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Fluids and Barriers of the CNS
Published in: Fluids and Barriers of the CNS 1/2016

Open Access 01-12-2016 | Review

The restorative role of annexin A1 at the blood–brain barrier

Authors: Simon McArthur, Rodrigo Azevedo Loiola, Elisa Maggioli, Mariella Errede, Daniela Virgintino, Egle Solito

Published in: Fluids and Barriers of the CNS | Issue 1/2016

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Abstract

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood–brain barrier damage in disease and aging.
Literature
1.
Sankowski R, Mader S, Valdés-Ferrer SI. Systemic inflammation and the brain: novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration. Front Cell Neurosci. 2015;9:28.PubMedPubMedCentralCrossRef
2.
Magistretti PJ, Allaman I. A cellular perspective on brain energy metabolism and functional imaging. Neuron. 2015;86:883–901.PubMedCrossRef
3.
4.
5.
Chow BW, Gu C. The molecular constituents of the blood–brain barrier. Trends Neurosci. 2015;38:598–608.PubMedCrossRef
6.
Sun H, Dai H, Shaik N, Elmquist WF. Drug efflux transporters in the CNS. Adv Drug Deliv Rev. 2003;55:83–105.PubMedCrossRef
7.
Sanchez-Covarrubias L, Slosky LM, Thompson BJ, Davis TP, Ronaldson PT. Transporters at CNS barrier sites: obstacles or opportunities for drug delivery? Curr Pharm Des. 2014;20:1422–49.PubMedPubMedCentralCrossRef
8.
Haseloff RF, Dithmer S, Winkler L, Wolburg H, Blasig IE. Transmembrane proteins of the tight junctions at the blood–brain barrier: structural and functional aspects. Semin Cell Dev Biol. 2015;38:16–25.PubMedCrossRef
9.
10.
Carman CV, Sage PT, Sciuto TE, de la Fuente MA, Geha RS, Ochs HD, et al. Transcellular diapedesis is initiated by invasive podosomes. Immunity. 2007;26:784–97.PubMedPubMedCentralCrossRef
11.
Stieger B, Gao B. Drug transporters in the central nervous system. Clin Pharmacokinet. 2015;54:225–42.PubMedCrossRef
12.
Qosa H, Miller DS, Pasinelli P, Trotti D. Regulation of ABC efflux transporters at blood–brain barrier in health and neurological disorders. Brain Res. 2015;1628:298–316.PubMedCrossRef
13.
Salameh TS, Banks WA. Delivery of therapeutic peptides and proteins to the CNS. Adv Pharmacol. 2014;71:277–99.PubMedCrossRef
14.
Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ. Structure and function of the blood–brain barrier. Neurobiol Dis. 2010;37:13–25.PubMedCrossRef
15.
Thomsen MS, Birkelund S, Burkhart A, Stensballe A, Moos T. Synthesis and deposition of basement membrane proteins by primary brain capillary endothelial cells in a murine model of the blood–brain barrier. J Neurochem. 2016. doi:10.​1111/​jnc.​13747.
16.
Hallmann R, Horn N, Selg M, Wendler O, Pausch F, Sorokin LM. Expression and function of laminins in the embryonic and mature vasculature. Physiol Rev. 2005;85:979–1000.PubMedCrossRef
17.
Engelhardt B, Sorokin L. The blood–brain and the blood-cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol. 2009;31:497–511.PubMedCrossRef
18.
del Zoppo GJ, Milner R. Integrin-matrix interactions in the cerebral microvasculature. Arterioscler Thromb Vasc Biol. 2006;26:1966–75.PubMedCrossRef
19.
Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab NIH Public Access. 2007;27:1766–91.CrossRef
20.
Brkic M, Balusu S, Libert C, Vandenbroucke RE. Friends or foes: matrix metalloproteinases and their multifaceted roles in neurodegenerative diseases. Mediators Inflamm. 2015;2015:620581.PubMedPubMedCentralCrossRef
21.
Bruschi F, Pinto B. The significance of matrix metalloproteinases in parasitic infections involving the central nervous system. Pathog. 2013;2:105–29.CrossRef
22.
Heo JH, Han SW, Lee SK. Free radicals as triggers of brain edema formation after stroke. Free Radic Biol Med. 2005;39:51–70.PubMedCrossRef
23.
Rosell A, Ortega-Aznar A, Alvarez-Sabín J, Fernández-Cadenas I, Ribó M, Molina CA, et al. Increased brain expression of matrix metalloproteinase-9 after ischemic and hemorrhagic human stroke. Stroke. 2006;37:1399–406.PubMedCrossRef
24.
Muradashvili N, Benton RL, Saatman KE, Tyagi SC, Lominadze D. Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice. Metab Brain Dis. 2015;30:411–26.PubMedCrossRef
25.
Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, et al. Capillary pericytes regulate cerebral blood flow in health and disease. Nature. 2014;508:55–60.PubMedPubMedCentralCrossRef
26.
Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97:512–23.PubMedCrossRef
27.
Hellström M, Gerhardt H, Kalén M, Li X, Eriksson U, Wolburg H, et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol. 2001;153:543–53.PubMedPubMedCentralCrossRef
28.
Liebner S, Corada M, Bangsow T, Babbage J, Taddei A, Czupalla CJ, et al. Wnt/beta-catenin signaling controls development of the blood–brain barrier. J Cell Biol. 2008/10/29 ed. 2008;183:409–17.
