Skip to main content
SpringerLink
Log in

Blood-Brain Barrier and Cognitive Function

  • Chapter
  • First Online:
The Physics of the Mind and Brain Disorders

Part of the book series: Springer Series in Cognitive and Neural Systems ((SSCNS,volume 11))

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.

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

Access this chapter

Log in via an institution

Institutional subscriptions

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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Abbott NJ (2004) Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem Int 45:545–552

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ (2010) Structure and function of the blood–brain barrier. Neurobiol Dis 37:13–25

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Amiry-Moghaddam M, Ottersen OP (2003) The molecular basis of water transport in the brain. Nat Rev Neurosci 4:991–1001

    Article  CAS  Google Scholar 

  • Andras IE, Toborek M (2016) Extracellular vesicles of the blood-brain barrier. Tissue Barriers 4(1):e1131804

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • Armulik A, Genové G, Mäe M et al (2010) Pericytes regulate the blood-brain barrier. Nature 468(7323):557–561

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Bar T (1980) The vascular system of the cerebral cortex. Springer, Berlin. doi:10.1007/978-3-642-67432-7

    Book  Google Scholar 

  • Barros LF (2013) Metabolic signaling by lactate in the brain. Trends Neurosci 36(7):396–404

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Choi YK, Kim KW (2008) Blood-neural barrier: its diversity and coordinated cell-to-cell communication. BMB Rep 41:345–352

    Article  CAS  Google Scholar 

  • Chrousos GP (2009) Stress and disorders of the stress system. Nat Rev Endocrinol 5(7):374–381

    Article  CAS  Google Scholar 

  • 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

    Chapter  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Davies DC (2002) Blood-brain barrier breakdown in septic encephalopathy and brain tumours. J Anat 200(6):639–646

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Fernstrom JD (2005) Branched-chain amino acids and brain function. J Nutr 135(6 Suppl):1539S–1546S

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Freeman RB, Sheff MF, Maher JF, Schreiner GE (1962) The blood-cerebrospinal fluid barrier in uremia. Ann Intern Med 56:233–240

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Haleem DJ (2012) Serotonin neurotransmission in anorexia nervosa. Behav Pharmacol 23:478–495

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Hanin I (1996) The Gulf War, stress and a leaky blood-brain barrier. Nat Med 2(12):1307–1308

    Article  CAS  Google Scholar 

  • Hanstock TL, Mallet PE, Clayton EH (2010) Increased plasma d-lactic acid associated with impaired memory in rats. Physiol Behav 101:653–659

    Article  CAS  Google Scholar 

  • Hawkins BT, Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57(2):173–185

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Hsu TM, Kanoski SE (2014) Blood-brain barrier disruption: mechanistic links between Western diet consumption and dementia. Front Aging Neurosci 6:88

    Article  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Kanoski SE (2012) Cognitive and neuronal systems underlying obesity. Physiol Behav 106(3):337–344

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Kassner A, Merali Z (2015) Assessment of blood-brain barrier disruption in stroke. Stroke 46(11):3310–3315

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Kennedy DO (2016) B vitamins and the brain: mechanisms, dose and efficacy-a review. Nutrients 8:68. doi:10.3390/nu8020068

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Kuschinsky W, Paulson OB (1992) Capillary circulation in the brain. Cerebrovasc Brain Metab Rev 4:261–286

    CAS  Google Scholar 

  • Leigh R, Christensen S, Campbell BC et al (2016) Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology 87(3):263–269

    Article  Google Scholar 

  • Leybaert L (2005) Neurobarrier coupling in the brain: a partner of neurovascular and neurometabolic coupling? J Cereb Blood Flow Metab 25:2–16

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Magistretti PJ (2000) Cellular bases of functional brain imaging: insights from neuron-glia metabolic coupling. Brain Res 886:108–112

    Article  CAS  Google Scholar 

  • Magistretti PJ (2009) Role of glutamate in neuron-glia metabolic coupling. Am J Clin Nutr 90:875S–880S

    Article  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Montagne A, Barnes SR, Sweeney MD et al (2015) Blood-brain barrier breakdown in the aging human hippocampus. Neuron 85(2):296–302

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Najjar S, Pearlman DM, Alper K, Najjar A, Devinsky O (2013) Neuroinflammation and psychiatric illness. J Neuroinflammation 10:43

