 21(1):207–219
Kassner A, Merali Z (2015) Assessment of blood-brain barrier disruption in stroke. Stroke 46(11):3310–3315
Kastin AJ, Akerstrom V (2001) Pretreatment with glucose increases entry of urocortin into mouse brain. Peptides 22(5):829–834. ISSN 0196-9781, http://dx.doi.org/10.1016/S0196-9781(01)00397-7
Kennedy DO (2016) B vitamins and the brain: mechanisms, dose and efficacy-a review. Nutrients 8:68. doi:10.3390/nu8020068
Kleinfeld D, Mitra PP, Helmchen F, Denk W (1998) Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. Proc Natl Acad Sci U S A 95(26):15741–15746
Kong SD, Lee J, Ramachandran S et al (2012) Magnetic targeting of nanoparticles across the intact blood-brain barrier. J Control Release 164(1):49–57
Kuschinsky W, Paulson OB (1992) Capillary circulation in the brain. Cerebrovasc Brain Metab Rev 4:261–286
Leigh R, Christensen S, Campbell BC et al (2016) Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology 87(3):263–269
Leybaert L (2005) Neurobarrier coupling in the brain: a partner of neurovascular and neurometabolic coupling? J Cereb Blood Flow Metab 25:2–16
Li W, Busu C, Circu ML, Aw TY (2012) Glutathione in Cerebral Microvascular Endothelial Biology and Pathobiology: Implications for Brain Homeostasis. Int J Cell Biol 2012:434971., 14 pages. doi:10.1155/2012/434971
Lim DC, Pack AI (2014) Obstructive sleep apnea and cognitive impairment: addressing the blood-brain barrier. Sleep Med Rev 18:35–48. doi:10.1016/j.smrv.2012.12.003
Magistretti PJ (2000) Cellular bases of functional brain imaging: insights from neuron-glia metabolic coupling. Brain Res 886:108–112
Magistretti PJ (2009) Role of glutamate in neuron-glia metabolic coupling. Am J Clin Nutr 90:875S–880S
Marques F, Sousa JC, Sousa N, Palha JA (2013) Blood–brain-barriers in aging and in Alzheimer’s disease. Mol Neurodegener 8:38. doi:10.1186/1750–1326–8-38
Mathiesen C, Caesar K, Thomsen K, Hoogland TM, Witgen BM, Brazhe A, Lauritzen M (2011) Activity-dependent increases in local oxygen consumption correlate with postsynaptic currents in the mouse cerebellum in vivo. J Neurosci 31(50):18327–18337. doi:10.1523/JNEUROSCI.4526-11.2011
McArthur S, Loiola RA, Maggioli E, Errede M, Virgintino D, Solito E (2016) The restorative role of annexin A1 at the blood–brain barrier. Fluids Barriers CNS 13:17. doi:10.1186/s12987-016-0043-0
McCaffrey G, Staatz WD, Quigley CA, Nametz N, Seelbach MJ, Campos CR, Brooks TA, Egleton RD, Davis TP (2007) Tight junctions contain oligomeric protein assembly critical for maintaining blood-brain barrier integrity in vivo. J Neurochem 103:2540–2555
Mccoll BW, Rothwell NJ, Allan SM (2008) Systemic inflammation alters the kinetics of cerebrovascular tight junction disruption after experimental stroke in mice. J Neurosci 28(38):9451–9462
Montagne A, Barnes SR, Sweeney MD et al (2015) Blood-brain barrier breakdown in the aging human hippocampus. Neuron 85(2):296–302
Mosienko V, Teschemacher AG, Kasparov S (2015) Is L-lactate a novel signaling molecule in the brain? J Cereb Blood Flow Metabol 35:1069–1075
Murata M, Kojima T, Yamamoto T, Go M, Takano K, Osanai M, Chiba H, Sawada N (2005) Down-regulation of survival signaling through MAPK and Akt in occludin-deficient mouse hepatocytes in vitro. Exp Cell Res 310(1):140–151. ISSN 0014-4827, http://dx.doi.org/10.1016/j.yexcr.2005.07.017
Najjar S, Pearlman DM, Alper K, Najjar A, Devinsky O (2013) Neuroinflammation and psychiatric illness. J Neuroinflammation 10:43
Neuwelt EA, Bauer B, Fahlke C et al (2011) Engaging neuroscience to advance translational research in brain barrier biology. Nat Rev Neurosci 12(3):169–182. doi:10.1038/nrn2995