29.
Liebner S, Plate KH, Ferguson J, Kelley R, Patterson C, Risau W, et al. Differentiation of the brain vasculature: the answer came blowing by the Wnt. J Angiogenes Res. 2010;2:1.PubMedPubMedCentralCrossRef
30.
Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 2010;68:409–27.PubMedPubMedCentralCrossRef
31.
Yao Y, Chen Z-L, Norris EH, Strickland S. Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity. Nat Commun. 2014;5:3413.PubMedPubMedCentral
32.
Janzer RC, Raff MC. Astrocytes induce blood–brain barrier properties in endothelial cells. Nature. 1987;325:253–7.PubMedCrossRef
33.
Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7:41–53.PubMedCrossRef
34.
Satoh J, Tabunoki H, Yamamura T, Arima K, Konno H. Human astrocytes express aquaporin-1 and aquaporin-4 in vitro and in vivo. Neuropathology. 2007;27:245–56.PubMedCrossRef
35.
36.
37.
Thal DR. The role of astrocytes in amyloid β-protein toxicity and clearance. Exp Neurol. 2012;236:1–5.PubMedCrossRef
38.
39.
Sumi N, Nishioku T, Takata F, Matsumoto J, Watanabe T, Shuto H, et al. Lipopolysaccharide-activated microglia induce dysfunction of the blood–brain barrier in rat microvascular endothelial cells co-cultured with microglia. Cell Mol Neurobiol. 2010;30:247–53.PubMedCrossRef
40.
Nishioku T, Matsumoto J, Dohgu S, Sumi N, Miyao K, Takata F, et al. Tumor necrosis factor-alpha mediates the blood–brain barrier dysfunction induced by activated microglia in mouse brain microvascular endothelial cells. J Pharmacol Sci. 2010;112:251–4.PubMedCrossRef
41.
Andreone BJ, Lacoste B, Gu C. Neuronal and vascular interactions. Annu Rev Neurosci. 2015;38:25–46.PubMedCrossRef
42.
Varatharaj A, Galea I. The blood–brain barrier in systemic inflammation. Immun: Brain Behav; 2016.
43.
Lopez-Ramirez MA, Reijerkerk A, de Vries HE, Romero IA. Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation. FASEB J. 2016;30:2662–72.PubMedCrossRef
44.
Derada Troletti C, de Goede P, Kamermans A, de Vries HE. Molecular alterations of the blood–brain barrier under inflammatory conditions: the role of endothelial to mesenchymal transition. Biochim Biophys Acta Mol Basis Dis. 2016;1862:452–60.CrossRef
45.
Zenaro E, Piacentino G, Constantin G. The blood–brain barrier in Alzheimer’s disease. Dis: Neurobiol; 2016.
46.
Engelhardt B, Ransohoff RM. Capture, crawl, cross: the T cell code to breach the blood–brain barriers. Trends Immunol. 2012;33:579–89.PubMedCrossRef
47.
Zhou L, Yang B, Wang Y, Zhang H-L, Chen R-W, Wang Y-B. Bradykinin regulates the expression of claudin-5 in brain microvascular endothelial cells via calcium-induced calcium release. J Neurosci Res. 2014;92:597–606.PubMedCrossRef
48.
Schwaninger M, Sallmann S, Petersen N, Schneider A, Prinz S, Libermann TA, et al. Bradykinin induces interleukin-6 expression in astrocytes through activation of nuclear factor-kappaB. J Neurochem. 1999;73:1461–6.PubMedCrossRef
49.
Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev. 1988;12:123–37.PubMedCrossRef
50.
McCusker RH, Kelley KW. Immune-neural connections: how the immune system’s response to infectious agents influences behavior. J Exp Biol. 2013;216:84–98.PubMedPubMedCentralCrossRef
51.
Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z, et al. Blood–brain barrier breakdown in the aging human hippocampus. Neuron. 2015;85:296–302.PubMedPubMedCentralCrossRef
52.
Taheri S, Gasparovic C, Huisa BN, Adair JC, Edmonds E, Prestopnik J, et al. Blood–brain barrier permeability abnormalities in vascular cognitive impairment. Stroke. 2011;42:2158–63.PubMedPubMedCentralCrossRef
53.
Popescu BO, Toescu EC, Popescu LM, Bajenaru O, Muresanu DF, Schultzberg M, et al. Blood–brain barrier alterations in ageing and dementia. J Neurol Sci. 2009;283:99–106.PubMedCrossRef
54.
Wardlaw JM, Doubal FN, Valdes-Hernandez M, Wang X, Chappell FM, Shuler K, et al. Blood–brain barrier permeability and long-term clinical and imaging outcomes in cerebral small vessel disease. Stroke. 2013;44:525–7.PubMedCrossRef
55.
van de Haar HJ, Burgmans S, Hofman PAM, Verhey FRJ, Jansen JFA, Backes WH. Blood–brain barrier impairment in dementia: current and future in vivo assessments. Neurosci Biobehav Rev. 2015;49:71–81.PubMedCrossRef
56.
Raz L, Knoefel J, Bhaskar K. The neuropathology and cerebrovascular mechanisms of dementia. Blood Flow Metab: J Cereb; 2015.
57.
