Astrocytic modulation of blood brain barrier: Perspectives on Parkinson's disease

Frontiers in Cellular Neuroscience

Volumn 8, Issue AUG, 2014, Pages

  Cabezas, Ricardo ^a   Ávila, Marcos ^a   Gonzalez, Janneth ^a   El Bachá, Ramon Santos ^b   Báez, Eliana ^a   García Segura, Luis Miguel ^c   Coronel, Juan Camilo Jurado ^a   Capani, Francisco ^d   Cardona Gomez, Gloria Patricia ^e   Barreto, George E ^a  

^a PONTIFICIA UNIVERSIDAD JAVERIANA   (Colombia)

^b FEDERAL UNIVERSITY OF BAHIA   (Brazil)

^c INSTITUTO CAJAL   (Spain)

^d Facultad de Ciencias Naturales e Instituto M Lillo   (Argentina)

^e UNIVERSIDAD DE ANTIOQUIA   (Colombia)

Author keywords

Astrocytes; BBB; Endothelial cells; Parkinson disease; Reactive astrogliosis

Indexed keywords

ALPHA SYNUCLEIN; BRAIN DERIVED NEUROTROPHIC FACTOR; FIBROBLAST GROWTH FACTOR; INTERLEUKIN 1BETA; INTERLEUKIN 6; MATRIX METALLOPROTEINASE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NESTIN; PLATELET DERIVED GROWTH FACTOR; SOMATOMEDIN; TENASCIN; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN; VIMENTIN;

ANGIOGENESIS; ASTROCYTE; ASTROCYTOSIS; BLOOD BRAIN BARRIER; CELL DISRUPTION; CELL MEMBRANE PERMEABILITY; CELL SURVIVAL; DYSKINESIA; EMBRYO DEVELOPMENT; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; HOMEOSTASIS; HUMAN; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PERICYTE; POSITRON EMISSION TOMOGRAPHY; PROTEIN EXPRESSION; REVIEW; TIGHT JUNCTION;

EID: 84905447142     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2014.00211     Document Type: Review

References (143)

