DOI QR코드

DOI QR Code

Different expressions of AQP1, AQP4, eNOS, and VEGF proteins in ischemic versus non-ischemic cerebropathy in rats: potential roles of AQP1and eNOS in hydrocephalic and vasogenic edema formation

  • Kim, Jae-Hyun (Department of Anatomy, Dongguk University College of Medicine) ;
  • Jung, Yong-Wook (Department of Anatomy, Dongguk University College of Medicine)
  • Published : 2011.12.31

Abstract

In this study, expressions of aquaporin (AQP) 1, AQP4, endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor in blood-cerebrospinal fluid (CSF) barrier and blood-brain barrier (BBB) are examined in rat choroid plexus and peri-infarcted hippocampal formation (HF) following systemic hyponatremia (SH) and permanent middle cerebral artery occlusion (pMCAO). These events are thought to cause the development of hydrocephalic and vasogenic edemas. The importance of CSF overproduction and intact blood-CSF barrier during hydrocephalic edema formation is demonstrated by the high expression of AQP1 (329.86${\pm}$10.2%, n=4 , P<0.01) and trapped plasma immunoglobulin G (IgG) in choroid plexus epithelium after 24 hours of SH. However, the increased eNOS expression in peri-infarcted HF (130${\pm}$3%, n=4, P<0.01) and extravasation of plasma IgG into the extravascular compartment after 24 hours of pMCAO suggest that increased microvascular permeability, probably due to elevated levels of nitric oxide, leads to development of vasogenic brain edema via BBB breakdown. Based on these findings, the authors suggest that modulation of different protein expression, dependent on the type of brain edema, is required for primary (pMCAO) and secondary (SH) brain injuries to attenuate brain edema and neuronal degeneration.