Bowman GL, Kaye JA, Moore M, Waichunas D, Carlson NE, Quinn JF. Blood–brain barrier impairment in Alzheimer disease: stability and functional significance. Neurology. 2007;68:1809–14.PubMedPubMedCentralCrossRef
58.
59.
Nelson AR, Sweeney MD, Sagare AP, Zlokovic BV. Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer’s disease. Acta: Biochim Biophys; 2015.
60.
61.
Wang C, Chan JSY, Ren L, Yan JH. Obesity reduces cognitive and motor functions across the lifespan. Neural Plast. 2016;2016:2473081.PubMedPubMedCentral
62.
Ransohoff RM, Brown MA. Innate immunity in the central nervous system. J Clin Invest. 2012/04/03 ed. 2012;122:1164–71.
63.
Ransohoff RM, Engelhardt B. The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol. 2012/08/21 ed. 2012;12:623–35.
64.
Maggioli E, McArthur S, Mauro C, Kieswich J, Kusters DHMHM, Reutelingsperger CPMPM, et al. Estrogen protects the blood–brain barrier from inflammation-induced disruption and increased lymphocyte trafficking. Brain Behav Immun. 2015;51:212–22.PubMedCrossRef
65.
Solito E, McArthur S, Christian H, Gavins F, Buckingham JC, Gillies GE. Annexin A1 in the brain–undiscovered roles? Trends Pharmacol Sci. 2008/02/12 ed. 2008;29:135–42.
66.
Parente L, Solito E. Annexin 1: more than an anti-phospholipase protein. Inflamm Res. 2004;53:125–32.PubMedCrossRef
67.
68.
69.
Solito E, Mulla A, Morris JF, Christian HC, Flower RJ, Buckingham JC. Dexamethasone induces rapid serine-phosphorylation and membrane translocation of annexin 1 in a human folliculostellate cell line via a novel nongenomic mechanism involving the glucocorticoid receptor, protein kinase C, phosphatidylinositol 3-kinase. Endocrinology. 2003/03/18 ed. 2003;144:1164–74.
70.
Solito E, Christian HC, Festa M, Mulla A, Tierney T, Flower RJ, et al. Post-translational modification plays an essential role in the translocation of annexin A1 from the cytoplasm to the cell surface. Faseb J. 2006/05/25 ed. 2006;20:1498–500.
71.
Cirino G, Cicala C, Sorrentino L, Ciliberto G, Arpaia G, Perretti M, et al. Anti-inflammatory actions of an N-terminal peptide from human lipocortin 1. Br J Pharmacol. 1993;108:573–4.PubMedPubMedCentralCrossRef
72.
Kovacic RT, Tizard R, Cate RL, Frey AZ, Wallner BP. Correlation of gene and protein structure of rat and human lipocortin I. Biochemistry. 1991;30:9015–21.PubMedCrossRef
73.
Lopez-Ramirez MA, Wu D, Pryce G, Simpson JE, Reijerkerk A, King-Robson J, et al. MicroRNA-155 negatively affects blood–brain barrier function during neuroinflammation. FASEB J. 2014;28:2551–65.PubMedCrossRef
74.
Solito E, Romero IA, Marullo S, Russo-Marie F, Weksler BB. Annexin 1 binds to U937 monocytic cells and inhibits their adhesion to microvascular endothelium: involvement of the alpha 4 beta 1 integrin. J Immunol. 2000/07/21 ed. 2000;165:1573–81.
75.
Cristante E, McArthur S, Mauro C, Maggioli E, Romero IA, Wylezinska-Arridge M, et al. Feature Article: Identification of an essential endogenous regulator of blood–brain barrier integrity, and its pathological and therapeutic implications. Proc Natl Acad Sci USA. 2013/01/02 ed. 2013;110:832–41.
76.
de la Fuente M, Parra AV. Vesicle aggregation by annexin I: role of a secondary membrane binding site. Biochemistry. 1995;34:10393–9.PubMedCrossRef
77.
McArthur S, Gobbetti T, Kusters DHM, Reutelingsperger CP, Flower RJ, Perretti M. Definition of a novel pathway centered on lysophosphatidic acid to recruit monocytes during the resolution phase of tissue inflammation. J Immunol. 2015;195:1500733.CrossRef
78.
Bena S, Brancaleone V, Wang JM, Perretti M, Flower RJ. Annexin A1 interaction with the FPR2/ALX receptor: identification of distinct domains and downstream associated signaling. J Biol Chem. 2012;287:24690–7.PubMedPubMedCentralCrossRef
79.
McArthur S, Yazid S, Christian H, Sirha R, Flower R, Buckingham J, et al. Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization. Faseb J. 2009/07/25 ed. 2009;23:4000–10.
80.
Cristante E, McArthur S, Mauro C, Maggioli E, Romero IA, Wylezinska-Arridge M, et al. Identification of an essential endogenous regulator of blood–brain barrier integrity, and its pathological and therapeutic implications. Proc Natl Acad Sci USA. 2013;110:832–41.PubMedCrossRef
81.
Solito E, McArthur S, Christian H, Gavins F, Buckingham JC, Gillies GE. Annexin A1 in the brain–undiscovered roles? Trends Pharmacol Sci. 2008;29:135–42.PubMedCrossRef
82.