1. Abbott, N. J., Rönnbäck, L., and Hansson, E. (2006). Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 7, 41-53. doi: 10. 1038/nrn1824
2. Aberg, N. D., Brywe, K. G., and Isgaard, J. (2006). Aspects of growth hormone and insulin-like growthfactor-I related to neuroprotection, regeneration and functional plasticity in the adult brain. Sci. World J. 6, 53-80. doi: 10. 1100/tsw. 2006. 22
3. Adelson, J. D., Barreto, G. E., Xu, L., Kim, T., Brott, B. K., and Ouyang, Y. B. (2012). Neuroprotection from stroke in the absence of MHCI or PirB. Neuron 73, 1100-1107. doi: 10. 1016/j. neuron. 2012. 01. 020
4. Agarwal, R., and Shukla, G. S. (1999). Potential role of cerebral glutathione in the maintenance of blood-brain barrier integrity in rat. Neurochem. Res. 24, 1507-1514. doi: 10. 1023/A:1021191729865
5. Allen, S. J., Watson, J. J., Shoemark, D. K., Barua, N. U., and Patel, N. K. (2013). GDNF, NGF, and BDNF as therapeutic options for neurodegeneration. Pharmacol. Ther. 138, 155-175. doi: 10. 1016/j. pharmthera. 2013. 01. 004
6. Alvarez, J. I., Katayama, T., and Prat, A. (2013). Glial influence on the blood brain barrier. Glia 61, 1939-1958. doi: 10. 1002/glia. 22575
7. Anderson, C. M., and Swanson, R. A. (2000). Astrocyte glutamate transport: review of properties, regulation and physiological functions. Glia 32, 1-14. doi: 10. 1002/1098-1136(200010)32:1<1::aid-glia10>3. 3. co;2-n
8. Annese, V., Herrero, M. T., Di Pentima, M., Gomez, A., Lombardi, L., Ros, C. M., et al. (2014). Metalloproteinase 9 contributes toinflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced Parkinsonism. Brain Struct. Funct. doi: 10. 1007/s00429-014-0718-8. [Epub ahead of print].
9. Armulik, A., Genové, G., Mäe, M., Nisancioglu, M. H., Wallgard, E., Niaudet, C., et al. (2010). Pericytes regulate the blood-brain barrier. Nature 468, 557-561. doi: 10. 1038/nature09522
10. Bambrick, L., Kristian, T., and Fiskum, G. (2004). Astrocyte mitochondrial mechanisms of ischemic brain injury and neuroprotection. Neurochem. Res. 29, 601-608. doi: 10. 1023/b:nere. 0000014830. 06376. e6
11. Barreto, G. E., Gonzalez, J., Torres, Y., and Morales, L. (2011). Astrocytic-neuronal crosstalk: implications for neuroprotection from brain injury. Neurosci. Res. 71, 107-113. doi: 10. 1016/j. neures. 2011. 06. 004
12. Barreto, G., Santos-Galindo, M., Diz-Chaves, Y., Pernía, O., Carrero, P., Azcoitia, I., et al. (2009). Selective estrogen receptor modulators decrease reactive astrogliosis in the injured brain: effects of aging and prolonged depletion of ovarian hormones. Endocrinology 150, 5010-5015. doi: 10. 1210/en. 2009-0352
13. Barreto, G. E., White, R. E., Xu, L., Palm, C. J., and Giffard, R. G. (2012). Effects of heat shock protein 72 (Hsp72) on evolution of astrocyte activation following stroke in the mouse. Exp. Neurol. 238, 284-296. doi: 10. 1016/j. expneurol. 2012. 08. 015
14. Barreto, G., Veiga, S., Azcoitia, I., Garcia-Segura, L. M., and Garcia-Ovejero, D. (2007). Testosterone decreases reactive astroglia and reactive microglia after brain injury in male rats: role of its metabolites, oestradiol and dihydrotestosterone. Eur. J. Neurosci. 25, 3039-3046. doi: 10. 1111/j. 1460-9568. 2007. 05563. x
15. Bartels, A. L. (2011). Blood-brain barrier P-glycoprotein function in neurodegenerative disease. Curr. Pharm. Des. 17, 2771-2777. doi: 10. 2174/138161211797440122
16. Bartels, A. L., Willemsen, A. T., Kortekaas, R., de Jong, B. M., de Vries, R., de Klerk, O., et al. (2008). Decreased blood-brain barrier P-glycoprotein function in the progression of Parkinson's disease, PSP and MSA. J. Neural Transm. 115, 1001-1009. doi: 10. 1007/s00702-008-0030-y
17. Baxendale, S. A., Van Paesschen, W., Thompson, P. J., Duncan, J. S., Harkness, W. F., and Shorvon, S. D. (1998). Hippocampal cell loss and gliosis: relationship to preoperative and postoperative memory function. Neuropsychiatry Neuropsychol. Behav. Neurol. 11, 12-21.
18. Bergers, G., and Song, S. (2005). The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol. 7, 452-464. doi: 10. 1215/s1152851705000232
19. Betarbet, R., Sherer, T. B., MacKenzie, G., Garcia-Osuna, M., Panov, A. V., and Greenamyre, J. T. (2000). Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosci. 3, 1301-1306. doi: 10. 1038/81834