Keywords

References

  1. Kimelberg HK. Current concepts of brain edema. Review of laboratory investigations. J Neurosurg 1995;83:1051-9. https://doi.org/10.3171/jns.1995.83.6.1051
  2. Blei AT. Pathophysiology of brain edema in fulminant hepatic failure, revisited. Metab Brain Dis 2001;16:85-94. https://doi.org/10.1023/A:1011670713730
  3. Jung YW, Choi IJ, Kwon TH. Altered expression of sodium transporters in ischemic penumbra after focal cerebral ischemia in rats. Neurosci Res 2007;59:152-9. https://doi.org/10.1016/j.neures.2007.06.1470
  4. Klatzo I. Evolution of brain edema concepts. Acta Neurochir Suppl (Wien) 1994;60:3-6.
  5. Papadopoulos MC, Manley GT, Krishna S, Verkman AS. Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J 2004;18:1291-3. https://doi.org/10.1096/fj.04-1723fje
  6. Spector R, Johanson CE. The mammalian choroid plexus. Sci Am 1989;261:68-74.
  7. Nielsen S, Smith BL, Christensen EI, Agre P. Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. Proc Natl Acad Sci U S A 1993;90:7275-9. https://doi.org/10.1073/pnas.90.15.7275
  8. Oshio K, Song Y, Verkman AS, Manley GT. Aquaporin-1 deletion reduces osmotic water permeability and cerebrospinal fluid production. Acta Neurochir Suppl 2003;86:525-8.
  9. Oshio K, Watanabe H, Song Y, Verkman AS, Manley GT. Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin-1. FASEB J 2005;19:76-8. https://doi.org/10.1096/fj.04-1711fje
  10. Crone C. Modulation of solute permeability in microvascular endothelium. Fed Proc 1986;45:77-83.
  11. Nielsen S, Nagelhus EA, Amiry-Moghaddam M, Bourque C, Agre P, Ottersen OP. Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci 1997;17:171-80.
  12. Papadopoulos MC, Verkman AS. Aquaporin-4 and brain edema. Pediatr Nephrol 2007;22:778-84. https://doi.org/10.1007/s00467-006-0411-0
  13. Inoue H, Ando K, Wakisaka N, Matsuzaki K, Aihara M, Kumagai N. Effects of nitric oxide synthase inhibitors on vascular hyperpermeability with thermal injury in mice. Nitric Oxide 2001;5:334-42. https://doi.org/10.1006/niox.2001.0350
  14. Takeda M, Mori F, Yoshida A, Takamiya A, Nakagomi S, Sato E, Kiyama H. Constitutive nitric oxide synthase is associated with retinal vascular permeability in early diabetic rats. Diabetologia 2001;44:1043-50. https://doi.org/10.1007/s001250100588
  15. Lum H, Malik AB. Regulation of vascular endothelial barrier function. Am J Physiol 1994;267(3 Pt 1):L223-41.
  16. Garcia JG, Schaphorst KL. Regulation of endothelial cell gap formation and paracellular permeability. J Investig Med 1995;43:117-26.
  17. Feng D, Nagy JA, Hipp J, Dvorak HF, Dvorak AM. Vesiculovacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin. J Exp Med 1996;183:1981-6. https://doi.org/10.1084/jem.183.5.1981
  18. Harrigan MR, Ennis SR, Masada T, Keep RF. Intraventricular infusion of vascular endothelial growth factor promotes cerebral angiogenesis with minimal brain edema. Neurosurgery 2002;50:589-98.
  19. Hasegawa H, Ma T, Skach W, Matthay MA, Verkman AS. Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues. J Biol Chem 1994;269:5497-500.
  20. Praetorius J. Water and solute secretion by the choroid plexus. Pflugers Arch 2007;454:1-18. https://doi.org/10.1007/s00424-006-0170-6
  21. DiMattio J, Hochwald GM, Malhan C, Wald A. Effects of changes in serum osmolarity on bulk flow of fluid into cerebral ventricles and on brain water content. Pflugers Arch 1975;359:253-64. https://doi.org/10.1007/BF00587383
  22. Bering EA Jr, Sato O. Hydrocephalus: changes in formation and absorption of cerebrospinal fluid within the cerebral ventricles. J Neurosurg 1963;20:1050-63. https://doi.org/10.3171/jns.1963.20.12.1050
  23. Milhorat TH, Hammock MK, Fenstermacher JD, Levin VA. Cerebrospinal fluid production by the choroid plexus and brain. Science 1971;173:330-2. https://doi.org/10.1126/science.173.3994.330
  24. Tait MJ, Saadoun S, Bell BA, Papadopoulos MC. Water movements in the brain: role of aquaporins. Trends Neurosci 2008;31:37-43. https://doi.org/10.1016/j.tins.2007.11.003
  25. Strange K. Regulation of solute and water balance and cell volume in the central nervous system. J Am Soc Nephrol 1992;3:12-27.
  26. Kubes P. Nitric oxide modulates epithelial permeability in the feline small intestine. Am J Physiol 1992;262(6 Pt 1):G1138-42.
  27. Janigro D, Leaman SM, Stanness KA. Dynamic modeling of the blood-brain barrier: a novel tool for studies of drug delivery to the brain. Pharm Sci Technolo Today 1999;2:7-12. https://doi.org/10.1016/S1461-5347(98)00110-2
  28. Sivakumar V, Lu J, Ling EA, Kaur C. Vascular endothelial growth factor and nitric oxide production in response to hypoxia in the choroid plexus in neonatal brain. Brain Pathol 2008;18:71-85. https://doi.org/10.1111/j.1750-3639.2007.00104.x
  29. Bloch O, Papadopoulos MC, Manley GT, Verkman AS. Aquaporin-4 gene deletion in mice increases focal edema associated with staphylococcal brain abscess. J Neurochem 2005;95:254-62. https://doi.org/10.1111/j.1471-4159.2005.03362.x
  30. Kiening KL, van Landeghem FK, Schreiber S, Thomale UW, von Deimling A, Unterberg AW, Stover JF. Decreased hemispheric Aquaporin-4 is linked to evolving brain edema following controlled cortical impact injury in rats. Neurosci Lett 2002;324:105-8. https://doi.org/10.1016/S0304-3940(02)00180-5
  31. Ke C, Poon WS, Ng HK, Lai FM, Tang NL, Pang JC. Impact of experimental acute hyponatremia on severe traumatic brain injury in rats: influences on injuries, permeability of blood-brain barrier, ultrastructural features, and aquaporin-4 expression. Exp Neurol 2002;178:194-206. https://doi.org/10.1006/exnr.2002.8037
  32. Nag S, Picard P, Stewart DJ. Increased immunolocalization of nitric oxide synthases during blood-brain barrier breakdown and cerebral edema. Acta Neurochir Suppl 2000;76:65-8.
  33. Mayhan WG. Regulation of blood-brain barrier permeability. Microcirculation 2001;8:89-104.
  34. Qaum T, Xu Q, Joussen AM, Clemens MW, Qin W, Miyamoto K, Hassessian H, Wiegand SJ, Rudge J, Yancopoulos GD, Adamis AP. VEGF-initiated blood-retinal barrier breakdown in early diabetes. Invest Ophthalmol Vis Sci 2001;42:2408-13.
  35. van Bruggen N, Th ibodeaux H, Palmer JT, Lee WP, Fu L, Cairns B, Tumas D, Gerlai R, Williams SP, van Lookeren Campagne M, Ferrara N. VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain. J Clin Invest 1999;104:1613-20. https://doi.org/10.1172/JCI8218
  36. Busse R, Edwards G, Feletou M, Fleming I, Vanhoutte PM, Weston AH. EDHF: bringing the concepts together. Trends Pharmacol Sci 2002;23:374-80. https://doi.org/10.1016/S0165-6147(02)02050-3
  37. Elhusseiny A, Hamel E. Muscarinic--but not nicotinic-- acetylcholine receptors mediate a nitric oxide-dependent dilation in brain cortical arterioles: a possible role for the M5 receptor subtype. J Cereb Blood Flow Metab 2000;20:298-305. https://doi.org/10.1097/00004647-200002000-00011
  38. Faraci FM, Heistad DD. Regulation of the cerebral circulation: role of endothelium and potassium channels. Physiol Rev 1998;78:53-97. https://doi.org/10.1152/physrev.1998.78.1.53
  39. Zhang ZG, Reif D, Macdonald J, Tang WX, Kamp DK, Gentile RJ, Shakespeare WC, Murray RJ, Chopp M. ARL 17477, a potent and selective neuronal NOS inhibitor decreases infarct volume after transient middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab 1996;16:599-604. https://doi.org/10.1097/00004647-199607000-00009
  40. Veltkamp R, Rajapakse N, Robins G, Puskar M, Shimizu K, Busija D. Transient focal ischemia increases endothelial nitric oxide synthase in cerebral blood vessels. Stroke 2002;33:2704-10. https://doi.org/10.1161/01.STR.0000033132.85123.6A
  41. Szpak GM, Lechowicz W, Lewandowska E, Bertrand E, Wierzba- Bobrowicz T, Dymecki J. Border zone neovascularization in cerebral ischemic infarct. Folia Neuropathol 1999;37:264-8.
  42. Marti HJ, Bernaudin M, Bellail A, Schoch H, Euler M, Petit E, Risau W. Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol 2000;156:965-76. https://doi.org/10.1016/S0002-9440(10)64964-4
  43. Han F, Shirasaki Y, Fukunaga K. Microsphere embolism-induced endothelial nitric oxide synthase expression mediates disruption of the blood-brain barrier in rat brain. J Neurochem 2006;99:97-106. https://doi.org/10.1111/j.1471-4159.2006.04048.x
  44. Heo JH, Han SW, Lee SK. Free radicals as triggers of brain edema formation after stroke. Free Radic Biol Med 2005;39:51-70. https://doi.org/10.1016/j.freeradbiomed.2005.03.035
  45. Rosenberg GA, Yang Y. Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia. Neurosurg Focus 2007;22:E4.
  46. Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC, Lipton SA. S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 2002;297:1186-90. https://doi.org/10.1126/science.1073634
  47. Melani A, Turchi D, Vannucchi MG, Cipriani S, Gianfriddo M, Pedata F. ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia. Neurochem Int 2005;47:442-8. https://doi.org/10.1016/j.neuint.2005.05.014
  48. Windmuller O, Lindauer U, Foddis M, Einhaupl KM, Dirnagl U, Heinemann U, Dreier JP. Ion changes in spreading ischaemia induce rat middle cerebral artery constriction in the absence of NO. Brain 2005;128(Pt 9):2042-51. https://doi.org/10.1093/brain/awh545
  49. Johanson CE, Palm DE, Primiano MJ, McMillan PN, Chan P, Knuckey NW, Stopa EG. Choroid plexus recovery after transient forebrain ischemia: role of growth factors and other repair mechanisms. Cell Mol Neurobiol 2000;20:197-216. https://doi.org/10.1023/A:1007097622590

