Expression of the Nrf2-system at the blood-CSF barrier is modulated by neonatal inflammation and hypoxia-ischemia

详细信息    查看全文

• 作者：Barbara D’Angelo (1)
  C. Joakim Ek (1)
  Mats Sandberg (2)
  Carina Mallard (1)
  
• 刊名：Journal of Inherited Metabolic Disease
• 出版年：2013
• 出版时间：May 2013
• 年：2013
• 卷：36
• 期：3
• 页码：479-490
• 全文大小：853KB
• 参考文献：1. Beiswanger CM, Diegmann MH, Novak RF et al (1995) Developmental changes in the cellular distribution of glutathione and glutathione S-transferases in the murine nervous system. Neurotoxicol 16:425-40
  2. Borst P, Evers R, Kool M, Wijnholds J (2000) A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst 92:1295-302 CrossRef
  3. Calkins MJ, Vargas MR, Johnson DA, Johnson JA (2010) Astrocyte-specific overexpression of Nrf2 protects striatal neurons from mitochondrial complex II inhibition. Toxicol Sci 115:557-68 CrossRef
  4. Chen PC, Vargas MR, Pani AK et al (2009) Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson’s disease: Critical role for the astrocyte. Proc Natl Acad Sci USA 106:2933-938 CrossRef
  5. Correa F, Ljunggren E, Mallard C, Nilsson M, Weber SG, Sandberg M (2011) The Nrf2-inducible antioxidant defense in astrocytes can be both up- and down-regulated by activated microglia: Involvement of p38 MAPK. Glia 59:785-99 CrossRef
  6. Ek CJ, Habgood MD, Dziegielewska KM, Saunders NR (2003) Structural characteristics and barrier properties of the choroid plexuses in developing brain of the opossum (Monodelphis Domestica). J Comp Neurol 460:451-64 CrossRef
  7. Ek CJ, Wong A, Liddelow SA, Johansson PA, Dziegielewska KM, Saunders NR (2010) Efflux mechanisms at the developing brain barriers: ABC-transporters in the fetal and postnatal rat. Toxicol Lett 197:51-9 CrossRef
  8. Ek CJ, Dziegielewska KM, Habgood MD, Saunders NR (2012) Barriers in the developing brain and Neurotoxicology. Neurotoxicol 33:586-04 CrossRef
  9. Eklind S, Mallard C, Leverin AL et al (2001) Bacterial endotoxin sensitizes the immature brain to hypoxic–ischaemic injury. Eur J Neurosci 13(6):1101-106 CrossRef
  10. Ferriero DM (2001) Oxidant mechanisms in neonatal hypoxia-ischemia. Dev Neurosci 23:198-02 CrossRef
  11. Garbuzova-Davis S, Louis MK, Haller EM, Derasari HM, Rawls AE, Sanberg PR (2011) Blood–brain barrier impairment in an animal model of MPS III B. PLoS One 6:e16601. doi:10.1371/journal.pone.0016601 CrossRef
  12. Gazzin S, Strazielle N, Schmitt C et al (2008) Differential expression of the multidrug resistance-related proteins ABCb1 and ABCc1 between blood–brain interfaces. J Comp Neurol 510:497-07 CrossRef
  13. Ghersi-Egea JF, Strazielle N, Murat A, Jouvet A, Buenerd A, Belin MF (2006) Brain protection at the blood-cerebrospinal fluid interface involves a glutathione-dependent metabolic barrier mechanism. J Cereb Blood Flow Metab 26:1165-175
  14. Gulcan H, Ozturk IC, Arslan S (2005) Alterations in antioxidant enzyme activities in cerebrospinal fluid related with severity of hypoxic ischemic encephalopathy in newborns. Biol Neonate 88:87-1 CrossRef
  15. Hedtj?rn M, Leverin AL, Eriksson K, Blomgren K, Mallard C, Hagberg H (2002) Interleukin-18 involvement in hypoxic-ischemic brain injury. J Neurosci 22:5910-919
  16. Huber JD, Campos CR, Mark KS, Davis TP (2006) Alterations in blood–brain barrier ICAM-1 expression and brain microglial activation after lambda-carrageenan-induced inflammatory pain. Am J Physiol Heart Circ Physiol 290:H732-40 CrossRef
  17. Innamorato NG, Rojo AI, Garcia-Yague AJ, Yamamoto M, de Ceballos ML, Cuadrado A (2008) The transcription factor Nrf2 is a therapeutic target against brain inflammation. J Immunol 181:680-89
  18. Itoh S, Yanagishita T, Aoki S et al (1999) Generation of free radicals and the damage done to the sarcoplasmic reticulum during reperfusion injury following brief ischemia in the canine heart. Jpn Circ J 63:373-78 CrossRef
  19. Johanson CE (1995) Ventricles and cerebrospinal fluid. In: Conn PM (ed) Neuroscience in medicine. J.B Lippincott Company, Philadelphia, pp 171-96
  20. Johanson CE, Jones HC, Stopa EG, Ayala C, Duncan JA, McMillan PN (2002) Enhanced expression of the NA-K-2 Cl cotransporter at different regions of the blood-CSF barrier in the perinatal H-Tx rat. Eur J Pediatr Surg 12:S47-9
  21. Johansson PA, Dziegielewska KM, Ek CJ et al (2006) Blood-CSF barrier function in the rat embryo. Eur J Neurosci 24:65-6 CrossRef
  22. Johnson DA, Andrews GK, Xu W, Johnson JA (2002) Activation of the antioxidant response element in primary cortical neuronal cultures derived from transgenic reporter mice. J Neurochem 81:1233-241 CrossRef
  23. Kauffmann HM, Pfannschmidt S, Zoller H et al (2002) Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2 gene expression. Toxicology 171:137-46 CrossRef
  24. Klaassen CD, Slitt A (2005) Regulation of hepatic transporters by xenobiotic receptors. Curr Drug Metab 6:309-28 CrossRef
  25. Ko K, Yang H, Noureddin M et al (2008) Changes in S-adenosylmethionine and GSH homeostasis during endotoxemia in mice. Lab Invest 88:1121-129 CrossRef
  26. Kwak MK, Wakabayashi N, Itoh K, Motohashi H, Yamamoto M, Kensler TW (2003) Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1–Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem 278:8135-145 CrossRef