20. Blackburn, D., Sargsyan, S., Monk, P. N., and Shaw, P. J. (2009). Astrocyte function and role in motor neuron disease: a future therapeutic target? Glia 57, 1251-1264. doi: 10. 1002/glia. 20848
21. Bonkowski, D., Katyshev, V., Balabanov, R. D., Borisov, A., and Dore-Duffy, P. (2011). The CNS microvascular pericyte: pericyte-astrocyte crosstalk in the regulation of tissue survival. Fluids Barriers CNS 8:8. doi: 10. 1186/2045-8118-8-8
22. Botella, J. A., Bayersdorfe, F., and Schneuwly, S. (2008). Superoxide dismutase overexpression protects dopaminergic neurons in a Drosophila model of Parkinson's disease. Neurobiol. Dis. 30, 65-73. doi: 10. 1016/j. nbd. 2007. 11. 013
23. Braak, H., de Vos, R. A., Bohl, J., and Del Tredici, K. (2006). Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci. Lett. 396, 67-72. doi: 10. 1016/j. neulet. 2005. 11. 012
24. Brown, T. P., Rumsby, P. C., Capleton, A. C., Rushton, L., and Levy, L. S. (2006). Pesticides and Parkinson's disease-is there a link? Environ. Health Perspect. 114, 156-164. doi: 10. 1289/ehp. 8095
25. Bushong, E. A., Martone, M. E., Jones, Y. Z., and Ellisman, M. H. (2002). Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J. Neurosci. 22, 183-192.
26. Carvey, P. M. C. H., Zhao, B., Hendey, H., Lum, J., Trachtenberg, B. S., Desai, J., et al. (2005). 6-Hydroxydopamine-induced alterations in bloodbrain barrier permeability. Eur. J. Neurosci. 22, 1158-1168. doi: 10. 1111/j. 1460-9568. 2005. 04281. x
27. Castejón, O. J. (2011). Ultrastructural pathology of cortical capillary pericytes in human traumatic brain oedema. Folia Neuropathol. 49, 162-173.
28. Céspedes, Á. E., Arango, C. A., and Cardona, G. P. (2013). Análisis comparativo de marcadores de lesión en modelos de isquemia cerebral focal y global en ratas. Biomedica 33, 292-305. doi: 10. 7705/biomedica. v33i2. 830
29. Chen, X., Lan, X., Roche, I., Liu, R., and Geiger, J. D. (2008). Caffeine protects against MPTP induced blood-brain barrier dysfunction in mouse striatum. J. Neurochem. 107, 1147-1157. doi: 10. 1111/j. 1471-4159. 2008. 05697. x
30. Chen, Y., and Swanson, R. A. (2003). Astrocytes and brain injury. J. Cereb. Blood Flow Metab. 23, 137-149. doi: 10. 1097/00004647-200302000-00001
31. Chinta, S., and Andersen, J. (2008). Redox imbalance in Parkinson. Biochim. Biophys. Acta 1780, 1362-1367. doi: 10. 1016/j. bbagen. 2008. 02. 005
32. Colangelo, A. M., Alberghina, L., and Papa, M. (2014). Astrogliosis as a therapeutic target for neurodegenerative diseases. Neurosci. Lett. 565, 59-64. doi: 10. 1016/j. neulet. 2014. 01. 014
33. Croisier, E., and Graeber, M. B. (2006). Glial degeneration and reactive gliosis in alpha-synucleinopathies: the emerging concept of primary gliodegeneration. Acta Neuropathol. 112, 517-530. doi: 10. 1007/s00401-006-0119-z
34. Damier, P., Hirsch, E. C., Zhang, P., Agid, Y., and Javoy-Agid, F. (1993). Glutathione peroxidase, glial cells and Parkinson's disease. Neuroscience 52, 1-6. doi: 10. 1016/0306-4522(93)90175-f
35. Daneman, R. (2012). The blood-brain barrier in health and disease. Ann. Neurol. 72, 648-672. doi: 10. 1002/ana. 23648
36. de Oliveira, D. M., Barreto, G., Galeano, P., Romero, J. I., Holubiec, M. I., Badorrey, M. S., et al. (2011). Paullinia cupana Mart. var. Sorbilis protects human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity. Hum. Exp. Toxicol. 30, 1382-1391. doi: 10. 1177/0960327110389837
37. Dejana, E. (2004). Endothelial cell-cell junctions: happy together. Nat. Rev. Mol. Cell Biol. 5, 261-270. doi: 10. 1038/nrm1357
38. del Zoppo, G. J., and Milner, R. (2006). Integrin-matrix interactions in the cerebral microvasculature. Arterioscler. Thromb. Vasc. Biol. 26, 1966-1975. doi: 10. 1161/01. atv. 0000232525. 65682. a2
39. Desai Bradaric, B., Patel, A., Schneider, J. A., Carvey, P. M., and Hendey, B. (2012). Evidence for angiogenesis in Parkinson's disease, incidental Lewy body disease, and progressive supranuclear palsy. J. Neural Transm. 119, 59-71. doi: 10. 1007/s00702-011-0684-8
40. Dickson, D. W. (2012). Parkinson's disease and parkinsonism: neuropathology. Cold Spring Harb. Perspect. Med. 2:a009258. doi: 10. 1101/cshperspect. a009258
41. Dickson, D. W., Bergeron, C., Chin, S. S., Duyckaerts, C., Horoupian, D., Ikeda, K., et al. (2002). Office of rare diseases neuropathologiccriteria for corticobasal degeneration. J. Neuropathol. Exp. Neurol. 61, 935-946.