Luo ZZ, Gao Y, Sun N, Zhao Y, Wang J, Tian B, et al. Enhancing the interaction between annexin-1 and formyl peptide receptors regulates microglial activation to protect neurons from ischemia-like injury. J Neuroimmunol. 2014;276:24–36.PubMedCrossRef
83.
McArthur S, Cristante E, Paterno M, Christian H, Roncaroli F, Gillies GE, et al. Annexin A1: a central player in the anti-inflammatory and neuroprotective role of microglia. J Immunol. 2010/10/22 ed. 2010;185:6317–28.
84.
Solito E, Sastre M. Microglia function in Alzheimer’s disease. Front Pharmacol. 2012/03/01 ed. 2012;3:14.
85.
Ek CJ, Dziegielewska KM, Habgood MD, Saunders NR. Barriers in the developing brain and neurotoxicology. Neurotoxicology. 2012;33:586–604.PubMedCrossRef
86.
Virgintino D, Errede M, Robertson D, Capobianco C, Girolamo F, Vimercati A, et al. Immunolocalization of tight junction proteins in the adult and developing human brain. Histochem Cell Biol. 2004;122:51–9.PubMedCrossRef
87.
Virgintino D, Errede M, Girolamo F, Capobianco C, Robertson D, Vimercati A, et al. Fetal blood–brain barrier P-glycoprotein contributes to brain protection during human development. J Neuropathol Exp Neurol. 2008;67:50–61.PubMedCrossRef
88.
D’Acunto CW, Gbelcova H, Festa M, Ruml T. The complex understanding of annexin A1 phosphorylation. Cell Signal. 2014;26:173–8.PubMedCrossRef
89.
Han G, Tian Y, Duan B, Sheng H, Gao H, Huang J. Association of nuclear annexin A1 with prognosis of patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7:751–9.PubMedPubMedCentral
90.
Farrall AJ, Wardlaw JM. Blood–brain barrier: ageing and microvascular disease–systematic review and meta-analysis. Neurobiol Aging. 2009;30:337–52.PubMedCrossRef
91.
Elahy M, Jackaman C, Mamo JC, Lam V, Dhaliwal SS, Giles C, et al. Blood–brain barrier dysfunction developed during normal aging is associated with inflammation and loss of tight junctions but not with leukocyte recruitment. Immun Ageing. 2015;12:2.PubMedPubMedCentralCrossRef
92.
Boraldi F, Bini L, Liberatori S, Armini A, Pallini V, Tiozzo R, et al. Proteome analysis of dermal fibroblasts cultured in vitro from human healthy subjects of different ages. Proteomics. 2003;3:917–29.PubMedCrossRef
93.
Leoni G, Neumann P-A, Kamaly N, Quiros M, Nishio H, Jones HR, et al. Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J Clin Invest. 2015;125:1215–27.PubMedPubMedCentralCrossRef
94.
Monastyrskaya K, Babiychuk EB, Draeger A, Burkhard FC. Down-regulation of annexin A1 in the urothelium decreases cell survival after bacterial toxin exposure. J Urol. 2013;190:325–33.PubMedCrossRef
95.
Gorlé N, Van Cauwenberghe C, Libert C, Vandenbroucke RE. The effect of aging on brain barriers and the consequences for Alzheimer’s disease development. Mamm Genome. 2016;27:407–20.PubMedCrossRef
96.
Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci. 2011;12:723–38.PubMedPubMedCentral
97.
Sengillo JD, Winkler EA, Walker CT, Sullivan JS, Johnson M, Zlokovic BV. Deficiency in mural vascular cells coincides with blood–brain barrier disruption in Alzheimer’s disease. Brain Pathol. 2013;23:303–10.PubMedCrossRef
98.
Wang S, Voisin M-B, Larbi KY, Dangerfield J, Scheiermann C, Tran M, et al. Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med. 2006;203:1519–32.PubMedPubMedCentralCrossRef
99.
Knott C, Stern G, Wilkin GP. Inflammatory regulators in Parkinson’s disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2. Mol Cell Neurosci. 2000;16:724–39.PubMedCrossRef
100.
Eberhard DA, Brown MD, VandenBerg SR. Alterations of annexin expression in pathological neuronal and glial reactions. Immunohistochemical localization of annexins I, II (p36 and p11 subunits), IV, and VI in the human hippocampus. Am J Pathol. 1994;145:640–9.PubMedPubMedCentral
101.
Perretti M, D’Acquisto F. Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol. 2009;9:62–70.PubMedCrossRef
102.
Lee YH, Song GG. Genome-wide pathway analysis of a genome-wide association study on Alzheimer’s disease. Neurol Sci. 2015;36:53–9.PubMedCrossRef
103.
Burgmans S, van de Haar HJ, Verhey FRJ, Backes WH. Amyloid-β interacts with blood–brain barrier function in dementia: a systematic review. J Alzheimers Dis. 2013;35:859–73.PubMed
104.
Viggars AP, Wharton SB, Simpson JE, Matthews FE, Brayne C, Savva GM, et al. Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: a study in the MRC-CFAS population neuropathology cohort. Neurosci Lett. 2011;505:25–30.PubMedCrossRef
105.
Algotsson A, Winblad B. The integrity of the blood–brain barrier in Alzheimer’s disease. Acta Neurol Scand. 2007;115:403–8.PubMedCrossRef
106.