  27. Laflamme N, Rivest S (2001) Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall components. FASEB J 15:155-3 CrossRef
  28. Lee JM, Shih AY, Murphy TH, Johnson JA (2003) NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J Biol Chem 278:37948-7956 CrossRef
  29. Liddelow SA, Temple S, M?llg?rd K et al (2012) Molecular characterisation of transport mechanisms at the developing mouse blood-CSF interface: a transcriptome approach. PLoS One 7:e33554. doi:10.1371/journal.pone.0033554 CrossRef
  30. Maeda S, Nakatsuka I, Hayashi Y, Higuchi H, Shimada M, Miyawaki T (2008) Heme oxygenase-1 induction in the brain during lipopolysaccharide-induced acute inflammation. Neuropsychiatr Dis Treat 4:663-67 CrossRef
  31. Marques F, Sousa JC, Coppola G et al (2009) Kinetic profile of the transcriptome changes induced in the choroid plexus by peripheral inflammation. J Cereb Blood Flow Metab 29:921-32 CrossRef
  32. Meijerman I, Beijnen JH, Schellens JH (2008) Combined action and regulation of phase II enzymes and multidrug resistance proteins in multidrug resistance in cancer. Cancer Treat Rev 34:505-20 CrossRef
  33. Nagai N, Thimmulappa RK, Cano M et al (2009) Nrf2 is a critical modulator of the innate immune response in a model of uveitis. Free Radic Biol Med 47:300-06 CrossRef
  34. Ogihara T, Hirano K, Ogihara H et al (2003) Non-protein-bound transition metals and hydroxyl radical generation in cerebrospinal fluid of newborn infants with hypoxic ischemic encephalopathy. Pediatr Res 53:594-99 CrossRef
  35. Ping Z, Liu W, Kang Z et al (2010) Sulforaphane protects brains against hypoxic-ischemic injury through induction of Nrf2-dependent phase 2 enzyme. Brain Res 1343:178-85 CrossRef
  36. Rothstein RP, Levison SW (2002) Damage to the choroid plexus, ependyma and subependyma as a consequence of perinatal hypoxia/ischemia. Dev Neurosci 24:426-36 CrossRef
  37. Saha A, Sarkar C, Singh SP et al (2012) The blood–brain barrier is disrupted in a mouse model of infantile neuronal ceroid lipofuscinosis: amelioration by resveratrol. Hum Mol Genet 21:2233-244 CrossRef
  38. S?vman K, Nilsson UA, Blennow M, Kjellmer I, Whitelaw A (2001) Non-protein-bound iron is elevated in cerebrospinal fluid from preterm infants with posthemorrhagic ventricular dilatation. Pediatr Res 49:208-12 CrossRef
  39. Schipper HM, Song W, Zukor H, Hascalovici JR, Zeligman D (2009) Heme oxygenase-1 and neurodegeneration: expanding frontiers of engagement. J Neurochem 110:469-85 CrossRef
  40. Senjo M, Ishibashi T, Terashima T, Inoue Y (1986) Successive appearance of glutathione S-transferase-positive cells in developing rat brain: choroid plexus, pia mater, ventricular zone and astrocytes. Neurosci Lett 66:131-34 CrossRef
  41. Shih AY, Imbeault S, Barakauskas V, Erb H, Jiang L, Li P, Murphy TH (2005) Induction of the Nrf2-driven antioxidant response confers neuroprotection during mitochondrial stress in vivo. J Biol Chem 280:22925-2936 CrossRef
  42. Strazielle N, Ghersi-Egea JF (2000) Choroid plexus in the central nervous system: biology and physiopathology. J Neuropathol Exp Neurol 59:561-74
  43. Strazielle N, Khuth ST, Ghersi-Egea JF (2004) Detoxification systems, passive and specific transport for drugs at the blood-CSF barrier in normal and pathological situations. Adv Drug Deliv Rev 56:1717-740 CrossRef
  44. Sun Y, Liou B, Ran H et al (2010) Neuronopathic Gaucher disease in the mouse: viable combined selective saposin C deficiency and mutant glucocerebrosidase (V394L) mice with glucosylsphingosine and glucosylceramide accumulation and progressive neurological deficits. Hum Mol Genet 19:1088-097 CrossRef
  45. Svedin P, Hagberg H, S?vman K, Zhu C, Mallard C (2007) Matrix metalloproteinase-9 gene knock-out protects the immature brain after cerebral hypoxia-ischemia. J Neurosci 27:1511-518 CrossRef
  46. Tirona RG, Kim RB (2005) Nuclear receptors and drug disposition gene regulation. J Pharm Sci 94:1169-186 CrossRef
  47. Vargas MR, Johnson DA, Sirkis DW, Messing A, Johnson JA (2008) Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis. J Neurosci 28:13574-3581 CrossRef
  48. Wang X, Svedin P, Nie C et al (2007) N-acetylcysteine reduces lipopolysaccharide-sensitized hypoxic-ischemic brain injury. Ann Neurol 61:263-71 CrossRef
  49. Wang X, Stridh L, Li W et al (2009) Lipopolysaccharide sensitizes neonatal hypoxic-ischemic brain injury in a MyD88-dependent manner. J Immunol 183:7471-477 CrossRef
  50. Wasserman WW, Fahl WE (1997) Functional antioxidant responsive elements. Proc Natl Acad Sci USA 94:5361-266 CrossRef
  51. Wiesel P, Foster LC, Pellacani A et al (2000) Thioredoxin facilitates the induction of heme oxygenase-1 in response to inflammatory mediators. J Biol Chem 275:24840-4846 CrossRef
  52. Wu YP, Proia RL (2004) Deletion of macrophage-inflammatory protein 1 alpha retards neurodegeneration in Sandhoff disease mice. Proc Natl Acad Sci USA 101:8425-430 CrossRef
  53. Xiang J, Alesi GN, Zhou N, Keep RF (2012) Protective effects of isothiocyanates on blood-CSF barrier disruption induced by oxidative stress. Am J Physiol Regul Integr Comp Physiol 303:R1-. doi:10.1152/ajpregu.00518.2011 CrossRef
  54. Zhao J, Moore AN, Redell JB, Dash PK (2007) Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury. J Neurosci 27:10240-0248 CrossRef
  