42. Dore-Duffy, P. (2008). Pericytes: pluripotent cells of the blood brain barrier. Curr. Pharm. Des. 14, 1581-1593. doi: 10. 2174/138161208784705469
43. Dore-Duffy, P., and Cleary, K. (2011). Morphology and properties of pericytes. Methods Mol. Biol. 686, 49-68. doi: 10. 1007/978-1-60761-938-3_2
44. Dringen, R. (2000). Metabolism and functions of glutathione in brain. Prog. Neurobiol. 62, 649-671. doi: 10. 1016/s0301-0082(99)00060-x
45. Duffy, P., Schmandke, A., Schmandke, A. C., Sigworth, J., Shuh, N., Cafferty, W. B., et al. (2009). Rho-associated kinase II (ROCKII) limits axonal growth after trauma within the adult mouse spinal cord. J. Neurosci. 29, 15266-15276. doi: 10. 1523/JNEUROSCI. 4650-09. 2009
46. Elali, A., Thériault, P., and Rivest, S. (2014). The role of pericytes in neurovascular unit remodeling in brain disorders. Int. J. Mol. Sci. 15, 6453-6474. doi: 10. 3390/ijms15046453
47. Enciu, A. M., and Popescu, B. O. (2013). Is there a causal link between inflammation and dementia? Biomed Res. Int. 2013:316495. doi: 10. 1155/2013/316495
48. Fernandez, H. H. (2012). Updates in the medical management of Parkinson disease. Cleve. Clin. J. Med. 79, 28-35. doi: 10. 3949/ccjm. 78gr. 11005
49. Fitch, M. T., and Silver, J. (2008). CNS injury, glial scars and inflammation: inhibitory extracellular matrices and regeneration failure. Exp. Neurol. 209, 294-301. doi: 10. 1016/j. expneurol. 2007. 05. 014
50. Fukui, K., Onodera, K., Shinkai, T., Suzuki, S., and 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
51. Gill, S. S., Patel, N. K., Hotton, G. R., O'Sullivan, K., McCarter, R., Bunnage, M., et al. (2003). Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat. Med. 9, 589-595. doi: 10. 1038/nm850
52. Giordano, G., Kavanagh, T. J., and Costa, L. G. (2009). Mouse cerebellar astrocytes protect cerebellar granule neurons against toxicity of the polybrominateddiphenyl ether (PBDE) mixture DE-71. Neurotoxicology 30, 326-329. doi: 10. 1016/j. neuro. 2008. 12. 009
53. Grammas, P., Martinez, J., and Miller, B. (2011). Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases. Expert Rev. Mol. Med. 13:e19. doi: 10. 1017/s1462399411001918
54. Gu, X. L., Long, C. X., Sun, L., Xie, C., Lin, X., and Cai, H. (2010). Astrocytic expression of Parkinson's disease-related A53T α-synuclein causes neurodegeneration in mice. Mol. Brain 3:12. doi: 10. 1186/1756-6606-3-12
55. Halliday, G. M., and Stevens, C. H. (2011). Glia: initiators and progressors of pathology in Parkinson's disease. Mov. Disord. 26, 6-17. doi: 10. 1002/mds. 23455
56. Hamby, M. E., and Sofroniew, M. V. (2010). Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics 7, 494-506. doi: 10. 1016/j. nurt. 2010. 07. 003
57. Haseloff, R. F., Blasig, I. E., Bauer, H. C., and Bauer, H. (2005). In search of the astrocytic factor(s) modulating blood-brain barrier functions in brain capillary endothelial cells in vitro. Cell. Mol. Neurobiol. 25, 25-39. doi: 10. 1007/s10571-004-1375-x
58. Hauser, R. A. (2011). Future treatments for Parkinsons disease: surfing the PD pipeline. Int. J. Neurosci. 121(Suppl. 2), 53-62. doi: 10. 3109/00207454. 2011. 620195
59. Haussermann, P., Kuhn, W., Przuntek, H., and Muller, T. (2001). Integrity of the blood-cerebrospinal fluid barrier in early Parkinson's disease. Neurosci. Lett. 300, 182-184. doi: 10. 1016/s0304-3940(01)01574-9
60. Hawkins, B. T., and Davis, T. P. (2005). The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev. 57, 173-185. doi: 10. 1124/pr. 57. 2. 4
61. Hirano, S., Asanuma, K., Ma, Y., Tang, C., Feigin, A., Dhawan, V., et al. (2008). Dissociation of metabolic and neurovascular responses to levodopa in the treatment of Parkinson's disease. J. Neurosci. 28, 4201-4209. doi: 10. 1523/JNEUROSCI. 0582-08. 2008
62. Hirsch, E. C., Breidert, T., Rousselet, E., Hunot, S., Hartmann, A., and Michel, P. P. (2003). The role of glial reaction and inflammation in Parkinson's disease. Ann. N Y Acad. Sci. 991, 214-228. doi: 10. 1111/j. 1749-6632. 2003. tb07478. x
63. Huang, B., Krafft, P. R., Ma, Q., Rolland, W. B., Caner, B., Lekic, T., et al. (2012). Fibroblast growth factors preserve blood-brain barrier integrity through RhoA inhibition after intracerebral hemorrhage in mice. Neurobiol. Dis. 46, 204-214. doi: 10. 1016/j. nbd. 2012. 01. 008
64. Hurtado-Alvarado, G., Cabañas-Morales, A. M., and Gómez-González, B. (2014). Pericytes: brain immune interface modulators. Front. Integr. Neurosci. 7:80. doi: 10. 3389/fnint. 2013. 00080