Deane R, Sagare A, Hamm K, Parisi M, LaRue B, Guo H, et al. IgG-assisted age-dependent clearance of Alzheimer’s amyloid beta peptide by the blood–brain barrier neonatal Fc receptor. J Neurosci. 2005;25:11495–503.PubMedCrossRef
107.
Cignarella A, Bolego C, Pelosi V, Meda C, Krust A, Pinna C, et al. Distinct roles of estrogen receptor-alpha and beta in the modulation of vascular inducible nitric-oxide synthase in diabetes. J Pharmacol Exp Ther. 2009;328:174–82.PubMedCrossRef
108.
Deo AK, Borson S, Link JM, Domino K, Eary JF, Ke B, et al. Activity of P-glycoprotein, a β-amyloid transporter at the blood–brain barrier, is compromised in patients with mild Alzheimer disease. J Nucl Med. 2014;55:1106–11.PubMedPubMedCentralCrossRef
109.
110.
Ortiz GG, Pacheco-Moisés FP, Macías-Islas MÁ, Flores-Alvarado LJ, Mireles-Ramírez MA, González-Renovato ED, et al. Role of the blood–brain barrier in multiple sclerosis. Arch Med Res. 2014;45:687–97.PubMedCrossRef
111.
Walter FR, Veszelka S, Deli MA. Role of the blood–brain barrier in the nutrition of the central nervous system. Arch Med Res. 2014;45:610–38.PubMedCrossRef
112.
Alvarez JI, Cayrol R, Prat A. Disruption of central nervous system barriers in multiple sclerosis. Biochim Biophys Acta. 2011;1812:252–64.PubMedCrossRef
113.
Probst-Cousin S, Kowolik D, Kuchelmeister K, Kayser C, Neundorfer B, Heuss D. Expression of annexin-1 in multiple sclerosis plaques. Neuropathol Appl Neurobiol. 2002;28:292–300.PubMedCrossRef
114.
Gavins FNE, Dalli J, Flower RJ, Granger DN, Perretti M. Activation of the annexin 1 counter-regulatory circuit affords protection in the mouse brain microcirculation. FASEB J. 2007;21:1751–8.PubMedCrossRef
115.
Vital SA, Becker F, Holloway PM, Russell J, Perretti M, Granger DN, et al. Formyl-peptide receptor 2/3/lipoxin A4 receptor regulates neutrophil-platelet aggregation and attenuates cerebral inflammation: impact for therapy in cardiovascular disease. Circulation. 2016;133:2169–79.PubMedCrossRef
116.
Liu J-H, Feng D, Zhang Y-F, Shang Y, Wu Y, Li X-F, et al. Chloral hydrate preconditioning protects against ischemic stroke via upregulating annexin A1. CNS Neurosci Ther. 2015;21:718–26.PubMedCrossRef
117.
Joseph C, Buga A-M, Vintilescu R, Balseanu AT, Moldovan M, Junker H, et al. Prolonged gaseous hypothermia prevents the upregulation of phagocytosis-specific protein annexin 1 and causes low-amplitude EEG activity in the aged rat brain after cerebral ischemia. J Cereb Blood Flow Metab. 2012;32:1632–42.PubMedPubMedCentralCrossRef
118.
Gillies GE, McArthur S. Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines. Pharmacol Rev. 2010/04/16 ed. 2010;62:155–98.
119.
120.
Nadkarni S, McArthur S. Oestrogen and immunomodulation: new mechanisms that impact on peripheral and central immunity. Curr Opin Pharmacol. 2013;13:576–81.PubMedCrossRef
121.
Guo J, Krause DN, Horne J, Weiss JH, Li X, Duckles SP. Estrogen-receptor-mediated protection of cerebral endothelial cell viability and mitochondrial function after ischemic insult in vitro. J Cereb Blood Flow Metab. 2010;30:545–54.PubMedCrossRef
122.
Shin JA, Yoon JC, Kim M-S, Park E-M. Activation of classical estrogen receptor subtypes reduces tight junction disruption of brain endothelial cells under ischemia/reperfusion injury. Med: Free Radic Biol; 2016.
123.
Shin JA, Yang SJ, Jeong SI, Park HJ, Choi Y-H, Park E-M. Activation of estrogen receptor β reduces blood–brain barrier breakdown following ischemic injury. Neuroscience. 2013;235:165–73.PubMedCrossRef
124.
Tu J, Jufri NF. Estrogen signaling through estrogen receptor beta and G-protein-coupled estrogen receptor 1 in human cerebral vascular endothelial cells: implications for cerebral aneurysms. Biomed Res Int. 2013;2013:524324.PubMedPubMedCentral
125.
Burek M, Steinberg K, Förster CY. Mechanisms of transcriptional activation of the mouse claudin-5 promoter by estrogen receptor alpha and beta. Mol Cell Endocrinol. 2014;392:144–51.PubMedCrossRef
126.
Brailoiu E, Dun SL, Brailoiu GC, Mizuo K, Sklar LA, Oprea TI, et al. Distribution and characterization of estrogen receptor G protein-coupled receptor 30 in the rat central nervous system. J Endocrinol. 2007;193:311–21.PubMedCrossRef
127.
Razmara A, Sunday L, Stirone C, Wang XB, Krause DN, Duckles SP, et al. Mitochondrial effects of estrogen are mediated by estrogen receptor alpha in brain endothelial cells. J Pharmacol Exp Ther. 2008;325:782–90.PubMedPubMedCentralCrossRef
128.