• 作者单位：Barbara D’Angelo (1)
  C. Joakim Ek (1)
  Mats Sandberg (2)
  Carina Mallard (1)
  
  1. Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  2. Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  
• ISSN：1573-2665

文摘

Transcription factor NF-E2-related factor-2 (Nrf2) is a key regulator of endogenous anti-oxidant systems shown to play a neuroprotective role in the adult by preserving blood–brain barrier function. The choroid plexus, site for the blood-CSF barrier, has been suggested to be particularly important in maintaining brain barrier function in development. We investigated the expression of Nrf2- and detoxification-system genes in choroid plexus following systemic LPS injections, unilateral cerebral hypoxia-ischemia (HI) as well as the combination of LPS and HI (LPS/HI). Plexuses were collected at different time points after LPS, HI and LPS/HI in 9-day old mice. mRNA levels of Nrf2 and many of its target genes were analyzed by quantitative PCR. Cell death was analyzed by caspase-3 immunostaining and TUNEL. LPS caused down-regulation of the Nrf2-system genes while HI increased expression at earlier time points. LPS exposure prior to HI prevented many of the HI-induced gene increases. None of the insults resulted in any apparent cell death to choroidal epithelium. These data imply that the function of the inducible anti-oxidant system in the choroid plexus is down-regulated by inflammation, even if choroid cells are not structurally damaged. Further, LPS prevented the endogenous antioxidant response following HI, suggesting the possibility that the choroid plexus may be at risk if LPS is united with an insult that increases oxidative stress such as hypoxia-ischemia.