65. Itoh, N., and Ornitz, D. M. (2011). Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease. J. Biochem. 149, 121-130. doi: 10. 1093/jb/mvQ181
66. Jangula, A., and Murphy, E. J. (2013). Lipopolysaccharide-induced blood brain barrier permeability is enhanced by alpha-synuclein expression. Neurosci. Lett. 551, 23-27. doi: 10. 1016/j. neulet. 2013. 06. 058
67. Jankovic, J., and Poewe, W. (2012). Therapies in Parkinson's disease. Curr. Opin. Neurol. 25, 433-447. doi: 10. 1097/WCO. 0b013e3283542fc2
68. Jenner, P. (2003). Oxidative stress in Parkinson's disease. Ann. Neurol. 53(Suppl. 3), S26-S36; discussion S36-S38. doi: 10. 1002/ana. 10483
69. Kang, W., and Hebert, J. M. (2011). Signaling pathways in reactive astrocytes, a genetic perspective. Mol. Neurobiol. 43, 147-154. doi: 10. 1007/s12035-011-8163-7
70. Kim, G. W., Lewén, A., Copin, J., Watson, B. D., and Chan, P. H. (2001). The cytosolic antioxidant, copper/zinc superoxide dismutase, attenuates blood-brain barrier disruption and oxidative cellular injury after photothrombotic cortical ischemia in mice. Neuroscience 105, 1007-1018. doi: 10. 1016/s0306-4522(01)00237-8
71. Kim, G. W., Gasche, Y., Grzeschik, S., Copin, J. C., Maier, C. M., and Chan, P. H. (2003). Neurodegeneration in striatum induced by the mitochondrial toxin 3-nitropropionic acid: role of matrix metalloproteinase-9 in early blood-brain barrier disruption? J. Neurosci. 23, 8733-8742.
72. Kimelberg, H. K., and Nedergaard, M. (2010). Functions of astrocytes and their potential as therapeutic targets. Neurotherapeutics 7, 338-353. doi: 10. 1016/j. nurt. 2010. 07. 006
73. Kondo, T., Reaume, A. G., Huang, T. T., Carlson, E., Murakami, K., Chen, S. F., et al. (1997). Reduction of CuZn superoxide dismutase activity exacerbates neuronal cell injury and edema formation aftertransient focal cerebral ischemia. J. Neurosci. 17, 4180-41899.
74. Kortekaas, R., Leenders, K. L., van Oostrom, J. C., Vaalburg, W., Bart, J., Willemsen, A. T., et al. (2005). Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann. Neurol. 57, 176-179. doi: 10. 1002/ana. 20369
75. Kurkowska-Jastrzebska, I., Wrónska, A., Kohutnicka, M., Czlonkowski, A., and Czlonkowski, A. (1999). The inflammatory reaction following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication in mouse. Exp. Neurol. 156, 50-61. doi: 10. 1006/exnr. 1998. 6993
76. Lange, S., Trost, A., Tempfer, H., Bauer, H. C., Bauer, H., Rohde, E., et al. (2013). Brain pericyte plasticity as a potential drug target in CNS repair. Drug Discov. Today 18, 456-463. doi: 10. 1016/j. drudis. 2012. 12. 007
77. Langston, J. W., Forno, L. S., Tetrud, J., Reeves, A. G., Kaplan, J. A., and Karluk, D. (1999). Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann. Neurol. 46, 598-605. doi: 10. 1002/1531-8249(199910)46:4<598::aid-ana7>3. 0. co;2-f
78. Lau, L. W., Cua, R., Keough, M. B., Haylock-Jacobs, S., and Yong, V. W. (2013). Pathophysiology of the brain extracellular matrix: a new target for remyelination. Nat. Rev. Neurosci. 14, 722-729. doi: 10. 1038/nrn3550
79. Lee, H., and Pienaar, I. S. (2014). Disruption of the blood-brain barrier in Parkinson's disease: curse or route to a cure? Front. Biosci. (Landmark Ed.) 19, 272-280. doi: 10. 2741/4206
80. Lee, S. J., Kim, J. S., Lee, K. S., An, J. Y., Kim, W., Kim, Y. I., et al. (2009). The severity of leukoaraiosis correlates with the clinical phenotype of Parkinson's disease. Arch. Gerontol. Geriatr. 49, 255-259. doi: 10. 1016/j. archger. 2008. 09. 005
81. Lin, J. L., Huang, Y. H., Shen, Y. C., Huang, H. C., and Liu, P. H. (2010). Ascorbic acidprevents bloodbrain barrier disruption and sernsory deficit caused by sustained compressio ofprimary somatosensory cortex. J. Cereb. Blood Flow Metab. 30, 1121-1136. doi: 10. 1038/jcbfm. 2009. 277
82. Lindenau, J., Noack, H., Possel, H., Asayama, K., and Wolf, G. (2000). Cellular distribution of superoxide dismutases in the rat CNS. Glia 29, 25-34. doi: 10. 1002/(sici)1098-1136(20000101)29:1<25::aid-glia3>3. 0. co;2-g
83. Luissint, A. C., Artus, C., Glacial, F., Ganeshamoorthy, K., and Couraud, P. O. (2012). Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation. Fluids Barriers CNS 9:23. doi: 10. 1186/2045-8118-9-23
84. Maier, C. M., and Chan, P. H. (2002). Role of superoxide dismutases in oxidative damage and neurodegenerative disorders. Neuroscientist 8, 323-334. doi: 10. 1177/107385840200800408