Chen L-C, Lee W-S. Estradiol reduces ferrous citrate complex-induced NOS2 up-regulation in cerebral endothelial cells by interfering the nuclear factor kappa B transactivation through an estrogen receptor β-mediated pathway. PLoS ONE. 2013;8:e84320.PubMedPubMedCentralCrossRef
129.
Nathan L, Chaudhuri G. Antioxidant and prooxidant actions of estrogens: potential physiological and clinical implications. Semin Reprod Endocrinol. 1998;16:309–14.PubMedCrossRef
130.
Burek M, Arias-Loza PA, Roewer N, Förster CY. Claudin-5 as a novel estrogen target in vascular endothelium. Arterioscler Thromb Vasc Biol. 2010;30:298–304.PubMedCrossRef
131.
Kang HS, Ahn HS, Kang HJ, Gye MC. Effect of estrogen on the expression of occludin in ovariectomized mouse brain. Neurosci Lett. 2006;402:30–4.PubMedCrossRef
132.
Nourshargh S, Hordijk PL, Sixt M. Breaching multiple barriers: leukocyte motility through venular walls and the interstitium. Nat Rev Mol Cell Biol. 2010;11:366–78.PubMedCrossRef
133.
Nilsson B-O. Modulation of the inflammatory response by estrogens with focus on the endothelium and its interactions with leukocytes. Inflamm Res. 2007;56:269–73.PubMedCrossRef
134.
Hartz AMS, Madole EK, Miller DS, Bauer B. Estrogen receptor beta signaling through phosphatase and tensin homolog/phosphoinositide 3-kinase/Akt/glycogen synthase kinase 3 down-regulates blood–brain barrier breast cancer resistance protein. J Pharmacol Exp Ther. 2010;334:467–76.PubMedPubMedCentralCrossRef
135.
Hartz AMS, Mahringer A, Miller DS, Bauer B. 17-β-estradiol: a powerful modulator of blood–brain barrier BCRP activity. J Cereb Blood Flow Metab. 2010;30:1742–55.PubMedPubMedCentralCrossRef
136.
Mahringer A, Fricker G. BCRP at the blood–brain barrier: genomic regulation by 17β-estradiol. Mol Pharm. 2010;7:1835–47.PubMedCrossRef
137.
Hillman CH, Erickson KI, Kramer AF. Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci. 2008;9:58–65.PubMedCrossRef
138.
Raji CA, Ho AJ, Parikshak NN, Becker JT, Lopez OL, Kuller LH, et al. Brain structure and obesity. Hum Brain Mapp. 2010;31:353–64.PubMedPubMedCentral
139.
van Bloemendaal L, Ijzerman RG, Ten Kulve JS, Barkhof F, Diamant M, Veltman DJ, et al. Alterations in white matter volume and integrity in obesity and type 2 diabetes. Metab Brain Dis. 2016;31:621–9.PubMedPubMedCentralCrossRef
140.
Pannacciulli N, Del Parigi A, Chen K, Le DSNT, Reiman EM, Tataranni PA. Brain abnormalities in human obesity: a voxel-based morphometric study. Neuroimage. 2006;31:1419–25.PubMedCrossRef
141.
Tu Y-F, Tsai Y-S, Wang L-W, Wu H-C, Huang C-C, Ho C-J. Overweight worsens apoptosis, neuroinflammation and blood–brain barrier damage after hypoxic ischemia in neonatal brain through JNK hyperactivation. J. Neuroinflammation. 2011;8:40.PubMedPubMedCentralCrossRef
142.
Stranahan AM, Hao S, Dey A, Yu X, Baban B. Blood–brain barrier breakdown promotes macrophage infiltration and cognitive impairment in leptin receptor-deficient mice. Blood Flow Metab: J. Cereb; 2016.
143.
Davidson TL, Monnot A, Neal AU, Martin AA, Horton JJ, Zheng W. The effects of a high-energy diet on hippocampal-dependent discrimination performance and blood–brain barrier integrity differ for diet-induced obese and diet-resistant rats. Physiol Behav. 2012;107:26–33.PubMedPubMedCentralCrossRef
144.
Deng J, Zhang J, Feng C, Xiong L, Zuo Z. Critical role of matrix metalloprotease-9 in chronic high fat diet-induced cerebral vascular remodelling and increase of ischaemic brain injury in mice. Cardiovasc Res. 2014;103:473–84.PubMedPubMedCentralCrossRef
145.
Tucsek Z, Toth P, Sosnowska D, Gautam T, Mitschelen M, Koller A, et al. Obesity in aging exacerbates blood–brain barrier disruption, neuroinflammation, and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer’s disease. J Gerontol Ser A. 2014;69:1212–26.CrossRef
146.
Kim DW, Glendining KA, Grattan DR, Jasoni CL. Maternal obesity in the mouse compromises the blood–brain barrier in the arcuate nucleus of offspring. Endocrinology. 2016;157:2229–42.PubMedCrossRef
147.
Buckman LB, Thompson MM, Moreno HN, Ellacott KLJ. Regional astrogliosis in the mouse hypothalamus in response to obesity. J Comp Neurol. 2013;521:1322–33.PubMedPubMedCentralCrossRef
148.
Ouyang S, Hsuchou H, Kastin AJ, Wang Y, Yu C, Pan W. Diet-induced obesity suppresses expression of many proteins at the blood–brain barrier. J Cereb Blood Flow Metab. 2013;34:1–9.
