Skip to main content

Advertisement

SpringerLink
Log in

Posterior Reversible Encephalopathy Syndrome After Transplantation: a Review

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disease. Recently, an increase in the number of transplantations has led to more cases being associated with PRES than what was previously reported. Calcineurin inhibitors (CNIs) are major risk factors for PRES in posttransplantation patients. The mechanisms of the development of PRES remain to be unclear. The typical clinical symptoms of PRES include seizures, acute encephalopathy syndrome, and visual symptoms. The hyperintense signal on fluid-attenuated inversion recovery image is the characteristic of the imaging appearance in these patients. In addition, other abnormal signals distributed in multiple locations are also reported in some atypical cases. Unfortunately, PRES is often not recognized or diagnosed too late due to complicated differential diagnoses, such as ischemic stroke, progressive multifocal leukoencephalopathy, and neurodegenerative diseases. Thus, this review emphasizes the importance of considering the possibility of PRES when neurological disturbances appear after solid organ transplantation or hematopoietic cell transplantation. Moreover, this review demonstrates the molecular mechanisms of PRES associated with CNIs after transplantation, which aims to help clinicians further understand PRES in the transplantation era.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ACEI:

Angiotensin-converting enzyme inhibitors

ADC:

Apparent diffusion coefficient

CNIs:

Calcineurin inhibitors

CsA:

Cyclosporine A

CSF:

Cerebrospinal fluid

DNA:

Deoxyribonucleic acid

DWI:

Diffusion weighted MRI

EBV:

Epstein–Barr virus

FLAIR:

Fluid-attenuated inversion recovery

HSCT:

Hematopoietic stem cell transplantation

MRI:

Magnetic resonance imaging

ODS:

Osmotic demyelination syndrome

PAI-1:

Plasminogen activator inhibitor-1

PKA:

Protein kinase A

PKC:

Protein kinase C

PRES:

Posterior reversible encephalopathy syndrome

PTLD:

Posttransplantation lymphoproliferative disorder

T1WI:

T1-weighted image

T2WI:

T2-weighted image

TAC:

Tacrolimus

SOT:

Solid organ transplantation

References

  1. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pessin MS, Lamy C et al (1996) A reversible posterior leukoencephalopathy syndrome. N Engl J Med 334:494–500

    Article  CAS  PubMed  Google Scholar 

  2. Bartynski WS (2008) Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 29:1036–1042

    Article  CAS  PubMed  Google Scholar 

  3. Lamy C, Oppenheim C, Mas JL (2014) Posterior reversible encephalopathy syndrome. Handb Clin Neurol 121:1687–1701

    Article  CAS  PubMed  Google Scholar 

  4. Staykov D, Schwab S (2012) Posterior reversible encephalopathy syndrome. J Intensive Care Med 27:11–24

    Article  PubMed  Google Scholar 

  5. Wu Q, Marescaux C, Wolff V, Jeung MY, Kessler R, Lauer V, Chen Y (2010) Tacrolimus-associated posterior reversible encephalopathy syndrome after solid organ transplantation. Eur Neurol 64:169–177

    Article  CAS  PubMed  Google Scholar 

  6. Agildere AM, Basaran C, Cakir B, Ozgul E, Kural F, Haberal M (2006) Evaluation of neurologic complications by brain MRI in kidney and liver transplant recipients. Transplant Proc 38:611–618

    Article  CAS  PubMed  Google Scholar 

  7. McKinney AM, Short J, Truwit CL, McKinney ZJ, Kozak OS, SantaCruz KS, Teksam M (2007) Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol 189:904–912

    Article  PubMed  Google Scholar 

  8. Alexander S, David VG, Varughese S, Tamilarasi V, Jacob CK (2013) Posterior reversible encephalopathy syndrome in a renal allograft recipient: a complication of immunosuppression? Indian J Nephrol 23:137–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Alparslan M, Bora U, Huseyin K, Ayhan D, Gultekin S (2013) Posterior reversible encephalopathy syndrome in a renal transplanted patient. Am J Case Rep 14:241–244

    Article  PubMed  PubMed Central  Google Scholar 

  10. Apuri S, Carlin K, Bass E, Nguyen PT, Greene JN (2014) Tacrolimus associated posterior reversible encephalopathy syndrome—a case series and review. Mediterr J Hematol Infect Dis 6:e2014014

    Article  PubMed  PubMed Central  Google Scholar 

  11. Arimura FE, Camargo PC, Costa AN, Teixeira RH, Carraro RM, Afonso JE Jr, Campos SV, Samano MN et al (2014) Posterior reversible encephalopathy syndrome in lung transplantation: 5 case reports. Transplant Proc 46:1845–1848