Newman LA, Korol DL, Gold PE (2011) Lactate produced by glycogenolysis in astrocytes regulates memory processing. PLoS One 6:e28427
Nielsen S, Smith BL, Christensen EI, Agre P (1993) Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. Proc Natl Acad Sci U S A 90:7275–7279
Nierwinska K (2008) Blood-brain barrier and exercise – a short review. J Human Kinet 19:83–92., ISSN (Online) 1899-7562, ISSN (Print) 1640-5544
Obermeier B, Daneman R, Ransohoff RM (2013) Development, maintenance and disruption of the blood-brain barrier. Nat Med 19:1584–1596. doi:10.1038/nm.3407
O’Kane RL, Hawkins RA (2003) Na+-dependent transport of large neutral amino acids occurs at the abluminal membrane of the blood-brain barrier. Am J Physiol Endocrinol Metabol 285(6):E1167–E1173. doi:10.1152/ajpendo.00193.2003
Pan W, Akerstrom V, Zhang J, Pejovic V, Kastin AJ (2004) Modulation of feeding-related peptide/ protein signals by the blood–brain barrier. J Neurochem 90:455–461
Pardridge WM (1999) Blood-brain barrier biology and methodology. J Neurovirol 5:556–569
Pardridge WM (2007a) Blood-brain barrier delivery of protein and non-viral gene therapeutics with molecular Trojan horses. J Control Release 122(3):345–348. doi:10.1016/j.jconrel.2007.04.001
Pardridge WM (2007b) Blood-brain barrier delivery. Drug Discov Today 12(1–2):54–61
Paulson OB (2002) Blood-brain barrier, brain metabolism and cerebral blood flow. Eur Neuropsychopharmacol 12:495–501
Petty MA, Lo EH (2002) Junctional complexes of the blood–brain barrier: permeability changes in neuroinflammation. Prog Neurobiol 68(5):311–323. ISSN 0301-0082
Phillips C, Baktir MA, Srivatsan M, Salehi A (2014) Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Front Cell Neurosci 8:170. doi:10.3389/fncel.2014.00170
Popescu BO, Toescu EC, Popescu LM, Bajenaru O, Muresanu DF, Schultzberg M, Bogdanovic N (2009) Blood-brain barrier alterations in ageing and dementia. J Neurol Sci 283(1–2):99–106
Potschka H (2010) Transporter hypothesis of drug-resistant epilepsy: challenges for pharmacogenetic approaches. Pharmacogenomics 11:1427–1438
Prasad S, Sajja RK, Naik P, Cucullo L (2014) Diabetes mellitus and blood-brain barrier dysfunction: an overview. J Pharmacovigil 2(2):125
Rapoport SI (1976) Blood-brain barrier in physiology and medicine. Raven Press, New York
Rehder D, Iden S, Nasdala I, Wegener J, Meyer Zu Brickwedde MK, Vestweber D, Ebnet K (2006) Junctional adhesion molecule-A participates in the formation of apico-basal polarity through different domains. Exp Cell Res 312(17):3389–3403. ISSN 0014-4827, http://dx.doi.org/10.1016/j.yexcr.2006.07.004
Rezayat E, Toostani IG (2016) A review on brain stimulation using low intensity focused ultrasound. Basic Clin Neurosci 7(3):187–194
Riske L, Thomas RK, Baker GB, Dursun SM (2017) Lactate in the brain: an update on its relevance to brain energy, neurons, glia and panic disorder. Therapeut Adv Psychopharmacol 7(2):85–89. doi:10.1177/2045125316675579
Saeed AA, Genové G, Li T et al (2014) Effects of a disrupted blood-brain barrier on cholesterol homeostasis in the brain. J Biol Chem 289(34):23712–23722. doi:10.1074/jbc.M114.556159
Sántha P, Veszelka S, Hoyk Z, Mészáros M, Walter FR, Tóth AE, Kiss L, Kincses A, Oláh Z, Seprényi G, Rákhely G, Dér A, Pákáski M, Kálmán J, Kittel Á, Deli MA (2016) Restraint stress-induced morphological changes at the blood-brain barrier in adult rats. Front Mol Neurosci 8:88. doi:10.3389/fnmol.2015.00088
