The role of the blood brain barrier in neurodegenerative disorders and their treatment

Journal of Alzheimer's Disease

Volumn 24, Issue 4, 2011, Pages 643-656

  Palmer, Alan M ^a  

^a MS Therapeutics Ltd   (United Kingdom)

Author keywords

Blood brain barrier; brain injuries; drug discovery; neurodegeneration; neuroinflammation; neurological disorders; neuroprotection; therapeutics

Indexed keywords

BETA1A INTERFERON; CLADRIBINE; EXCITATORY AMINO ACID; EXCITOTOXIN; FINGOLIMOD; FUMARIC ACID DIMETHYL ESTER; GLATIRAMER; INTERFERON BETA SERINE; LAQUINIMOD; NATALIZUMAB; NEUROPROTECTIVE AGENT; TERIFLUNOMIDE;

ACTIVE TRANSPORT; AGED; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; BLOOD BRAIN BARRIER; BRAIN INFECTION; BRAIN INJURY; BRAIN TUMOR; CELL LINE; CHEMICAL INTERACTION; CHRONIC DISEASE; CONCENTRATION (PARAMETERS); CREUTZFELDT JAKOB DISEASE; DEGENERATIVE DISEASE; DEMENTIA; DISEASE COURSE; DISEASE SEVERITY; DRUG DEVELOPMENT; ENDOCYTOSIS; ENDOTHELIUM CELL; EX VIVO STUDY; FRONTOTEMPORAL DEMENTIA; HUMAN; HUNTINGTON CHOREA; IMMUNOCOMPETENT CELL; IN VITRO STUDY; IN VIVO STUDY; INTERSTITIAL FLUID; LEWY BODY; MOLECULAR MODEL; MULTIINFARCT DEMENTIA; MULTIPLE SCLEROSIS; NONHUMAN; PARKINSON DISEASE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; RESEARCH; REVIEW; STROKE; TRAUMATIC BRAIN INJURY;

EID: 79959190762     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-2011-110368     Document Type: Review

References (88)

1. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ (2010) Structure and function of the blood-brain barrier. Neurobiol Dis 37, 13-25.
2. Alavijeh MS, Chishty M, Qaiser MZ, PalmerAM(2005) Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. NeuroRx 2, 554-571. (Pubitemid 41393265)
3. Bhattacharya R (2010) Alzheimers unlocked. New Scientist 207, 42-45.
4. Beal MF (2007) Mitochondria and neurodegeneration. Novartis Found Symp 287, 183-192.
5. Szydlowska K, Tymianski M (2010) Calcium, ischemia and excitotoxicity. Cell Calcium 47, 122-129.
6. Martin LJ (2010) Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases. Pharmaceuticals (Basel) 3, 839-915.
7. Palmer AM (2010) The role of the blood-CNS barrier in CNS disorders and their treatment. Neurobiol Dis 37, 3-12.
8. BanksWA, Erickson MA (2010) The blood-brain barrier and immune function and dysfunction. Neurobiol Dis 37, 26-32.
9. Palmer AM (2011) Neuroprotective therapeutics for Alzheimers disease: progress and prospects. Trends Pharmacol Sci 32 141-147.
10. Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E (2011) Alzheimers disease. Lancet 377, 1019-1031.
11. Bekris LM, Yu CE, Bird TD, Tsuang DW(2010) Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol 23, 213-227.
12. Ince PG, Fernando MS (2003) Neuropathology of vascular cognitive impairment and vascular dementia. Int Psychogeriatr 15 Suppl 1, 71-75. (Pubitemid 37175170)
13. Guidetti D, Casali B, Mazzei RL, Dotti MT (2006) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Clin Exp Hypertens 28, 271-277. (Pubitemid 44178499)
14. Jellinger KA, Attems J (2007) Neuropathological evaluation of mixed dementia. J Neurol Sci 257, 80-87. (Pubitemid 46856518)
15. Burn DJ (2006) Cortical Lewy body disease and Parkinsons disease dementia. Curr Opin Neurol 19, 572-579. (Pubitemid 44760441)
16. Lee VM, Trojanowski JQ (2006) Mechanisms of Parkinsons disease linked to pathological alpha-synuclein: new targets for drug discovery. Neuron 52, 33-38. (Pubitemid 44479831)
17. Hardy J (2010) Genetic analysis of pathways to Parkinson disease. Neuron 68, 201-206.
18. Neary D, Snowden J, Mann D (2005) Frontotemporal dementia. Lancet Neurol 4, 771-780. (Pubitemid 41457293)
19. Rabinovici GD, Miller BL (2010) Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs 24, 375-398.
20. Wadsworth JD, Collinge J (2007) Update on human prion disease. Biochim Biophys Acta 1772, 598-609. (Pubitemid 46887654)
21. Forstl H, Haass C, Hemmer B, Meyer B, Halle M (2010) Boxing-acute complications and late sequelae: from concussion to dementia. Dtsch Arztebl Int 107, 835-839.
22. Hulse GK, Lautenschlager NT, Tait RJ, Almeida OP (2005) Dementia associated with alcohol and other drug use. Int Psychogeriatr 17 Suppl 1, S109-S127. (Pubitemid 44561759)
23. Lees AJ, Hardy J, Revesz T (2009) Parkinsons disease. Lancet 373, 2055-2066.
24. Shulman JM, De Jager PL, Feany MB (2010) Parkinsons Disease: Genetics and Pathogenesis. Annu Rev Pathol 6, 193-222
25. Ferrari R, Kapogiannis D, Huey ED, Momeni P (2011) FTD and ALS: A Tale of Two Diseases. Curr Alzheimer Res, in press.
26. Ince PG, Codd GA (2005) Return of the cycad hypothesis -does the amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) of Guam have new implications for global health? Neuropathol Appl Neurobiol 31, 345-353. (Pubitemid 41059855)
27. Rao SD, Banack SA, Cox PA, Weiss JH (2006) BMAA selectively injures motor neurons via AMPA/kainate receptor activation. Exp Neurol 201, 244-252. (Pubitemid 44226467)
28. Canton T, Bohme GA, Boireau A, Bordier F, Mignani S, Jimonet P, Jahn G, Alavijeh M, Stygall J, Roberts S, BrealeyC, Vuilhorgne M, DebonoMW, Le Guern S, Laville M, Briet D, Roux M, Stutzmann JM, Pratt J (2001) RPR 119990, a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist: synthesis, pharmacological properties, and activity in an animal model of amyotrophic lateral sclerosis. J Pharmacol Exp Ther 299, 314-322. (Pubitemid 32905149)
29. Ross CA, Tabrizi SJ (2011) Huntingtons disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 10, 83-98.
30. Donnan GA, Fisher M, Macleod M, Davis SM (2008) Stroke. Lancet 371, 1612-1623. (Pubitemid 351626845)
31. Ghajar J (2000) Traumatic brain injury. Lancet 356, 923-929.
32. Bruns J Jr, HauserWA (2003) The epidemiology of traumatic brain injury: a review. Epilepsia 44 Suppl 10, 2-10. (Pubitemid 37280386)
33. Compston A, Coles A (2008) Multiple sclerosis. Lancet 372, 1502-1517.
34. PandeyK, Lublin FD (2009) Clinically isolated syndrome and multiple sclerosis: rethinking the arsenal. Curr Treat Options Neurol 11, 193-202.