149.
Kanoski SE, Zhang Y, Zheng W, Davidson TL. The effects of a high-energy diet on hippocampal function and blood–brain barrier integrity in the rat. J Alzheimer’s Dis. 2010;21:207–19.
150.
McColl BW, Rose N, Robson FH, Rothwell NJ, Lawrence CB. Increased brain microvascular MMP-9 and incidence of haemorrhagic transformation in obese mice after experimental stroke. J Cereb Blood Flow Metab. 2010;30:267–72.PubMedCrossRef
151.
Maysami S, Haley MJ, Gorenkova N, Krishnan S, McColl BW, Lawrence CB. Prolonged diet-induced obesity in mice modifies the inflammatory response and leads to worse outcome after stroke. J Neuroinflam. 2015;12:140.CrossRef
152.
Parimisetty A, Dorsemans A-C, Awada R, Ravanan P, Diotel N, Lefebvre d’Hellencourt C. Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research. J Neuroinflam. 2016;13:67.CrossRef
153.
154.
Kosicka A, Cunliffe AD, Mackenzie R, Zariwala MG, Perretti M, Flower RJ, et al. Attenuation of plasma annexin A1 in human obesity. FASEB J. 2013;27:368–78.PubMedCrossRef
155.
Kim H, Kang H, Heo RW, Jeon BT, Yi C, Shin HJ, et al. Caloric restriction improves diabetes-induced cognitive deficits by attenuating neurogranin-associated calcium signaling in high-fat diet-fed mice. J Cereb Blood Flow Metab. 2016;36:1098–110.PubMedCrossRef
156.
Wang H, Chen F, Zhong KL, Tang SS, Hu M, Long Y, et al. PPARγ agonists regulate bidirectional transport of amyloid-β across the blood–brain barrier and hippocampus plasticity in db/db mice. Br J Pharmacol. 2016;173:372–85.PubMedCrossRef
157.
Moran C, Phan TG, Chen J, Blizzard L, Beare R, Venn A, et al. Brain atrophy in type 2 diabetes: regional distribution and influence on cognition. Diabetes Care. 2013;36:4036–42.PubMedPubMedCentralCrossRef
158.
Hoogenboom WS, Marder TJ, Flores VL, Huisman S, Eaton HP, Schneiderman JS, et al. Cerebral white matter integrity and resting-state functional connectivity in middle-aged patients with type 2 diabetes. Diabetes. 2014;63:728–38.PubMedPubMedCentralCrossRef
159.
Van Duinkerken E, Schoonheim MM, Ijzerman RG, Klein M, Ryan CM, Moll AC, et al. Diffusion tensor imaging in type 1 diabetes: decreased white matter integrity relates to cognitive functions. Diabetologia. 2012;55:1218–20.PubMedPubMedCentralCrossRef
160.
Roberts RO, Knopman DS, Przybelski SA, Mielke MM, Kantarci K, Preboske GM, et al. Association of type 2 diabetes with brain atrophy and cognitive impairment. Neurology. 2014;82:1132–41.PubMedPubMedCentralCrossRef
161.
Cheng G, Huang C, Deng H, Wang H. Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies. Intern Med J. 2012;42:484–91.PubMedCrossRef
162.
Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders. Biol Psychiatry. 2010;67:505–12.PubMedCrossRef
163.
Saczynski JS, Siggurdsson S, Jonsson PV, Eiriksdottir G, Olafsdottir E, Kjartansson O, et al. Glycemic status and brain injury in older individuals: the age gene/environment susceptibility-Reykjavik study. Diabetes Care. 2009;32:1608–13.PubMedPubMedCentralCrossRef
164.
Mitchell AB, Cole JW, McArdle PF, Cheng Y-C, Ryan KA, Sparks MJ, et al. Obesity increases risk of ischemic stroke in young adults. Stroke. 2015;46:1690–2.PubMedPubMedCentralCrossRef
165.
Pietrani NT, Ferreira CN, Rodrigues KF, Bosco AA, Oliveira MC, Teixeira AL, et al. Annexin A1 concentrations is decreased in patients with diabetes type 2 and nephropathy. Clin Chim Acta. 2014;436:181–2.PubMedCrossRef
166.
Price TO, Eranki V, Banks WA, Ercal N, Shah GN. Topiramate treatment protects blood–brain barrier pericytes from hyperglycemia-induced oxidative damage in diabetic mice. Endocrinology. 2012;153:362–72.PubMedCrossRef
167.
Hu P, Thinschmidt JS, Yan Y, Hazra S, Bhatwadekar A, Caballero S, et al. CNS inflammation and bone marrow neuropathy in type 1 diabetes. Am J Pathol. 2013;183:1608–20.PubMedPubMedCentralCrossRef
168.
Luo Y, Kaur C, Ling EA. Neuronal and glial response in the rat hypothalamus-neurohypophysis complex with streptozotocin-induced diabetes. Brain Res. 2002;925:42–54.PubMedCrossRef
169.
Jing YH, Chen KH, Kuo PC, Pao CC, Chen JK. Neurodegeneration in streptozotocin-induced diabetic rats is attenuated by treatment with resveratrol. Neuroendocrinology. 2013;98:116–27.PubMedCrossRef
170.