Schoknecht K, David Y, Heinemann U (2015) The blood-brain barrier-gatekeeper to neuronal homeostasis: clinical implications in the setting of stroke. Semin Cell Dev Biol 38:35–42. doi:10.1016/j.semcdb.2014.10.004. Epub 2014 Nov 7
Schroeter ML, Abdul-khaliq H, Krebs M, Diefenbacher A, Blasig IE (2008) Serum markers support disease-specific glial pathology in major depression. J Affect Disord 111(2–3):271–280
Schurr A, Miller JJ, Payne RS, Rigor BM (1999) An increase in lactate output by brain tissue serves to meet the energy needs of glutamate-activated neurons. J Neurosci 19:34–39
Sendrowski K, Sobaniec W, Sobaniec-lotowska ME, Lewczuk P (2004) S-100 protein as marker of the blood-brain barrier disruption in children with internal hydrocephalus and epilepsy – a preliminary study. Rocz Akad Med Bialymst 49(Suppl 1):236–238
Serlin Y, Shelef I, Knyazer B, Friedman A (2015) Anatomy and physiology of the blood-brain barrier. Semin Cell Dev Biol 38:2–6. doi:10.1016/j.semcdb.2015.01.002
Shalev H, Serlin Y, Friedman A (2009) Breaching the blood-brain barrier as a gate to psychiatric disorder. Cardiovasc Psychiatry Neurol 2009, Article ID 278531, 7 pages
Siegel GJ, Agranoff BW, Albers RW et al (eds) (1999) Basic neurochemistry: molecular, cellular and medical aspects, 6th edn. Lippincott-Raven, Philadelphia
Siesjö BK (1978) Brain energy metabolism. Wiley, New York
Simpson IA, Appel NM, Hokari M, Oki J, Holman GD, Maher F, Koehler-Stec EM, Vannucci SJ, Smith QR (1999) Blood-brain barrier glucose transporter. J Neurochem 72:238–247. doi:10.1046/j.1471-4159.1999.0720238.x
Skelton KH, Owens MJ, Nemeroff CB (2000) The neurobiology of urocortin. Regul Pept 93(1–3):85–92. doi:10.1016/S0167-0115(00)00180-4
Sloan CDK, Nandi P, Linz TH, Aldrich JV, Audus KL, Lunte SM (2012) Analytical and biological methods for probing the blood-brain barrier. Ann Rev Analyt Chem (Palo Alto, Calif) 5:505–531. doi:10.1146/annurev-anchem-062011-143002
Souza PS, Gonçalves ED, Pedroso GS et al (2017) Physical exercise attenuates experimental autoimmune encephalomyelitis by inhibiting peripheral immune response and blood-brain barrier disruption. Mol Neurobiol 54(6):4723–4737
Stamatovic SM, Keep RF, Andjelkovic AV (2008) Brain endothelial cell-cell junctions: how to “open” the blood brain barrier. Curr Neuropharmacol 6(3):179–192. doi:10.2174/157015908785777210
Stanger O, Fowler B, Piertzik K, Huemer M, Haschke-Becher E, Semmler A, Lorenzl S, Linnebank M (2014) Homocysteine, folate and vitamin B12 in neuropsychiatric diseases: review and treatment recommendations. Expert Rev Neurother 9(9):1393–1412. doi:10.1586/ern.09.75
Stoquart-ElSankari S, Baledent O, Gondry-Jouet C, Makki M, Godefroy O, Meyer ME (2007) Aging effects on cerebral blood and cerebrospinal fluid flows. J Cereb Blood Flow Metab 27:1563–1572
Sukriti N, Begley DJ (2005) Blood–brain barrier, exchange of metabolites and gases. In: Kalimo H (ed) Pathology and genetics. Cerebrovascular diseases. ISN Neuropathology Press, Basel, pp 22–29
Sykova E, Nicholson C (2008) Diffusion in brain extracellular space. Physiol Rev 88:1277–1340
Takanaga H, Ohtsuki S, Hosoya KI, Terasaki T (2001) GAT2/BGT-1 as a system responsible for the transport of γ-aminobutyric acid at the mouse blood–brain barrier. J Cereb Blood Flow Metab 21(10):1232–1239
Tang VW, Goodenough DA (2003) Paracellular ion channel at the tight junction. Biophys J 84(3):1660–1673