    Article  CAS  PubMed  Google Scholar 

  12. Baldini M, Bartolini E, Gori S, Bonanni E, Cosottini M, Iudice A, Murri L (2010) Epilepsy after neuroimaging normalization in a woman with tacrolimus-related posterior reversible encephalopathy syndrome. Epilepsy Behav 17:558–560

    Article  PubMed  Google Scholar 

  13. Barbas AS, Rege AS, Castleberry AW, Gommer J, Ellis MJ, Brennan TV, Collins BH, Martin AE et al (2013) Posterior reversible encephalopathy syndrome independently associated with tacrolimus and sirolimus after multivisceral transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 13:808–810

    Article  CAS  Google Scholar 

  14. Cordelli DM, Masetti R, Bernardi B, Barcia G, Gentile V, Biagi C, Prete A, Pession A et al (2012) Status epilepticus as a main manifestation of posterior reversible encephalopathy syndrome after pediatric hematopoietic stem cell transplantation. Pediatr Blood Cancer 58:785–790

    Article  PubMed  Google Scholar 

  15. Cruz RJ Jr, DiMartini A, Akhavanheidari M, Iacovoni N, Boardman JF, Donaldson J, Humar A, Bartynski WS (2012) Posterior reversible encephalopathy syndrome in liver transplant patients: clinical presentation, risk factors and initial management. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 12:2228–2236

    Article  Google Scholar 

  16. Fukuyama T, Tanaka M, Nakazawa Y, Motoki N, Inaba Y, Higuchi T, Koike K (2011) Prophylactic treatment for hypertension and seizure in a case of allogeneic hematopoietic stem cell transplantation after posterior reversible encephalopathy syndrome. Pediatr Transplant 15:E169–E173

    Article  CAS  PubMed  Google Scholar 

  17. Hammerstrom AE, Howell J, Gulbis A, Rondon G, Champlin RE, Popat U (2013) Tacrolimus-associated posterior reversible encephalopathy syndrome in hematopoietic allogeneic stem cell transplantation. Am J Hematol 88:301–305

    Article  CAS  PubMed  Google Scholar 

  18. Hayes D Jr, Adler B, Turner TL, Mansour HM (2014) Alternative tacrolimus and sirolimus regimen associated with rapid resolution of posterior reversible encephalopathy syndrome after lung transplantation. Pediatr Neurol 50:272–275

    Article  PubMed  Google Scholar 

  19. Heo S, Cho HJ, Jeon IS (2010) A case of posterior reversible encephalopathy syndrome in a child with myelodysplastic syndrome following allogenic bone marrow transplantation. Pediatr Hematol Oncol 27:59–64

    Article  CAS  PubMed  Google Scholar 

  20. Jennane S, el Mahtat M, Konopacki J, Malfuson JV, Doghmi K, Mikdame M, De Revel T (2013) Cyclosporine-related posterior reversible encephalopathy syndrome after cord blood stem cell transplantation. Hematol Oncol Stem Cell Ther 6:71

    Article  PubMed  Google Scholar 

  21. Loar RW, Patterson MC, O’Leary PW, Driscoll DJ, Johnson JN (2013) Posterior reversible encephalopathy syndrome and hemorrhage associated with tacrolimus in a pediatric heart transplantation recipient. Pediatr Transplant 17:E67–E70

    Article  PubMed  Google Scholar 

  22. Moris D, Vernadakis S, Lionaki S, Daikos G, Zavos G (2014) An uncommon cause of acutely altered mental status in a renal transplant recipient. Ups J Med Sci 119:50–54

    Article  PubMed  PubMed Central  Google Scholar 

  23. Qin W, Tan CY, Huang X, Huang Z, Tao Y, Fu P (2011) Rapamycin-induced posterior reversible encephalopathy in a kidney transplantation patient. Int Urol Nephrol 43:913–916

    Article  PubMed  Google Scholar 

  24. Rosso L, Nosotti M, Mendogni P, Palleschi A, Tosi D, Montoli M, Pappalettera M, Tarsia P et al (2012) Lung transplantation and posterior reversible encephalopathy syndrome: a case series. Transplant Proc 44:2022–2025

    Article  CAS  PubMed  Google Scholar 

  25. Santos MM, Tannuri AC, Gibelli NE, Ayoub AA, Maksoud-Filho JG, Andrade WC, Velhote MC, Silva MM et al (2011) Posterior reversible encephalopathy syndrome after liver transplantation in children: a rare complication related to calcineurin inhibitor effects. Pediatr Transplant 15:157–160