Yoo DY, Yim HS, Jung HY, Nam SM, Kim JW, Choi JH, et al. Chronic type 2 diabetes reduces the integrity of the blood–brain barrier by reducing tight junction proteins in the hippocampus. Sci: J Vet Med; 2016.
171.
Hawkins BT, Lundeen TF, Norwood KM, Brooks HL, Egleton RD. Increased blood–brain barrier permeability and altered tight junctions in experimental diabetes in the rat: contribution of hyperglycaemia and matrix metalloproteinases. Diabetologia. 2007;50:202–11.PubMedCrossRef
172.
Zanotto C, Simão F, Gasparin MS, Biasibetti R, Tortorelli LS, Nardin P, et al. Exendin-4 reverses biochemical and functional alterations in the blood–brain and blood-CSF barriers in diabetic rats. Mol Neurobiol. 2016;1–13.
173.
Thrailkill KM, Bunn RC, Moreau CS, Cockrell GE, Simpson PM, Coleman HN, et al. Matrix metalloproteinase-2 dysregulation in type 1 diabetes. Diabetes Care. 2007;30:2321–6.PubMedPubMedCentralCrossRef
174.
Harris AK, Hutchinson JR, Sachidanandam K, Johnson MH, Dorrance AM, Stepp DW, et al. Type 2 diabetes causes remodeling of cerebrovasculature via differential regulation of matrix metalloproteinases and collagen synthesis: role of endothelin-1. Diabetes. 2005;54:2638–44.PubMedCrossRef
175.
Shao B, Bayraktutan U. Hyperglycaemia promotes human brain microvascular endothelial cell apoptosis via induction of protein kinase C-βI and prooxidant enzyme NADPH oxidase. Redox Biol. 2014;2:694–701.PubMedPubMedCentralCrossRef
176.
Shimizu F, Sano Y, Tominaga O, Maeda T, Abe MA, Kanda T. Advanced glycation end-products disrupt the blood–brain barrier by stimulating the release of transforming growth factor-β by pericytes and vascular endothelial growth factor and matrix metalloproteinase-2 by endothelial cells in vitro. Neurobiol Aging. 2013;34:1902–12.PubMedCrossRef
177.
Aggarwal A, Khera A, Singh I, Sandhir R. S-nitrosoglutathione prevents blood–brain barrier disruption associated with increased matrix metalloproteinase-9 activity in experimental diabetes. J Neurochem. 2015;132:595–608.PubMed
178.
Kang H, Ko J, Jang S-W. The role of annexin A1 in expression of matrix metalloproteinase-9 and invasion of breast cancer cells. Biochem Biophys Res Commun. 2012;423:188–94.PubMedCrossRef
179.
Tagoe CE, Marjanovic N, Park JY, Chan ES, Abeles AM, Attur M, et al. Annexin-1 mediates TNF-alpha-stimulated matrix metalloproteinase secretion from rheumatoid arthritis synovial fibroblasts. J Immunol. 2008;181:2813–20.PubMedCrossRef
180.
Liu Q-H, Shi M-L, Bai J, Zheng J-N. Identification of ANXA1 as a lymphatic metastasis and poor prognostic factor in pancreatic ductal adenocarcinoma. Asian Pac J Cancer Prev. 2015;16:2719–24.PubMedCrossRef
181.
Ghitescu LD, Gugliucci A, Dumas F. Actin and annexins I and II are among the main endothelial plasmalemma-associated proteins forming early glucose adducts in experimental diabetes. Diabetes. 2001;50:1666–74.PubMedCrossRef
182.
van Harten B, de Leeuw F-E, Weinstein HC, Scheltens P, Biessels GJ. Brain imaging in patients with diabetes: a systematic review. Diabetes Care. 2006;29:2539–48.PubMedCrossRef
183.
Doubal FN, MacGillivray TJ, Patton N, Dhillon B, Dennis MS, Wardlaw JM. Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke. Neurology. 2010;74:1102–7.PubMedPubMedCentralCrossRef
184.
Smith HK, Gil CD, Oliani SM, Gavins FNE. Targeting formyl peptide receptor 2 reduces leukocyte-endothelial interactions in a murine model of stroke. FASEB J. 2015;29:2161–71.PubMedCrossRef
185.
Cooray SN, Gobbetti T, Montero-Melendez T, McArthur S, Thompson D, Clark AJL, et al. Ligand-specific conformational change of the G-protein-coupled receptor ALX/FPR2 determines proresolving functional responses. Proc Natl Acad Sci USA. 2013;110:18232–7.PubMedPubMedCentralCrossRef
186.
Headland SE, Jones HR, Norling LV, Kim A, Souza PR, Corsiero E, et al. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Sci Transl Med. 2015;7:315ra190.PubMedCrossRef
187.
Fredman G, Kamaly N, Spolitu S, Milton J, Ghorpade D, Chiasson R, et al. Targeted nanoparticles containing the proresolving peptide Ac2–26 protect against advanced atherosclerosis in hypercholesterolemic mice. Sci Transl Med. 2015;7:275ra20.PubMedPubMedCentralCrossRef
Metadata
Title
The restorative role of annexin A1 at the blood–brain barrier
Authors
Simon McArthur
Rodrigo Azevedo Loiola
Elisa Maggioli
Mariella Errede
Daniela Virgintino
Egle Solito
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2016
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-016-0043-0

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