85. Maragakis, N. J., and Rothstein, J. D. (2006). Mechanisms of disease: astrocytes in neurode generative disease. Nat. Clin. Pract. Neurol. 2, 679-689. doi: 10. 1038/ncpneuro0355
86. Mattson, M. P. (2008). Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann. N Y Acad. Sci. 1144, 97-112. doi: 10. 1196/annals. 1418. 005
87. Minagar, A., and Alexander, J. S. (2003). Blood brain barrier disruption in multiple sclerosis. Mult. Scler. 9, 540-549. doi: 10. 1191/1352458503ms965oa
88. Mokgokong, R., Wang, S., Taylor, C. J., Barrand, M. A., and Hladky, S. B. (2014). Ion transporters in brain endothelial cells that contribute to formation of brain interstitial fluid. Pflugers Arch. 466, 887-901. doi: 10. 1007/s00424-013-1342-9
89. Mythri, R. B., Venkateshappa, C., Harish, G., Mahadevan, A., Muthane, U. B., Yasha, T. C., et al. (2011). Evaluation of markers of oxidative stress, antioxidant function and astrocytic proliferation in the striatum and frontal cortex of Parkinson's disease brains. Neurochem. Res. 36, 1452-1463. doi: 10. 1007/s11064-011-0471-9
90. Nag, S. (2011). Morphology and properties of brain endothelial cells. Methods Mol. Biol. 686, 3-47. doi: 10. 1007/978-1-60761-938-3_1
91. Najjar, S., Pearlman, D. M., Devinsky, O., Najjar, A., and Zagzag, D. (2013). Neurovascular unit dysfunction with blood brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence. J. Neuroinflammation 10:142. doi: 10. 1186/1742-2094-10-142
92. Niranjan, R., Nath, C., and Shukla, R. (2010). The mechanism of action of MPTP-induced neuroinflammation and its modulation by melatonin in rat astrocytoma cells, C6. Free Radic. Res. 44, 1304-1316. doi: 10. 3109/10715762. 2010. 501080
93. Nutt, J. G., and Wooten, G. F. (2005). Clinical practice. Diagnosis and initial management of Parkinson's disease. N. Engl. J. Med. 353, 1021-1027. doi: 10. 1056/NEJMcp043908
94. Oberheim, N. A., Goldman, S. A., and Nedergaard, M. (2012). Heterogeneity of astrocytic form and function. Methods Mol. Biol. 814, 23-45. doi: 10. 1007/978-1-61779-452-0_3
95. Ogawa, N., Asanuma, M., Miyazaki, I., Diaz-Corrales, F. J., and Miyoshi, K. (2005). L-DOPA treatment from the viewpoint of neuroprotection. Possible mechanism of specific and progressive dopaminergic neuronal death in Parkinson's disease. J. Neurol. 252(Suppl. 4), IV23-IV31. doi: 10. 1007/s00415-005-4006-7
96. Ohlin, K. E., Francardo, V., Lindgren, H. S., Sillivan, S. E., O'Sullivan, S. S., Luksik, A. S., et al. (2011). Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia. Brain 134, 2339-2357. doi: 10. 1093/brain/awr165
97. Ossig, C., and Reichmann, H. (2013). Treatment of Parkinson's disease in the advanced stage. J. Neural Transm. 120, 523-529. doi: 10. 1007/s00702-013-1008-y
98. Pang, Y., Zheng, B., Campbell, L. R., Fan, L. W., Cai, Z., and Rhodes, P. G. (2010). IGF-1 can either protect against or increase LPS-induced damage in the developing rat brain. Pediatr. Res. 67, 579-584. doi: 10. 1203/PDR. 0b013e3181dc240f
99. Pan-Montojo, F., Anichtchik, O., Dening, Y., Knels, L., Pursche, S., Jung, R., et al. (2010). Progression of Parkinson's disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One 5:e8762. doi: 10. 1371/journal. pone. 0008762
100. Papadeas, S. T., Kraig, S. E., O'Banion, C., Lepore, A. C., and Maragakis, N. J. (2011). Astrocytes carrying the superoxide dismutase 1 (SOD1G93A) mutation induce wild-type motor neurodegeneration in vivo. Proc. Natl. Acad. Sci. U S A 108, 17803-17808. doi: 10. 1073/pnas. 1103141108
101. Parpura, V., Grubisic, V., and Verkhratsky, A. (2011). Ca(2+) sources for the exocytotic release of glutamate from astrocytes. Biochim. Biophys. Acta 1813, 984-991. doi: 10. 1016/j. bbamcr. 2010. 11. 006
102. Peterson, A. L., and Nutt, J. G. (2008). Treatment of Parkinson's disease with trophic factors. Neurotherapeutics 5, 270-280. doi: 10. 1016/j. nurt. 2008. 02. 003
103. Pilakka-Kanthikeel, S., Atluri, V. S., Sagar, V., Saxena, S. K., and Nair, M. (2013). Targeted brain derived neurotropic factors (BDNF) delivery across the blood-brain barrier for neuro-protection using magnetic nano carriers: an in-vitro study. PLoS One 8:e62241. doi: 10. 1371/journal. pone. 0062241