    PubMed  Google Scholar 

  26. Shao X, He Z, Tang L, Gao L (2012) Tacrolimus-associated ischemic optic neuropathy and posterior reversible encephalopathy syndrome after small bowel transplantation. Transplantation 94:e58–e60

    Article  PubMed  Google Scholar 

  27. Shoji T, Bando T, Fujinaga T, Chen F, Kohno M, Yabe M, Yabe H, Date H (2012) Posterior reversible encephalopathy syndrome due to immunosuppressant after living-donor lobar lung transplantation: report of a case. Gen Thorac Cardiovasc Surg 60:514–517

    Article  PubMed  Google Scholar 

  28. Torelli GF, Natalino F, Barberi W, Iori AP, Andreoli C, Valle V, Mercanti C, Perrone S et al (2011) Early onset of posterior reversible encephalopathy syndrome (PRES) during Cyclosporine-A infusion. Leuk Res 35:1423–1424

    Article  PubMed  Google Scholar 

  29. Ueda N, Kawamura M, Nakazawa S, Hirai T, Kishikawa H, Nishimura K (2014) Posterior reversible encephalopathy syndrome (PRES) after kidney transplantation: a case report. Hinyokika Kiyo Acta Urologica Jpn 60:387–392

    Google Scholar 

  30. Yilmaz S, Gokben S, Arikan C, Calli C, Serdaroglu G (2010) Reversibility of cytotoxic edema in tacrolimus leukoencephalopathy. Pediatr Neurol 43:359–362

    Article  PubMed  Google Scholar 

  31. Zaman S R (2012) Posterior reversible encephalopathy syndrome postautologous peripheral stem cell transplantation for multiple myeloma. BMJ Case Rep 2012

  32. Bartynski WS, Tan HP, Boardman JF, Shapiro R, Marsh JW (2008) Posterior reversible encephalopathy syndrome after solid organ transplantation. AJNR Am J Neuroradiol 29:924–930

    Article  CAS  PubMed  Google Scholar 

  33. Wong R, Beguelin GZ, de Lima M, Giralt SA, Hosing C, Ippoliti C, Forman AD, Kumar AJ et al (2003) Tacrolimus-associated posterior reversible encephalopathy syndrome after allogeneic haematopoietic stem cell transplantation. Br J Haematol 122:128–134

    Article  CAS  PubMed  Google Scholar 

  34. Graham BR, Pylypchuk GB (2014) Posterior reversible encephalopathy syndrome in an adult patient undergoing peritoneal dialysis: a case report and literature review. BMC Nephrol 15:10

    Article  PubMed  PubMed Central  Google Scholar 

  35. Nakajima N, Ueda M, Nagayama H, Yamazaki M, Katayama Y (2013) Posterior reversible encephalopathy syndrome due to hypercalcemia associated with parathyroid hormone-related peptide: a case report and review of the literature. Intern Med 52:2465–2468

    Article  PubMed  Google Scholar 

  36. Tsang BK, Kermeen FD, Hopkins PM, Chambers DC (2010) Reversible posterior leukoencephalopathy syndrome: diagnosis and management in the setting of lung transplantation. Int Med J 40:716–720

    Article  CAS  Google Scholar 

  37. Rabinstein AA, Mandrekar J, Merrell R, Kozak OS, Durosaro O, Fugate JE (2012) Blood pressure fluctuations in posterior reversible encephalopathy syndrome. J Stroke Cerebrovasc Dis Off J Natl Stroke Assoc 21:254–258

    Article  Google Scholar 

  38. Fugate JE, Claassen DO, Cloft HJ, Kallmes DF, Kozak OS, Rabinstein AA (2010) Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings. Mayo Clin Proc 85:427–432

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hefzy HM, Bartynski WS, Boardman JF, Lacomis D (2009) Hemorrhage in posterior reversible encephalopathy syndrome: imaging and clinical features. AJNR Am J Neuroradiol 30:1371–1379

    Article  CAS  PubMed  Google Scholar 

  40. Araz C, Camkiran A, Zeyneloglu P, Sezgin A, Moray G, Pirat A, Arslan G (2013) Early-onset posterior reversible encephalopathy syndrome after solid organ transplantation in pediatric patients: a report of 2 cases. Transplant Proc 45:3555–3557