Cited by

  1. Overexpression of aquaporin-1 aggravates hippocampal damage in mouse traumatic brain injury models vol.9, pp.3, 2014, https://doi.org/10.3892/mmr.2014.1899
  2. Effect of 10 different polymorphisms on preoperative volumetric characteristics of glioblastoma multiforme vol.126, pp.3, 2011, https://doi.org/10.1007/s11060-015-2005-9
  3. The Choroid Plexus in Healthy and Diseased Brain vol.75, pp.3, 2016, https://doi.org/10.1093/jnen/nlv030
  4. Interleukin-1β induces the upregulation of caveolin-1 expression in a rat brain tumor model vol.4, pp.4, 2011, https://doi.org/10.3892/br.2016.618
  5. miR-320a affects spinal cord edema through negatively regulating aquaporin-1 of blood–spinal cord barrier during bimodal stage after ischemia reperfusion injury in rats vol.17, pp.None, 2011, https://doi.org/10.1186/s12868-016-0243-1
  6. The Dual Role of AQP4 in Cytotoxic and Vasogenic Edema Following Spinal Cord Contusion and Its Possible Association With Energy Metabolism via COX5A vol.13, pp.None, 2019, https://doi.org/10.3389/fnins.2019.00584
  7. Inhaled gold nanoparticles cause cerebral edema and upregulate endothelial aquaporin 1 expression, involving caveolin 1 dependent repression of extracellular regulated protein kinase activity vol.16, pp.None, 2011, https://doi.org/10.1186/s12989-019-0324-2
  8. General Study and Gene Expression Profiling of Endotheliocytes Cultivated on Electrospun Materials vol.12, pp.24, 2019, https://doi.org/10.3390/ma12244082
  9. Increased oxidative stress and cancer biomarkers in the ventral prostate of older rats submitted to maternal malnutrition vol.523, pp.None, 2021, https://doi.org/10.1016/j.mce.2020.111148
  10. Aquaporins in platelet function vol.32, pp.7, 2011, https://doi.org/10.1080/09537104.2021.1904133
  11. Neurofluids—Deep inspiration, cilia and preloading of the astrocytic network vol.99, pp.11, 2011, https://doi.org/10.1002/jnr.24935