Tărlungeanu DC, Deliu E, Dotter CP, Kara M, Janiesch PC, Scalise M, Galluccio M, Tesulov M, Morelli E, Sonmez FM, Bilguvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben-Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan KE, Caglayan AO, Gunel M, Gleeson JG, Novarino G (2016) Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell 167(6):1481–1494. e18, ISSN 0092-8674, http://dx.doi.org/10.1016/j.cell.2016.11.013
Tietz S, Engelhardt B (2015) Brain barriers: crosstalk between complex tight junctions and adherens junctions. J Cell Biol 209:493–506
Ueno M (2007) Molecular anatomy of the brain endothelial barrier: an overview of the distributional features. Curr Med Chem 14:1199–1206
Vidu R, Rahman M, Mahmoudi M, Enachescu M, Poteca TD, Opris I (2014) Nanostructures: a platform for brain repair and augmentation. Front Syst Neurosci 8:91
Vogel J, Kuschinsky W (1996) Decreased heterogeneity of capillary plasma flow in the rat whisker-barrel cortex during functional hyperemia. J Cereb Blood Flow Metab 16:1300–1306
Ward NL, Lamanna JC (2004) The neurovascular unit and its growth factors: coordinated response in the vascular and nervous systems. Neurol Res 26:870–883
Watson P, Shirreffs SM, Maughan RJ (2005) Blood-brain barrier integrity may be threatened by exercise in a warm environment. Am J Physiol Regul Integr Comp Physiol 288(6):R1689–R1694
Weekman EM, Wilcock DM (2016) J Alzheimers Dis 49(4):893–903. doi:10.3233/JAD-150759
Wilhelm I, Nyúl-Tóth Á, Suciu M, Hermenean A, Krizbai IA (2016) Heterogeneity of the blood-brain barrier. Tissue Barriers. doi:10.1080/21688370.2016.1143544
Wilson RS, Arnold SE, Schneider JA, Kelly JF, Tang Y, Bennett DA (2006) Chronic psychological distress and risk of Alzheimer’s disease in old age. Neuroepidemiology 27(3):143–153
Wolburg H, Lippoldt A (2002) Tight junctions of the blood-brain barrier: development, composition and regulation. Vasc Pharmacol 38:323–337
Wolburg H, Noell S, Mack A et al (2009) Cell Tissue Res 335:75. doi:10.1007/s00441-008-0658-9
Wolff G, Davidson SJ, Wrobel JK, Toborek M (2015) Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation. Biochem Biophys Res Commun 463(4):811–817
Wurtman RJ (1987) Dietary treatments that affect brain neurotransmitters. Effects on calorie and nutrient intake. Ann N Y Acad Sci 499:179–190
Xing Y, Liu J, Xu J et al (2015) Association between plasma leptin and estrogen in female patients of amnestic mild cognitive impairment. Dis Markers 2015:450237. doi:10.1155/2015/450237
Yang Y, Rosenberg GA (2011) Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke 42(11):3323–3328
Young GB, Bolton CF, Archibald YM, Austin TW, Wells GA (1992) The electroencephalogram in sepsis-associated encephalopathy. J Clin Neurophysiol 9(1):145–152
Zhang J, Liu Q (2015) Cholesterol metabolism and homeostasis in the brain. Protein Cell 6(4):254–264. doi:10.1007/s13238-014-0131-3
Zhao BQ, Wang S, Kim HY, Storrie H, Rosen BR, Mooney DJ, Wang X, Lo EH (2006) Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat Med 12:441–445
Zlokovic BV (2008) The blood–brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178–201. doi:10.1016/j.neuron.2008.01.003
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Zăgrean, AM., Ianosi, B., Sonea, C., Opris, I., Zăgrean, L. (2017). Blood-Brain Barrier and Cognitive Function. In: Opris, I., Casanova, M.F. (eds) The Physics of the Mind and Brain Disorders. Springer Series in Cognitive and Neural Systems, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-319-29674-6_32
Download citation
DOI: https://doi.org/10.1007/978-3-319-29674-6_32
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-29672-2
Online ISBN: 978-3-319-29674-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)