    Article  CAS  PubMed  Google Scholar 

  41. Hugonnet E, Da Ines D, Boby H, Claise B, Petitcolin V, Lannareix V, Garcier JM (2013) Posterior reversible encephalopathy syndrome (PRES): features on CT and MR imaging. Diagn Interv Imaging 94:45–52

    Article  CAS  PubMed  Google Scholar 

  42. Zivkovic SA (2013) Neurologic complications after liver transplantation. World J Hepatol 5:409–416

    Article  PubMed  PubMed Central  Google Scholar 

  43. Stevens CJ, Heran MK (2012) The many faces of posterior reversible encephalopathy syndrome. Br J Radiol 85:1566–1575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. King JD, Rosner MH (2010) Osmotic demyelination syndrome. Am J Medi Sci 339:561–567

    Article  Google Scholar 

  45. de Souza A (2013) Movement disorders and the osmotic demyelination syndrome. Parkinsonism Relat Disord 19:709–716

    Article  PubMed  Google Scholar 

  46. Alleman AM (2014) Osmotic demyelination syndrome: central pontine myelinolysis and extrapontine myelinolysis. Semin Ultrasound CT MR 35:153–159

    Article  PubMed  Google Scholar 

  47. Lake W, Chang JE, Kennedy T, Morgan A, Salamat S, Baskaya MK (2013) A case series of primary central nervous system posttransplantation lymphoproliferative disorder: imaging and clinical characteristics. Neurosurgery 72:960–970, discussion 970

    Article  PubMed  PubMed Central  Google Scholar 

  48. Vegso G, Hajdu M, Sebestyen A (2011) Lymphoproliferative disorders after solid organ transplantation-classification, incidence, risk factors, early detection and treatment options. Pathol Oncol Res 17:443–454

    Article  PubMed  Google Scholar 

  49. Pruitt AA, Graus F, Rosenfeld MR (2013) Neurological complications of solid organ transplantation. Neurohospitalist 3:152–166

    Article  PubMed  PubMed Central  Google Scholar 

  50. Fung JJ, Alessiani M, Abu-Elmagd K, Todo S, Shapiro R, Tzakis A, Van Thiel D, Armitage J et al (1991) Adverse effects associated with the use of FK 506. Transplant Proc 23:3105–3108

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Hewer E, Kellner-Weldon F, Abu-Isa J, Schmitt AM (2014) Multiple cerebral lesions in a 60-year-old female patient with a history of liver transplantation. Neuropathol Off J Jpn Soc Neuropathol 34:425–427

    Google Scholar 

  52. Meriden Z, Bullock GC, Bagg A, Bonatti H, Cousar JB, Lopes MB, Robbins MK, Cathro HP (2010) Posttransplantation lymphoproliferative disease involving the pituitary gland. Hum Pathol 41:1641–1645

    Article  CAS  PubMed  Google Scholar 

  53. Baehring JM, Landry ML, Cooper D, Hui P, Bannykh S (2008) CSF IgH gene rearrangement analysis in isolated post-transplant lymphoproliferative disorder of the central nervous system. J Neuro-Oncol 86:57–60

    Article  Google Scholar 

  54. Shah R, Bag AK, Chapman PR, Cure JK (2010) Imaging manifestations of progressive multifocal leukoencephalopathy. Clin Radiol 65:431–439

    Article  CAS  PubMed  Google Scholar 

  55. Sahraian MA, Radue EW, Eshaghi A, Besliu S, Minagar A (2012) Progressive multifocal leukoencephalopathy: a review of the neuroimaging features and differential diagnosis. Eur J Neurol Off J Eur Fed Neurol Soc 19:1060–1069

    CAS  Google Scholar 

  56. Horger M, Beschorner R, Beck R, Nagele T, Schulze M, Ernemann U, Heckl S (2012) Common and uncommon imaging findings in progressive multifocal leukoencephalopathy (PML) with differential diagnostic considerations. Clin Neurol Neurosurg 114:1123–1130

    Article  CAS  PubMed  Google Scholar 

  57. Pruitt AA, Graus F, Rosenfeld MR (2013) Neurological complications of transplantation: part I: hematopoietic cell transplantation. Neurohospitalist 3:24–38

    Article  PubMed  PubMed Central  Google Scholar 

  58. Weissert R (2011) Progressive multifocal leukoencephalopathy. J Neuroimmunol 231:73–77

    Article  CAS  PubMed  Google Scholar 

  59. Stott VL, Hurrell MA, Anderson TJ (2005) Reversible posterior leukoencephalopathy syndrome: a misnomer reviewed. Int Med J 35:83–90