104. Popescu, B. O., Toescu, E. C., Popescu, L. M., Bajenaru, O., Muresanu, D. F., Schultzberg, M., et al. (2009). Blood-brain barrier alterations in ageing and dementia. J. Neurol. Sci. 283, 99-106. doi: 10. 1016/j. jns. 2009. 02. 321
105. Price, T. O., Eranki, V., Banks, W. A., Ercal, N., and Shah, G. N. (2012). Topiramate treatment protects blood-brain barrier pericytes from hyperglycemia induced oxidative damage in diabetic mice. Endocrinology 153, 362-372. doi: 10. 1210/en. 2011-1638
106. Proschel, C., Stripay, J. L., Shih, C. H., Munger, J. C., and Noble, M. D. (2014). Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons. EMBO Mol. Med. 6, 504-518. doi: 10. 1002/emmm. 201302878
107. Radunović, A., Porto, W. G., Zeman, S., and Leigh, P. N. (1997). Increased mitochondrial superoxide dismutase activity in Parkinson's disease but not amyotrophic lateral sclerosis motor cortex. Neurosci. Lett. 239, 105-108. doi: 10. 1016/s0304-3940(97)00905-1
108. Ramaswamy, S., and Kordower, J. H. (2009). Are growth factors the answer? Parkinsonism Relat. Disord. 15(Suppl. 3), S176-S180. doi: 10. 1016/S1353-8020(09)70809-0
109. Rappold, P. M., and Tieu, K. (2010). Astrocytes and therapeutics for Parkinson's disease. Neurotherapeutics 7, 413-423. doi: 10. 1016/j. nurt. 2010. 07. 001
110. Ribatti, D., Nico, B., and Crivellato, E. (2011). The role of pericytes in angiogenesis. Int. J. Dev. Biol. 55, 261-268. doi: 10. 1387/ijdb. 103167dr
111. Robel, S., Mori, T., Zoubaa, S., Schlegel, J., Sirko, S., Faissner, A., et al. (2009). Conditional deletion of beta1-integrin in astroglia causes partial reactive gliosis. Glia 57, 1630-1647. doi: 10. 1002/glia. 20876
112. Safi, R., Gardaneh, M., Panahi, Y., Maghsoudi, N., Zaefizadeh, M., and Gharib, E. (2012). Optimized quantities of GDNF overexpressed by engineered astrocytes are critical for protection of neuroblastoma cells against 6-OHDA toxicity. J. Mol. Neurosci. 46, 654-665. doi: 10. 1007/s12031-011-9654-8
113. Samantaray, S., Knaryan, V. H., Guyton, M. K., Matzelle, D. D., Ray, S. K., and Banik, N. L. (2007). The parkinsonian neurotoxin rotenone activates calpain and caspase-3 leading to motoneuron degeneration in spinal cord of Lewis rats. Neuroscience 146, 741-755. doi: 10. 1016/j. neuroscience. 2007. 01. 056
114. Sano, Y., Shimizu, F., Nakayama, H., Abe, M., Maeda, T., Ohtsuki, S., et al. (2007). Endothelial cells constituting blood nerve barrier have highly specialized characteristics as barrier-forming cells. Cell Struct. Funct. 32, 139-147. doi: 10. 1247/csf. 07015
115. Sá-Pereira, I., Brites, D., and Brito, M. A. (2012). Neurovascular unit: a focus on pericytes. Mol. Neurobiol. 45, 327-347. doi: 10. 1007/s12035-012-8244-2
116. Schinkel, A. H., Smit, J. J., van Tellingen, O., Beijnen, J. H., Wagenaar, E., van Deemter, L., et al. (1994). Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77, 491-502. doi: 10. 1016/0092-8674(94)90212-7
117. Schwartz, M. D., and Sabetay, M. D. (2012). An approach to the continuous dopaminergic stimulation in Parkinson's disease. Isr. Med. Assoc. J. 14, 175-179.
118. Shukla, A., Shukla, R., Dikshit, M., and Srimal, R. C. (1993). Alterations in free radical scavenging mechanisms following blood-brain barrier disruption. Free Radic. Biol. Med. 15, 97-100. doi: 10. 1016/0891-5849(93)90128-h
119. Simpson, I. A., Carruthers, A., and Vannucci, S. J. (2007). Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J. Cereb. Blood Flow Metab. 27, 1766-1791. doi: 10. 1038/sj. jcbfm. 9600521
120. Sims, N. R., Nilsson, M., and Muyderman, H. (2004). Mitochondrial glutathione: a modulator of brain cell death. J. Bioenerg. Biomembr. 36, 329-333. doi: 10. 1023/b:jobb. 0000041763. 63958. e7
121. Singer, C. (2012). Managing the patient with newly diagnosed Parkinson disease. Cleve. Clin. J. Med. 79(Suppl. 2), S3-S7. doi: 10. 3949/ccjm. 79. s2a. 01
122. Slemmer, J. E., Shacka, J. J., Sweeney, M. I., and Weber, J. T. (2008). Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr. Med. Chem. 15, 404-414. doi: 10. 2174/092986708783497337
123. Smeyne, M., and Smeyne, R. J. (2013). Glutathione metabolism and Parkinson's disease. Free Radic. Biol. Med. 62, 13-25. doi: 10. 1016/j. freeradbiomed. 2013. 05. 001
124. Stamatovic, S. M., Keep, R. F., and Andjelkovic, A. V. (2008). Brain endothelial cell-cell junctions: how to "open" the blood brain barrier. Curr. Neuropharmacol. 6, 179-192. doi: 10. 2174/157015908785777210