35. Fisniku LK, Brex PA, Altmann DR, Miszkiel KA, Benton CE, Lanyon R, Thompson AJ, Miller DH (2008) Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 131, 808-817. (Pubitemid 351294716)
36. Palmer AM (2009) Pharmacotherapy for multiple sclerosis: progress and prospects. Curr Opin Investig Drugs 10, 407-417.
37. Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, Edan G (2010) Evidence for a two-stage dis ability progression in multiple sclerosis. Brain 133(Pt 7), 1900-1913
38. Ginsberg MD (2008) Neuroprotection for ischemic stroke: past, present and future. Neuropharmacology 55, 363-389.
39. Jain KK (2008) Neuroprotection in traumatic brain injury. Drug Discov Today 13, 1082-1089.
40. Lau A, Tymianski M (2010) Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch 460, 525-542.
41. Dawson DA, Wadsworth G, Palmer AM (2001) A comparative assessment of the efficacy and side-effect liability of neuroprotective compounds in experimental stroke. Brain Res 892, 344-350. (Pubitemid 32141221)
42. Mehta SL, Manhas N, Raghubir R (2007) Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev 54, 34-66. (Pubitemid 46498164)
43. PalmerAM(2010) Teriflunomide, an inhibitor of dihydroorotate dehydrogenase for the potential oral treatment of multiple sclerosis. Curr Opin Investig Drugs 11, 1313-1323.
44. Hartung HP, Aktas O (2010) Oral therapies for multiple sclerosis: are we there yet? Lancet Neurol 9, 454-457.
45. Marriott JJ, OConnor PW (2010) Emerging Therapies in Relapsing-Remitting Multiple Sclerosis. Rev Recent Clin Trials 5, 179-188
46. Gasperini C, Cefaro LA, Borriello G, Tosto G, Prosperini L, Pozzilli C (2008) Emerging oral drugs for multiple sclerosis. Expert Opin Emerg Drugs 13, 465-477.
47. Filippini G, Munari L, Incorvaia B, Ebers GC, Polman C, DAmico R, RiceGP(2003) Interferons in relapsing remitting multiple sclerosis: a systematic review. Lancet 361, 545-552. (Pubitemid 36207471)
48. Gaillard PJ, de Boer AB, Breimer DD (2003) Pharmacological investigations on lipopolysaccharide-induced permeability changes in the blood-brain barrier in vitro. Microvasc Res 65, 24-31. (Pubitemid 36263287)
49. Carvey PM, Hendey B, Monahan AJ (2009) The blood-brain barrier in neurodegenerative disease: a rhetorical perspective. J Neurochem 111, 291-314.
50. Neumann H, Medana IM, Bauer J, Lassmann H (2002) Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases. Trends Neurosci 25, 313-319. (Pubitemid 34667013)
51. Pino P, Taoufiq Z, Nitcheu J, Vouldoukis I, Mazier D (2005) Blood-brain barrier breakdown during cerebral malaria: suicide or murder? Thromb Haemost 94, 336-340. (Pubitemid 41122488)
52. Toborek M, Lee YW, Flora G, Pu H, Andras IE, Wylegala E, Hennig B, Nath A (2005) Mechanisms of the blood-brain barrier disruption in HIV-1 infection. Cell Mol Neurobiol 25, 181-199. (Pubitemid 40558590)
53. Minagar A, Alexander JS (2003) Blood-brain barrier disruption in multiple sclerosis. Mult Scler 9, 540-549. (Pubitemid 37479401)
54. Engelhardt B, Kappos L (2008) Natalizumab: targeting alpha4-integrins in multiple sclerosis. Neurodegener Dis 5, 16-22. (Pubitemid 350261811)
55. Polman CH, OConnor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354, 899-910.
56. Stoll G, Bendszus M (2009) Imaging of inflammation in the peripheral and central nervous system by magnetic resonance imaging. Neuroscience 158, 1151-1160.
57. Vos CM, Geurts JJ, Montagne L, van Haastert ES, Bo L, van der Valk P, Barkhof F, de Vries HE (2005) Blood-brain barrier alterations in both focal and diffuse abnormalities on postmortem MRI in multiple sclerosis. Neurobiol Dis 20, 953-960. (Pubitemid 41619370)
58. Soon D, Tozer DJ, Altmann DR, Tofts PS, Miller DH (2007) Quantification of subtle blood-brain barrier disruption in nonenhancing lesions in multiple sclerosis: a study of disease and lesion subtypes. Mult Scler 13, 884-894. (Pubitemid 351540860)
59. Sandoval KE,Witt KA (2008) Blood-brain barrier tight junction permeability and ischemic stroke. Neurobiol Dis 32, 200-219.
60. Tomas-Camardiel M, Venero JL, Herrera AJ, De Pablos RM, Pintor-Toro JA, Machado A, Cano J (2005) Blood-brain barrier disruption highly induces aquaporin-4mRNAand protein in perivascular and parenchymal astrocytes: protective effect by estradiol treatment in ovariectomized animals. J Neurosci Res 80, 235-246. (Pubitemid 40676307)