    Article  CAS  Google Scholar 

  60. Dzudie A, Boissonnat P, Roussoulieres A, Cakmak, Mosbah K, Bejui FT, Obadia JF, Sebbag L (2009) Cyclosporine-related posterior reversible encephalopathy syndrome after heart transplantation: should we withdraw or reduce cyclosporine?: case reports. Transplant Proc 41:716–720

    Article  CAS  PubMed  Google Scholar 

  61. Munoz R, Espinoza M, Espinoza O, Andrade A, Bravo E, Gonzalez F (2006) Cyclosporine-associated leukoencephalopathy in organ transplant recipients: experience of three clinical cases. Transplant Proc 38:921–923

    Article  CAS  PubMed  Google Scholar 

  62. Heidenhain C, Puhl G, Neuhaus P (2009) Late fulminant posterior reversible encephalopathy syndrome after liver transplant. Exp Clin Transplant Off J Middle East Soc Organ Transplant 7:180–183

    Google Scholar 

  63. Schmidt D, Schachter SC (2014) Drug treatment of epilepsy in adults. BMJ 348:g254

    Article  PubMed  Google Scholar 

  64. Ruiz-Gimenez J, Sanchez-Alvarez JC, Canadillas-Hidalgo F, Serrano-Castro PJ, Andalusian Epilepsy S (2010) Antiepileptic treatment in patients with epilepsy and other comorbidities. Seizure 19:375–382

    Article  CAS  PubMed  Google Scholar 

  65. Aronow WS, Fleg JL, Pepine CJ, Artinian NT, Bakris G, Brown AS, Ferdinand KC, Ann Forciea M et al (2011) ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Soc Hypertens 5:259–352

    Article  PubMed  Google Scholar 

  66. Price RS, Kasner SE (2014) Hypertension and hypertensive encephalopathy. Handb Clin Neurol 119:161–167

    Article  PubMed  Google Scholar 

  67. Roth C, Ferbert A (2010) Posterior reversible encephalopathy syndrome: long-term follow-up. J Neurol Neurosurg Psychiatry 81:773–777

    Article  PubMed  Google Scholar 

  68. Siegal D, Keller A, Xu W, Bhuta S, Kim DH, Kuruvilla J, Lipton JH, Messner H et al (2007) Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations, and clinical significance. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 13:1369–1379

    Article  Google Scholar 

  69. Prasad N, Gulati S, Gupta RK, Kumar R, Sharma K, Sharma RK (2003) Is reversible posterior leukoencephalopathy with severe hypertension completely reversible in all patients? Pediatr Nephrol 18:1161–1166

    Article  PubMed  Google Scholar 

  70. Bartynski WS (2008) Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. AJNR Am J Neuroradiol 29:1043–1049

    Article  CAS  PubMed  Google Scholar 

  71. Dineen RA, Sibtain N, Karani JB, Lenthall RK (2008) Cerebral manifestations in liver disease and transplantation. Clin Radiol 63:586–599

    Article  CAS  PubMed  Google Scholar 

  72. Spencer CM, Goa KL, Gillis JC (1997) Tacrolimus. An update of its pharmacology and clinical efficacy in the management of organ transplantation. Drugs 54:925–975

    Article  CAS  PubMed  Google Scholar 

  73. Gerard M, Deleersnijder A, Demeulemeester J, Debyser Z, Baekelandt V (2011) Unraveling the role of peptidyl-prolyl isomerases in neurodegeneration. Mol Neurobiol 44:13–27

    Article  CAS  PubMed  Google Scholar 

  74. Ho S, Clipstone N, Timmermann L, Northrop J, Graef I, Fiorentino D, Nourse J, Crabtree GR (1996) The mechanism of action of cyclosporin A and FK506. Clin Immunol Immunopathol 80:S40–S45

    Article  CAS  PubMed  Google Scholar 

  75. Plosker GL, Foster RH (2000) Tacrolimus: a further update of its pharmacology and therapeutic use in the management of organ transplantation. Drugs 59:323–389

    Article  CAS  PubMed  Google Scholar 

  76. Schreiber SL, Crabtree GR (1992) The mechanism of action of cyclosporin A and FK506. Immunol Today 13:136–142

    Article  CAS  PubMed  Google Scholar 

  77. Dohgu S, Yamauchi A, Nakagawa S, Takata F, Kai M, Egawa T, Naito M, Tsuruo T et al (2004) Nitric oxide mediates cyclosporine-induced impairment of the blood–brain barrier in cocultures of mouse brain endothelial cells and rat astrocytes. Eur J Pharmacol 505:51–59