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Newman LA, Korol DL, Gold PE (2011) Lactate produced by glycogenolysis in astrocytes regulates memory processing. PLoS One 6:e28427

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Pardridge WM (1999) Blood-brain barrier biology and methodology. J Neurovirol 5:556–569

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Pardridge WM (2007b) Blood-brain barrier delivery. Drug Discov Today 12(1–2):54–61

    Article  CAS  Google Scholar 

  • Paulson OB (2002) Blood-brain barrier, brain metabolism and cerebral blood flow. Eur Neuropsychopharmacol 12:495–501

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Potschka H (2010) Transporter hypothesis of drug-resistant epilepsy: challenges for pharmacogenetic approaches. Pharmacogenomics 11:1427–1438

    Article  CAS  Google Scholar 

  • Prasad S, Sajja RK, Naik P, Cucullo L (2014) Diabetes mellitus and blood-brain barrier dysfunction: an overview. J Pharmacovigil 2(2):125

    Google Scholar 

  • Rapoport SI (1976) Blood-brain barrier in physiology and medicine. Raven Press, New York

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Rezayat E, Toostani IG (2016) A review on brain stimulation using low intensity focused ultrasound. Basic Clin Neurosci 7(3):187–194

    CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Google Scholar 

  • Siegel GJ, Agranoff BW, Albers RW et al (eds) (1999) Basic neurochemistry: molecular, cellular and medical aspects, 6th edn. Lippincott-Raven, Philadelphia

    Google Scholar 

  • Siesjö BK (1978) Brain energy metabolism. Wiley, New York

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Google Scholar 

  • Sykova E, Nicholson C (2008) Diffusion in brain extracellular space. Physiol Rev 88:1277–1340

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Tang VW, Goodenough DA (2003) Paracellular ion channel at the tight junction. Biophys J 84(3):1660–1673

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Tietz S, Engelhardt B (2015) Brain barriers: crosstalk between complex tight junctions and adherens junctions. J Cell Biol 209:493–506

    Article  CAS  Google Scholar 

  • Ueno M (2007) Molecular anatomy of the brain endothelial barrier: an overview of the distributional features. Curr Med Chem 14:1199–1206

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Weekman EM, Wilcock DM (2016) J Alzheimers Dis 49(4):893–903. doi:10.3233/JAD-150759

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Wolburg H, Lippoldt A (2002) Tight junctions of the blood-brain barrier: development, composition and regulation. Vasc Pharmacol 38:323–337

    Article  CAS  Google Scholar 

  • Wolburg H, Noell S, Mack A et al (2009) Cell Tissue Res 335:75. doi:10.1007/s00441-008-0658-9

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Wurtman RJ (1987) Dietary treatments that affect brain neurotransmitters. Effects on calorie and nutrient intake. Ann N Y Acad Sci 499:179–190

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Yang Y, Rosenberg GA (2011) Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke 42(11):3323–3328

    Article  CAS  Google Scholar 

  • Young GB, Bolton CF, Archibald YM, Austin TW, Wells GA (1992) The electroencephalogram in sepsis-associated encephalopathy. J Clin Neurophysiol 9(1):145–152

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Physiology and Neuroscience, “Carol Davila” University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474, Bucharest, Romania

    Ana-Maria Zăgrean & Leon Zăgrean

  2. Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474, Bucharest, Romania

    Bogdan Ianosi

  3. Department of Neurology, Division of Neurocritical Care, Medical University of Innsbruck, Innsbruck, Austria

    Bogdan Ianosi

  4. Department of Veterinary Medicine, University of Agronomical Sciences and Veterinary Medicine, Bucharest, Romania

    Cosmin Sonea & Ioan Opris

  5. Miami Project to Cure Paralysis, Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA

    Ioan Opris

Authors
  1. Ana-Maria Zăgrean
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bogdan Ianosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cosmin Sonea
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ioan Opris
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Leon Zăgrean
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana-Maria Zăgrean .

Editor information

Editors and Affiliations

  1. Miami Project to Cure Paralysis, Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA

    Ioan Opris

  2. Greenville Health System, University of South Carolina, School of Medicine Greenville, Greenville, SC, USA

    Manuel F. Casanova

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

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

Publish with us

Policies and ethics

Search

Navigation