61. Habgood MD, Bye N, Dziegielewska KM, Ek CJ, Lane MA, Potter A, Morganti-Kossmann C, Saunders NR (2007) Changes in blood-brain barrier permeability to large and small molecules following traumatic brain injury in mice. Eur J Neurosci 25, 231-238. (Pubitemid 46096237)
62. CornfordEM,HymanS, Black KL, CornfordME,VintersHV, Pardridge WM (1995) High expression of the Glut1 glucose transporter in human brain hemangioblastoma endothelium. J Neuropathol Exp Neurol 54, 842-851.
63. Cornford EM, Hyman S, Cornford ME, Landaw EM, Delgado-EscuetaAV(1998) Interictal seizure resections show two configurations of endothelial Glut1 glucose transporter in the human blood-brain barrier. J Cereb Blood Flow Metab 18, 26-42. (Pubitemid 28019009)
64. Rogers J (2008) The inflammatory response in Alzheimers disease. J Periodontol 79, 1535-1543.
65. Kalaria RN (1999) The blood-brain barrier and cerebrovascular pathology in Alzheimers disease. Ann N Y Acad Sci 893, 113-125. (Pubitemid 30038071)
66. Garbuzova-Davis S, Saporta S, Sanberg PR (2008) Implications of blood-brain barrier disruption in ALS. Amyotroph Lateral Scler 9, 375-376.
67. Stolp HB, Dziegielewska KM (2009) Review: Role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases. Neuropathol Appl Neurobiol 35, 132-146.
68. Bartels AL,WillemsenAT,Kortekaas R, de JongBM,de Vries R, de Klerk O, van Oostrom JC, Portman A, Leenders KL (2008) Decreased blood-brain barrier P-glycoprotein function in the progression of Parkinsons disease, PSP and MSA. J Neural Transm 115, 1001-1009.
69. Smith PF (2008) Inflammation in Parkinsons disease: an update. Curr Opin Investig Drugs 9, 478-484.
70. Papadopoulos MC, Saadoun S, Binder DK, Manley GT, Krishna S, Verkman AS (2004) Molecular mechanisms of brain tumor edema. Neuroscience 129, 1011-1020. (Pubitemid 39556252)
71. Schor NF (2009) Pharmacotherapy for adults with tumors of the central nervous system. Pharmacol Ther 121, 253-264.
72. Blakeley J (2008) Drug delivery to brain tumors. Curr Neurol Neurosci Rep 8, 235-241.
73. Jeffrey P, Summerfield S (2010) Assessment of the bloodbrain barrier in CNS drug discovery. Neurobiol Dis 37, 33-37.
74. Vastag M, Keseru GM (2009) Current in vitro and in silico models of blood-brain barrier penetration: a practical view. Curr Opin Drug Discov Devel 12, 115-124.
75. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW (2002) Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther 303, 1029-1037. (Pubitemid 35424386)
76. Wang Q, Rager JD, Weinstein K, Kardos PS, Dobson GL, Li J, Hidalgo IJ (2005) Evaluation of the MDR-MDCK cell line as a permeability screen for the blood-brain barrier. Int J Pharm 288, 349-359. (Pubitemid 40038588)
77. Jeffrey P, Summerfield SG (2007) Challenges for blood-brain barrier (BBB) screening. Xenobiotica 37, 1135-1151. (Pubitemid 350041554)
78. Friden M, Gupta A, Antonsson M, BredbergU, Hammarlund-Udenaes M (2007) In vitro methods for estimating unbound drug concentrations in the brain interstitial and intracellular fluids. Drug Metab Dispos 35, 1711-1719. (Pubitemid 47296068)
79. Summerfield SG, Lucas AJ, Porter RA, Jeffrey P, Gunn RN, Read KR, Stevens AJ, Metcalf AC, Osuna MC, Kilford PJ, Passchier J, Ruffo AD (2008) Toward an improved prediction of human in vivo brain penetration. Xenobiotica 38, 1518-1535.
80. Alavijeh MS, Palmer AM (2010) Measurement of the pharmacokinetics and pharmacodynamics of neuroactive compounds. Neurobiol Dis 37, 38-47.
81. de Lange EC, Ravenstijn PG, Groenendaal D, van Steeg TJ (2005) Toward the prediction of CNS drug-effect profiles in physiological and pathological conditions using microdialysis and mechanism-based pharmacokinetic- pharmacodynamic modeling. AAPS J 7, E532-E543.
82. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46, 3-26. (Pubitemid 33653411)
83. Mehdipour AR, Hamidi M (2009) Brain drug targeting: a computational approach for overcoming blood-brain barrier. Drug Discov Today 14, 1030-1036.
84. Rodemer C, Haucke V (2008) Clathrin/AP-2-dependent endocytosis: a novel playground for the pharmacological toolbox? Handb Exp Pharmacol, 105-122.
85. Zhou SF (2008) Structure, function and regulation of Pglycoprotein and its clinical relevance in drug disposition. Xenobiotica 38, 802-832.
86. Demel MA, Kramer O, Ettmayer P, Haaksma EE, Ecker GF (2009) Predicting ligand interactions with ABC transporters in ADME. Chem Biodivers 6, 1960-1969.
87. Pun PB, Lu J, Moochhala S (2009) Involvement of ROS in BBB dysfunction. Free Radic Res 43, 348-364.
88. Lull ME, Block ML (2010) Microglial activation and chronic neurodegeneration. Neurotherapeutics 7, 354-365.