    Article  CAS  PubMed  Google Scholar 

  78. Kochi S, Takanaga H, Matsuo H, Naito M, Tsuruo T, Sawada Y (1999) Effect of cyclosporin A or tacrolimus on the function of blood–brain barrier cells. Eur J Pharmacol 372:287–295

    Article  CAS  PubMed  Google Scholar 

  79. Kochi S, Takanaga H, Matsuo H, Ohtani H, Naito M, Tsuruo T, Sawada Y (2000) Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus. Life Sci 66:2255–2260

    Article  CAS  PubMed  Google Scholar 

  80. Ozawa T (2008) Effects of FK506 on ca release channels (review). Perspect Med Chem 2:51–55

    CAS  Google Scholar 

  81. Wang J, Guo R, Liu S, Chen Q, Zuo S, Yang M, Zuo X (2014) Molecular mechanisms of FK506-induced hypertension in solid organ transplantation patients. Chin Med J 127:3645–3650

    PubMed  Google Scholar 

  82. Cameron AM, Steiner JP, Roskams AJ, Ali SM, Ronnett GV, Snyder SH (1995) Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12 complex modulates Ca2+ flux. Cell 83:463–472

    Article  CAS  PubMed  Google Scholar 

  83. Gold BG (1997) FK506 and the role of immunophilins in nerve regeneration. Mol Neurobiol 15:285–306

    Article  CAS  PubMed  Google Scholar 

  84. Abbott NJ, Revest PA (1991) Control of brain endothelial permeability. Cerebrovasc Brain Metab Rev 3:39–72

    CAS  PubMed  Google Scholar 

  85. De Bock M, Wang N, Decrock E, Bol M, Gadicherla AK, Culot M, Cecchelli R, Bultynck G et al (2013) Endothelial calcium dynamics, connexin channels and blood–brain barrier function. Prog Neurobiol 108:1–20

    Article  PubMed  CAS  Google Scholar 

  86. Hawkins BT, Davis TP (2005) The blood–brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57:173–185

    Article  CAS  PubMed  Google Scholar 

  87. Huber JD, Egleton RD, Davis TP (2001) Molecular physiology and pathophysiology of tight junctions in the blood–brain barrier. Trends Neurosci 24:719–725

    Article  CAS  PubMed  Google Scholar 

  88. Stuart RO, Sun A, Bush KT, Nigam SK (1996) Dependence of epithelial intercellular junction biogenesis on thapsigargin-sensitive intracellular calcium stores. J Biol Chem 271:13636–13641

    Article  CAS  PubMed  Google Scholar 

  89. Dohgu S, Sumi N, Nishioku T, Takata F, Watanabe T, Naito M, Shuto H, Yamauchi A et al (2010) Cyclosporin A induces hyperpermeability of the blood–brain barrier by inhibiting autocrine adrenomedullin-mediated up-regulation of endothelial barrier function. Eur J Pharmacol 644:5–9

    Article  CAS  PubMed  Google Scholar 

  90. Fernandes S, Salta S, Bravo J, Silva A P, Summavielle T (2014). Acetyl-L-carnitine prevents methamphetamine-induced structural damage on endothelial cells via ILK-related MMP-9 activity. Mol Neurobiol

  91. Ishizaki T, Chiba H, Kojima T, Fujibe M, Soma T, Miyajima H, Nagasawa K, Wada I et al (2003) Cyclic AMP induces phosphorylation of claudin-5 immunoprecipitates and expression of claudin-5 gene in blood–brain-barrier endothelial cells via protein kinase A-dependent and -independent pathways. Exp Cell Res 290:275–288

    Article  CAS  PubMed  Google Scholar 

  92. Dohgu S, Takata F, Matsumoto J, Oda M, Harada E, Watanabe T, Nishioku T, Shuto H et al (2011) Autocrine and paracrine up-regulation of blood–brain barrier function by plasminogen activator inhibitor-1. Microvasc Res 81:103–107

    Article  CAS  PubMed  Google Scholar 

  93. Juhan-Vague I, Alessi MC, Mavri A, Morange PE (2003) Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk. J Thromb Haemost 1:1575–1579

    Article  CAS  PubMed  Google Scholar 

  94. Ko HM, Lee SH, Kim KC, Joo SH, Choi WS, Shin CY (2015) The role of TLR4 and Fyn interaction on lipopolysaccharide-stimulated PAI-1 expression in astrocytes. Mol Neurobiol 52:8–25