125. Stanimirovic, D. B., and Friedman, A. (2012). Pathophysiology of the neurovascular unit disease cause or consequence? J. Cereb. Blood Flow Metab. 32, 1207-1221. doi: 10. 1038/jcbfm. 2012. 25
126. Sugaya, K., Chou, S., Xu, S. J., and McKinney, M. (1998). Indicators of glial activation and brain oxidative stress after intraventricular infusion of endotoxin. Brain Res. Mol. Brain Res. 58, 1-9. doi: 10. 1016/s0169-328x(97)00365-3
127. Sullivan, A. M., and Toulouse, A. (2011). Neurotrophic factors for the treatment of Parkinson's disease. Cytokine Growth Factor Rev. 22, 157-165. doi: 10. 1016/j. cytogfr. 2011. 05. 001
128. Tanner, C. M., Kamel, F., Ross, G. W., Hoppin, J. A., Goldman, S. M., Korell, M., et al. (2011). Rotenone, paraquat and Parkinson's disease. Environ. Health Perspect. 119, 866-872. doi: 10. 1289/ehp. 1002839
129. Theis, M., Söhl, G., Eiberger, J., and Willecke, K. (2005). Emerging complexities in identity and function of glial connexins. Trends Neurosci. 28, 188-195. doi: 10. 1016/j. tins. 2005. 02. 006
130. Timmer, M., Muller-Ostermeyer, F., Kloth, V., Winkler, C., Grothe, C., and Nikkhah, G. (2004). Enhanced survival, reinnervation, and functional recovery of intrastriatal dopamine grafts co-transplanted with Schwann cells overexpressing high molecular weight FGF-2 isoforms. Exp. Neurol. 187, 118-136. doi: 10. 1016/j. expneurol. 2004. 01. 013
131. van Sorge, N. M., and Doran, K. S. (2012). Defense at the border: the blood-brain barrier versus bacterial foreigners. Future Microbiol. 7, 383-394. doi: 10. 2217/fmb. 12. 1
132. Vives-Bauza, C., and Przedborski, S. (2011). Mitophagy: the latest problem for Parkinson's disease. Trends Mol. Med. 17, 158-165. doi: 10. 1016/j. molmed. 2010. 11. 002
133. Volterra, A., and Meldolesi, J. (2005). Astrocytes, from brain glue to communication elements: the revolution continues. Nat. Rev. Neurosci. 6, 626-640. doi: 10. 1038/nrn1722
134. Wada, K., Arai, H., Takanashi, M., Fukae, J., Oizumi, H., Yasuda, T., et al. (2006). Expression levels of vascular endothelial growth factor and its receptors in Parkinson's disease. Neuroreport 7, 705-709. doi: 10. 1097/01. wnr. 0000215769. 71657. 65
135. Wang, H. L., Chou, A. H., Wu, A. S., Chen, S. Y., Weng, Y. H., Kao, Y. C., et al. (2011). PARK6 PINK1 mutants are defective in maintaining mitochondrial membrane potential and inhibiting ROS formation of substantia nigra dopaminergic neurons. Biochim. Biophys. Acta 1812, 674-684. doi: 10. 1016/j. bbadis. 2011. 03. 007
136. Wolburg, H., Noell, S., Mack, A., Wolburg-Buchholz, K., and Fallier-Becker, P. (2009). Brain endothelial cells and the glio-vascular complex. Cell Tissue Res. 335, 75-96. doi: 10. 1007/s00441-008-0658-9
137. Wong, A. D., Ye, M., Levy, A. F., Rothstein, J. D., Bergles, D. E., and Searson, P. C. (2013). The blood-brain barrier: an engineering perspective. Front. Neuroeng. 6:7. doi: 10. 3389/fneng. 2013. 00007
138. Wong, D., Dorovini-Zis, K., and Vincent, S. R. (2004). Cytokines, nitric oxide and cGMP modulate the permeability of an in vitro model of the human blood-brain barrier. Exp. Neurol. 190, 446-455. doi: 10. 1016/j. expneurol. 2004. 08. 008
139. Xiong, X., Barreto, G. E., Xu, L., Ouyang, Y. B., Xie, X., and Giffard, R. G. (2011). Increased brain injury and worsened neurological outcome in interleukin-4 knockout mice after transient focal cerebral ischemia. Stroke 42, 2026-2032. doi: 10. 1161/STROKEAHA. 110. 593772
140. Yasuda, T., and Mochizuki, H. (2010). Use of growth factors for the treatment of Parkinson's disease. Expert Rev. Neurother. 10, 915-924. doi: 10. 1586/ern. 10. 55
141. Zechariah, A., Elali, A., Doeppner, T. R., Jin, F., Hasan, M. R., Helfrich, I., et al. (2013). Vascular endothelial growth factor promotes pericyte coverage of brain capillaries, improves cerebral blood flow during subsequent focal cerebral ischemia and preserves the metabolic penumbra. Stroke 44, 1690-1697. doi: 10. 1161/STROKEAHA. 111. 000240
142. Zheng, L., Ishii, Y., Tokunaga, A., Hamashima, T., Shen, J., Zhao, Q. L., et al. (2010). Neuroprotective effects of PDGF against oxidative stress and the signaling pathway involved. J. Neurosci. Res. 88, 1273-1284. doi: 10. 1002/jnr. 22302
143. Zonta, M., Angulo, M. C., Gobbo, S., Rosengarten, B., Hossmann, K. A., Pozzan, T., et al. (2003). Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat. Neurosci. 6, 43-50. doi: 10. 1038/nn980