    Article  CAS  PubMed  Google Scholar 

  95. Dohgu S, Kataoka Y, Ikesue H, Naito M, Tsuruo T, Oishi R, Sawada Y (2000) Involvement of glial cells in cyclosporine-increased permeability of brain endothelial cells. Cell Mol Neurobiol 20:781–786

    Article  CAS  PubMed  Google Scholar 

  96. Takata F, Dohgu S, Yamauchi A, Sumi N, Nakagawa S, Naito M, Tsuruo T, Shuto H et al (2007) Inhibition of transforming growth factor-beta production in brain pericytes contributes to cyclosporin A-induced dysfunction of the blood–brain barrier. Cell Mol Neurobiol 27:317–328

    Article  CAS  PubMed  Google Scholar 

  97. Muzi M, Mankoff DA, Link JM, Shoner S, Collier AC, Sasongko L, Unadkat JD (2009) Imaging of cyclosporine inhibition of P-glycoprotein activity using 11C-verapamil in the brain: studies of healthy humans. J Nucl Med Off Publ Soc Nucl Med 50:1267–1275

    CAS  Google Scholar 

  98. Gurkan A, Emingil G, Oktem G, Selvi N, Afacan B, Tunc I, Toz H, Atilla G (2009) Immunohistochemical analysis of inducible and endothelial forms of nitric oxide synthase in cyclosporin A-induced gingival overgrowth. J Periodontol 80:1638–1647

    Article  CAS  PubMed  Google Scholar 

  99. Papachristou E, Papadimitropoulos A, Kotsantis P, Goumenos DS, Katsoris PG, Vlachojannis JG (2010) Interaction of endothelin-1 and nitric oxide pathways in human tubular epithelial cells under the influence of cyclosporine-A. Ren Fail 32:727–732

    Article  CAS  PubMed  Google Scholar 

  100. Ramzy D, Rao V, Tumiati LC, Xu N, Miriuka S, Delgado D, Ross HJ (2006) Role of endothelin-1 and nitric oxide bioavailability in transplant-related vascular injury: comparative effects of rapamycin and cyclosporine. Circulation 114:I214–I219

    PubMed  Google Scholar 

  101. Yang L, Yang XC, Yang JK, Guo YH, Yi FF, Fan Q, Liu XL (2008) Cyclosporin A suppresses proliferation of endothelial progenitor cells: involvement of nitric oxide synthase inhibition. Intern Med 47:1457–1464

    Article  PubMed  Google Scholar 

  102. Minguillon J, Morancho B, Kim SJ, Lopez-Botet M, Aramburu J (2005) Concentrations of cyclosporin A and FK506 that inhibit IL-2 induction in human T cells do not affect TGF-beta1 biosynthesis, whereas higher doses of cyclosporin A trigger apoptosis and release of preformed TGF-beta1. J Leukoc Biol 77:748–758

    Article  CAS  PubMed  Google Scholar 

  103. Kalayci R, Kaya M, Uzun H, Bilgic B, Ahishali B, Arican N, Elmas I, Kucuk M (2009) Influence of hypercholesterolemia and hypertension on the integrity of the blood–brain barrier in rats. Int J Neurosci 119:1881–1904

    Article  CAS  PubMed  Google Scholar 

  104. Mayhan WG (1995) Role of nitric oxide in disruption of the blood–brain barrier during acute hypertension. Brain Res 686:99–103

    Article  CAS  PubMed  Google Scholar 

  105. Mohammadi MT, Shid Moosavi SM, Dehghani GA (2011) Contribution of nitric oxide synthase (NOS) activity in blood–brain barrier disruption and edema after acute ischemia/reperfusion in aortic coarctation-induced hypertensive rats. Iran Biomed J 15:22–30

    PubMed  PubMed Central  Google Scholar 

  106. Nukhet Turkel A, Ziya Ziylan Y (2004) Protection of blood–brain barrier breakdown by nifedipine in adrenaline-induced acute hypertension. Int J Neurosci 114:517–528

    Article  CAS  PubMed  Google Scholar 

  107. Pires PW, Dams Ramos CM, Matin N, Dorrance AM (2013) The effects of hypertension on the cerebral circulation. Am J Physiol Heart Circ Physiol 304:H1598–H1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Poulet R, Gentile MT, Vecchione C, Distaso M, Aretini A, Fratta L, Russo G, Echart C et al (2006) Acute hypertension induces oxidative stress in brain tissues. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 26:253–262

    Article  CAS  Google Scholar 

  109. Mohammadi MT, Dehghani GA (2014) Acute hypertension induces brain injury and blood–brain barrier disruption through reduction of claudins mRNA expression in rat. Pathol Res Pract 210:985–990

    Article  CAS  PubMed  Google Scholar 

  110. Wilasrusmee C, Da Silva M, Siddiqui J, Bruch D, Kittur S, Wilasrusmee S, Kittur DS (2003) Role of endothelin-1 in microvascular dysfunction caused by cyclosporin A. J Am Coll Surg 196:584–591

    Article  PubMed  Google Scholar 

  111. Cauduro RL, Costa C, Lhulier F, Garcia RG, Cabral RD, Goncalves LF, Manfro RC (2005) Endothelin-1 plasma levels and hypertension in cyclosporine-treated renal transplant patients. Clin Transpl 19:470–474

    Article  Google Scholar 

  112. Arii T, Kamiya T, Arii K, Ueda M, Nito C, Katsura KI, Katayama Y (2001) Neuroprotective effect of immunosuppressant FK506 in transient focal ischemia in rat: therapeutic time window for FK506 in transient focal ischemia. Neurol Res 23:755–760

    Article  CAS  PubMed  Google Scholar 

  113. Kumar P, Kalonia H, Kumar A (2010) Possible nitric oxide modulation in protective effect of FK-506 against 3-nitropropionic acid-induced behavioral, oxidative, neurochemical, and mitochondrial alterations in rat brain. Drug Chem Toxicol 33:377–392

    Article  CAS  PubMed  Google Scholar 

  114. Toung TJ, Bhardwaj A, Dawson VL, Dawson TM, Traystman RJ, Hurn PD (1999) Neuroprotective FK506 does not alter in vivo nitric oxide production during ischemia and early reperfusion in rats. Stroke J Cereb Circ 30:1279–1285

    Article  CAS  Google Scholar 

  115. Boger RH (2007) The pharmacodynamics of L-arginine. J Nutr 137:1650S–1655S

    PubMed  Google Scholar 

  116. Puschel A, Lindenblatt N, Katzfuss J, Vollmar B, Klar E (2012) Immunosuppressants accelerate microvascular thrombus formation in vivo: role of endothelial cell activation. Surgery 151:26–36

    Article  PubMed  Google Scholar 

  117. Chiasson VL, Quinn MA, Young KJ, Mitchell BM (2011) Protein kinase CbetaII-mediated phosphorylation of endothelial nitric oxide synthase threonine 495 mediates the endothelial dysfunction induced by FK506 (tacrolimus). J Pharmacol Exp Ther 337:718–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Agrawal S, Dixit A, Singh A, Tripathi P, Singh D, Patel DK, Singh MP (2015) Cyclosporine A and MnTMPyP alleviate alpha-synuclein expression and aggregation in cypermethrin-induced Parkinsonism. Mol Neurobiol 52:1619–1628

    Article  CAS  PubMed  Google Scholar 

  119. Gottschalk S, Cummins CL, Leibfritz D, Christians U, Benet LZ, Serkova NJ (2011) Age and sex differences in the effects of the immunosuppressants cyclosporine, sirolimus and everolimus on rat brain metabolism. Neurotoxicology 32:50–57

    Article  CAS  PubMed  Google Scholar 

  120. Serkova NJ, Christians U, Benet LZ (2004) Biochemical mechanisms of cyclosporine neurotoxicity. Mol Interv 4:97–107

    Article  CAS  PubMed  Google Scholar 

  121. Dohgu S, Nishioku T, Sumi N, Takata F, Nakagawa S, Naito M, Tsuruo T, Yamauchi A et al (2007) Adverse effect of cyclosporin A on barrier functions of cerebral microvascular endothelial cells after hypoxia-reoxygenation damage in vitro. Cell Mol Neurobiol 27:889–899

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China

      Sheng Chen, Jun Hu, Liang Xu, Jun Yu & Jianmin Zhang

    2. Brain Research Institute, Zhejiang University, Hangzhou, Zhejiang, China

      Sheng Chen, Jun Hu, Liang Xu, Jun Yu & Jianmin Zhang

    3. Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA

      Dixon Brandon

    4. Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, Zhejiang, China

      Jianmin Zhang

    Authors
    1. Sheng Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Jun Hu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Liang Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Dixon Brandon
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Jun Yu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Jianmin Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Jun Yu.

    Additional information

    Sheng Chen and Jun Hu contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Chen, S., Hu, J., Xu, L. et al. Posterior Reversible Encephalopathy Syndrome After Transplantation: a Review. Mol Neurobiol 53, 6897–6909 (2016). https://doi.org/10.1007/s12035-015-9560-0

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12035-015-9560-0

    Keywords

    Search

    Navigation